Neurophysiology: Structure, Function, and Communication of Neurons | Summaries Physiology

12.1 OVERVIEW OF THE NERVOUS SYSTEM

If the body is to maintain homeostasis and function effectively, its trillions of cells

must work together in a coordinated fashion. If each cell behaved without regard to

what others were doing, the result would be physiological chaos and death. We

have two organ systems dedicated to maintaining internal coordination-the

endocrine system, which communicates by means of chemical messengers

(hormones) secreted into the blood, and the nervous system, which employs

electrical and chemical means to send messages very quickly from cell to cell.

The nervous system carries out its coordinating task in three basic steps: (1) It

receives information about changes in the body and external environment and

transmits messages to the central nervous system (CNS). (2) The CNS processes

this information and determines what response, if any, is appropriate to the

circumstances. (3) The CNS issues commands primarily to muscle and gland cells

to carry out such

responses.

The nervous system has two major anatomical subdivisions. The central nervous

system (CNS) consists of the brain and spinal cord, which are enclosed and

protected by the cranium and vertebral column.

The peripheral nervous system (PNS), consists of all the rest; it is composed of

nerves and ganglia. A nerve is a bundle of nerve fibers (axons) wrapped in fibrous

connective tissue. Nerves emerge from the CNS through foramina of the skull and

vertebral column and carry signals to and from other organs of the body. A

ganglion' (plural, ganglia) is a knotlike swelling in a nerve where the cell bodies of

peripheral neurons are concentrated.

The peripheral nervous system is functionally divided into sensory and motor

divisions, and each of these is further divided into somatic and visceral

subdivisions.

-The sensory (afferent2) division carries signals from various receptors (sense

organs and simple sensory nerve endings) to the CNS. This pathway informs the

CNS of stimuli within and around the body.

-The somatic sensory division carries signals from receptors in the skin, muscles,

bones, and joints.

The visceral sensory division carries signals mainly from the viscera of the thoracic

and abdominal cavities, such as the heart, lungs, stomach, and urinary bladder.

-The motor (efferent*) division carries signals from the CNS mainly to gland and

muscle cells that carry out the body's responses. Cells and organs that respond to

these signals are called effectors.

-The somatic motor division carries signals to the skeletal muscles. This produces

voluntary muscle contractions as well as automatic

reflexes.

-The visceral motor division (autonomic" nervous system, ANS) carries signals to

glands, cardiac muscle, and smooth muscle. We usually have no voluntary control

over these effectors, and the ANS operates at an unconscious level. The

responses of the ANS and its effectors are visceral reflexes. The ANS has two

further divisions:

-The sympathetic division tends to arouse the body for action-for example, by

accelerating the heartbeat and increasing respiratory

airflow-but it inhibits digestion.

-The parasympathetic division tends to have a calming effect-slowing the heartbeat,

for example-but it stimulates digestion.

The foregoing terms may give the impression that we have several nervous

systems-central, peripheral, sensory, motor, somatic, and visceral. These are just

terms of convenience, however. There is only one nervous system, and these

subsystems are interconnected parts of the whole.

12.2 PROPERTIES OF NEURONS

12.2a Universal Properties

The communicative role of the nervous system is carried out by nerve cells, or

neurons. These cells have three fundamental physiological

properties that enable them to communicate with other cells:

1. Excitability. All cells are excitable-that is, they respond to environmental

changes (stimuli). Neurons exhibit this property to the highest

degree.

2. Conductivity. Neurons respond to stimuli by producing electrical signals that are

quickly conducted to other cells at distant locations.

3. Secretion. When the signal reaches the end of a nerve fiber, the neuron

secretes a neurotransmitter that crosses the gap and stimulates the

next cell.

12.2b Functional Classes

There are three general classes of neurons corresponding to the three major

aspects of nervous system function listed earlier:

1) Sensory (afferent) neurons are specialized to detect stimuli such as light, heat,

pressure, and chemicals, and transmit information

about them to the CNS. Such neurons begin in almost every organ of the body and

end in the CNS; the word afferent refers to signal

conduction toward the CNS. Some receptors, such as those for pain and smell, are

themselves neurons. In other cases, such as taste

and hearing, the receptor is a separate cell that communicates directly with a

sensory neuron.

(2) Interneurons lie entirely within the CNS. They receive signals from many other

neurons and carry out the integrative function of the nervous system-that is, they

process, store, and retrieve information and "make decisions" that determine how

the body responds to stimuli. About 90% of our neurons are interneurons. The word

interneuron refers to the fact that they lie between, and interconnect, the incoming

sensory pathways and the outgoing motor pathways of the CNS.

(3) Motor (efferent) neurons send signals predominantly to muscle and gland

cells, the effectors. They are called motor neurons because most of them lead to

muscle cells, and efferent neurons to signify signal conduction away from the CNS.

12.2c Structure of a Neuron

There are several varieties of neurons, but a good starting point for discussion is a

motor neuron of the spinal cord (L fig. 12.4). The

control center of the neuron is the neurosoma," also called the soma, cell body,

or perikaryon.? It has a centrally located nucleus with a large

nucleolus. The cytoplasm contains mitochondria, lysosomes, a Golgi complex,

numerous inclusions, and an extensive rough endoplasmic

reticulum and cytoskeleton. The cytoskeleton consists of a dense mesh of

microtubules and neurofibrils (bundles of actin filaments), which

compartmentalize the rough ER into dark-staining regions called chromatophilic®

substance (L) fig. 12.4e). This is unique to neurons and a

helpful clue to identifying them in tissue sections with mixed cell types. Mature

neurons have no centrioles and cannot undergo any further

mitosis after adolescence. Consequently, neurons that die are usually

irreplaceable; surviving neurons cannot multiply to replace those lost. However,

neurons are unusually long-lived cells, capable of functioning for over a hundred

years.

The major inclusions in the neurosoma are glycogen granules, lipid droplets,

melanin, and a golden brown pigment called lipofuscin" (LIP-

oh-FEW-sin), produced when lysosomes degrade worn-out organelles and other

products. Lipofuscin accumulates with age and pushes the

nucleus to one side of the cell. Lipofuscin granules are also called "wear-and-tear

granules" because they are most abundant in old neurons.

They are also associated with certain degenerative diseases such as macular

degeneration of the eye and amyotrophic lateral sclerosis (ALS)

The somas of most neurons give rise to a few thick processes that branch into a

vast number of dendrites 10-named for their striking

resemblance to the bare branches of a tree in winter. Dendrites are the primary site

for receiving signals from other neurons. Some neurons

have only one dendrite and some have thousands. The more dendrites a neuron

has, the more information it can receive and incorporate

into its decision making. As tangled as the dendrites may seem, they provide

exquisitely precise pathways for the reception and processing of

neural information.

On one side of the neurosoma is a mound called the axon hillock, from which the

axon (nerve fiber) originates. The axon is cylindrical and

relatively unbranched for most of its length, although it may give rise to a few

branches called axon collaterals near the soma, and most axons

branch extensively at their distal end. An axon is specialized for rapid conduction of

nerve signals to points remote from the soma. Its

cytoplasm is called the axoplasm and its membrane the axolemma. A neuron

never has more than one axon, and some neurons have none.

Somas range from 5 to 135 um in diameter, and axons from 1 to 20 um in diameter

and from a few millimeters to more than a meter long.

(In the great blue whale, one nerve cell can be more than 30 m, or 100 ft, long.)

The dimensions of a human neuron are more impressive

when we scale them up to the size of familiar objects. If the soma of a spinal motor

neuron were the size of a tennis ball, its dendrites would

form a dense bushy mass that could fill a 30-seat classroom from floor to ceiling. Its

axon would be up to a mile long but a little narrower

Partial preview of the text

Download Neurophysiology: Structure, Function, and Communication of Neurons and more Summaries Physiology in PDF only on Docsity!

12.1 OVERVIEW OF THE NERVOUS SYSTEM

If the body is to maintain homeostasis and function effectively, its trillions of cells must work together in a coordinated fashion. If each cell behaved without regard to what others were doing, the result would be physiological chaos and death. We have two organ systems dedicated to maintaining internal coordination-the endocrine system , which communicates by means of chemical messengers (hormones) secreted into the blood, and the nervous system, which employs electrical and chemical means to send messages very quickly from cell to cell. The nervous system carries out its coordinating task in three basic steps: (1) It receives information about changes in the body and external environment and transmits messages to the central nervous system (CNS). (2) The CNS processes this information and determines what response, if any, is appropriate to the circumstances. (3) The CNS issues commands primarily to muscle and gland cells to carry out such responses. The nervous system has two major anatomical subdivisions. The central nervous system (CNS) consists of the brain and spinal cord, which are enclosed and protected by the cranium and vertebral column. The peripheral nervous system (PNS), consists of all the rest; it is composed of nerves and ganglia. A nerve is a bundle of nerve fibers (axons) wrapped in fibrous connective tissue. Nerves emerge from the CNS through foramina of the skull and vertebral column and carry signals to and from other organs of the body. A ganglion' (plural, ganglia) is a knotlike swelling in a nerve where the cell bodies of peripheral neurons are concentrated. The peripheral nervous system is functionally divided into sensory and motor divisions, and each of these is further divided into somatic and visceral subdivisions. -The sensory (afferent2) division carries signals from various receptors (sense organs and simple sensory nerve endings) to the CNS. This pathway informs the CNS of stimuli within and around the body. -The somatic sensory division carries signals from receptors in the skin, muscles, bones, and joints. The visceral sensory division carries signals mainly from the viscera of the thoracic and abdominal cavities, such as the heart, lungs, stomach, and urinary bladder. -The motor (efferent*) division carries signals from the CNS mainly to gland and muscle cells that carry out the body's responses. Cells and organs that respond to these signals are called effectors. -The somatic motor division carries signals to the skeletal muscles. This produces voluntary muscle contractions as well as automatic reflexes. -The visceral motor division (autonomic" nervous system, ANS) carries signals to glands, cardiac muscle, and smooth muscle. We usually have no voluntary control over these effectors, and the ANS operates at an unconscious level. The responses of the ANS and its effectors are visceral reflexes. The ANS has two further divisions: -The sympathetic division tends to arouse the body for action-for example, by accelerating the heartbeat and increasing respiratory airflow-but it inhibits digestion. -The parasympathetic division tends to have a calming effect-slowing the heartbeat, for example-but it stimulates digestion. The foregoing terms may give the impression that we have several nervous systems-central, peripheral, sensory, motor, somatic, and visceral. These are just terms of convenience, however. There is only one nervous system, and these subsystems are interconnected parts of the whole. 12.2 PROPERTIES OF NEURONS 12.2a Universal Properties The communicative role of the nervous system is carried out by nerve cells, or neurons. These cells have three fundamental physiological properties that enable them to communicate with other cells:

Excitability. All cells are excitable-that is, they respond to environmental changes (stimuli). Neurons exhibit this property to the highest degree.
Conductivity. Neurons respond to stimuli by producing electrical signals that are quickly conducted to other cells at distant locations.
Secretion. When the signal reaches the end of a nerve fiber, the neuron secretes a neurotransmitter that crosses the gap and stimulates the next cell. 12.2b Functional Classes There are three general classes of neurons corresponding to the three major aspects of nervous system function listed earlier:
1. Sensory (afferent) neurons are specialized to detect stimuli such as light, heat, pressure, and chemicals, and transmit information about them to the CNS. Such neurons begin in almost every organ of the body and end in the CNS; the word afferent refers to signal conduction toward the CNS. Some receptors, such as those for pain and smell, are themselves neurons. In other cases, such as taste and hearing, the receptor is a separate cell that communicates directly with a sensory neuron. (2) Interneurons lie entirely within the CNS. They receive signals from many other neurons and carry out the integrative function of the nervous system-that is, they process, store, and retrieve information and "make decisions" that determine how the body responds to stimuli. About 90% of our neurons are interneurons. The word interneuron refers to the fact that they lie between, and interconnect, the incoming sensory pathways and the outgoing motor pathways of the CNS. (3) Motor (efferent) neurons send signals predominantly to muscle and gland cells, the effectors. They are called motor neurons because most of them lead to muscle cells, and efferent neurons to signify signal conduction away from the CNS. 12.2c Structure of a Neuron There are several varieties of neurons, but a good starting point for discussion is a motor neuron of the spinal cord (L fig. 12.4). The control center of the neuron is the neurosoma ," also called the soma, cell body, or perikaryon .? It has a centrally located nucleus with a large nucleolus. The cytoplasm contains mitochondria, lysosomes, a Golgi complex, numerous inclusions, and an extensive rough endoplasmic reticulum and cytoskeleton. The cytoskeleton consists of a dense mesh of microtubules and neurofibrils (bundles of actin filaments), which compartmentalize the rough ER into dark-staining regions called chromatophilic® substance (L) fig. 12.4e). This is unique to neurons and a helpful clue to identifying them in tissue sections with mixed cell types. Mature neurons have no centrioles and cannot undergo any further mitosis after adolescence. Consequently, neurons that die are usually irreplaceable; surviving neurons cannot multiply to replace those lost. However, neurons are unusually long-lived cells, capable of functioning for over a hundred years. The major inclusions in the neurosoma are glycogen granules, lipid droplets, melanin, and a golden brown pigment called lipofuscin" (LIP- oh-FEW-sin), produced when lysosomes degrade worn-out organelles and other products. Lipofuscin accumulates with age and pushes the nucleus to one side of the cell. Lipofuscin granules are also called "wear-and-tear granules" because they are most abundant in old neurons. They are also associated with certain degenerative diseases such as macular degeneration of the eye and amyotrophic lateral sclerosis (ALS) The somas of most neurons give rise to a few thick processes that branch into a vast number of dendrites 10-named for their striking resemblance to the bare branches of a tree in winter. Dendrites are the primary site for receiving signals from other neurons. Some neurons have only one dendrite and some have thousands. The more dendrites a neuron has, the more information it can receive and incorporate into its decision making. As tangled as the dendrites may seem, they provide exquisitely precise pathways for the reception and processing of neural information. On one side of the neurosoma is a mound called the axon hillock, from which the axon (nerve fiber) originates. The axon is cylindrical and relatively unbranched for most of its length, although it may give rise to a few branches called axon collaterals near the soma, and most axons branch extensively at their distal end. An axon is specialized for rapid conduction of nerve signals to points remote from the soma. Its cytoplasm is called the axoplasm and its membrane the axolemma. A neuron never has more than one axon, and some neurons have none. Somas range from 5 to 135 um in diameter, and axons from 1 to 20 um in diameter and from a few millimeters to more than a meter long. (In the great blue whale, one nerve cell can be more than 30 m, or 100 ft, long.) The dimensions of a human neuron are more impressive when we scale them up to the size of familiar objects. If the soma of a spinal motor neuron were the size of a tennis ball, its dendrites would form a dense bushy mass that could fill a 30-seat classroom from floor to ceiling. Its axon would be up to a mile long but a little narrower

than a garden hose. This is quite a point to ponder. The neuron must assemble molecules and organelles in its "tennis ball" soma and deliver them through its "mile-long garden hose" to the end of the axon. How it achieves this remarkable feat is explained shortly. At the distal end, an axon usually has a terminal arborization - an extensive complex of fine branches. Each branch ends in a bulbous axon terminal (terminal button), which forms a junction (synapse 13) with the next cell. It contains synaptic vesicles full of neurotransmitters. In most autonomic neurons, however, the axon has numerous beads called varicosities along its length (see E) fig. 11.21). Each varicosity contains synaptic vesicles and secretes neurotransmitters. Not all neurons fit the preceding description. Neurons are classified structurally according to the number of processes extending from the soma (L) fig. 12.5):

Multipolar neurons are those, like the preceding, that have one axon and multiple dendrites. This is the most common type and includes most neurons of the brain and spinal cord.
Bipolar neurons have one axon and one dendrite. Examples include olfactory cells of the nose, certain neurons of the retina, and sensory neurons of the ear.
Unipolar neurons have only a single process leading away from the soma. They are represented by the neurons that carry signals to the spinal cord for such senses as touch and pain. They are also called pseudounipolar because they start out as bipolar neurons in the embryo, but their two processes fuse into one as the neuron matures. A short distance away from the soma, the process branches like a T into a peripheral fiber and a central fiber. The peripheral fiber begins with a sensory ending often far away from the soma-in the skin, for example. Its signals travel toward the soma, but bypass it and continue along the central fiber for a short remaining distance to the spinal cord. The dendrites are considered to be only the short receptive endings. The rest of the process, both peripheral and central, is the axon, defined by the presence of myelin and the ability to generate action potentials.
Anaxonic neurons have multiple dendrites but no axon. They communicate locally through their dendrites and do not produce action potentials. Some anaxonic neurons are found in the brain, retina, and adrenal medulla. In the retina, they help in visual processes such as the perception of contrast. 12.2d Axonal Transport All of the proteins needed by a neuron must be made in the soma, where the protein-synthesizing organelles such as the nucleus, ribosomes, and rough endoplasmic reticulum are located. Yet many of these proteins are needed in the axon, for example to repair and maintain the axolemma, to serve as ion channels in the membrane, or to act in the axon terminal as enzymes and signaling molecules. Other substances are transported from the axon terminals back to the soma for disposal or recycling. The two-way passage of proteins, organelles, and other materials along an axon is called axonal transport. Movement away from the soma down the axon is called anterograde 14 transport and movement up the axon toward the soma is called retrograde l5 transport. Materials travel along axonal microtubules that act like monorail tracks to guide them to their destination. But what is the "engine" that drives them along the tracks? Anterograde transport employs a motor protein called kinesin16 and retrograde transport uses one called dyneinI7 (the same protein responsible for the motility of cilia and flagella). These proteins carry materials "on their backs" while they reach out, like the myosin heads of muscle (see L) section 11.4c), to bind repeatedly to the microtubules and walk along them. There are two types of axonal transport: fast and slow.

Fast axonal transport occurs at a rate of 200 to 400 mm/day and may be either anterograde or retrograde: Fast anterograde transport moves mitochondria; synaptic vesicles; other organelles; components of the axolemma; calcium ions; enzymes such as acetylcholinesterase; and small molecules such as glucose, amino acids, and nucleotides toward the distal end of the axon. Fast retrograde transport returns used synaptic vesicles and other materials to the soma and informs the soma of conditions at the axon terminals. Some pathogens exploit this process to invade the nervous system. They enter the distal tips of an axon and travel to the soma by retrograde transport. Examples include tetanus toxin and the herpes simplex, rabies, and polio viruses. In such infections, the delay between infection and the onset of symptoms corresponds to the time needed for the pathogens to reach the somas.
1. Slow axonal transport is an anterograde process that works in a stop-and-go fashion. If we compare fast axonal transport to an express train traveling nonstop to its destination, slow axonal transport is like a local train that stops at every station. When moving, it goes just as fast as the express train, but the frequent stops result in an overall progress of only 0.2 to 0.5 mm/day. It moves enzymes and cytoskeletal components down the axon, renews worn-out axoplasmic components in mature neurons, and supplies new axoplasm for developing or regenerating neurons. Damaged nerves regenerate at a speed governed by slow axonal transport. 12.3 SUPPORTIVE CELLS There are about a trillion (1012) neurons in the nervous system- 10 times as many neurons in your body as there are stars in our galaxy! Because they branch so extensively, they make up about 50% of the volume of the nervous tissue. Yet they are outnumbered at least 10 to 1 by cells called neuroglia (noo-ROG-lee-uh), or glial cells (GLEE-ul). Glial cells protect the neurons and help them function. The word glia, which means "glue," implies one of their roles-to bind neurons together and provide a supportive framework for the nervous tissue. In the fetus, they form a scaffold that guides young migrating neurons to their destinations. Wherever a mature neuron is not in synaptic contact with another cell, it is covered with glial cells. This prevents neurons from contacting each other except at points specialized for signal transmission, thus giving precision to their conduction pathways. 12.3a Types of Neuroglia There are six kinds of neuroglia, each with a unique function (L) table 12.1). The first four types occur only in the central nervous system ( L fig. 12.6):
2. Oligodendrocytes18 (OL-ih-go-DEN-dro-sites) somewhat resemble an octopus; they have a bulbous body with as many as 15 arms. Each arm reaches out to a nerve fiber and spirals around it like electrical tape wrapped repeatedly around a wire. This wrapping, called the myelin sheath, insulates the nerve fiber from the extracellular fluid and speeds up signal conduction in the nerve fiber.
3. EpendymalI9 cells (ep-EN-dih-mul) resemble a cuboidal epithelium lining the internal cavities of the brain and spinal cord. Unlike true epithelial cells, however, they have no basement membrane and they exhibit rootlike processes that penetrate into the underlying tissue Ependymal cells produce cerebrospinal fluid (CSF), a liquid that bathes the CNS and fills its internal cavities. They have patches of cilia on their apical surfaces that help to circulate the SF. Ependymal cells and CSF are considered in more detail in L section 14.2b.
4. Microglia are small macrophages that develop from white blood cells called monocytes. They wander through the CNS, putting out fingerlike extensions to constantly probe the tissue for cellular debris or other problems. They are thought to perform a complete checkup on the brain tissue several times a day, phagocytizing dead tissue, microorganisms, and other foreign matter. They become concentrated in areas damaged by infection, trauma, or stroke. Pathologists look for clusters of microglia in brain tissue as a clue to sites of injury. Microglia also aid in synaptic remodeling, changing the connections between neurons.
5. Astrocytes20 are the most abundant glial cells in the CNS and constitute over 90% of the tissue in some areas of the brain. They cover the entire brain surface and most nonsynaptic regions of the neurons in the gray matter. They are named for their many-branched, somewhat starlike shape. They have the most diverse functions of any glia:
- They form a supportive framework for the nervous tissue.
- They have extensions called perivascular feet, which contact the blood capillaries and stimulate them to form a tight, protective seal called the blood-brain barrier (see L) section 14.2c).
- They monitor neuron activity, stimulate dilation and constriction of blood vessels, and thus regulate blood flow in the brain tissue to meet changing needs for oxygen and nutrients.

(2) When a nerve fiber is cut, the fiber distal to the injury can't survive because it is incapable of protein synthesis. Protein-synthesizing organelles are mostly in the soma. As the distal fiber degenerates, so do its Schwann cells, which depend on it for their maintenance. Macrophages clean up tissue debris at the point of injury and beyond. (3) The soma exhibits a number of abnormalities of its own, probably because it is cut off from the supply of nerve growth factors from the neuron's target cells (see ( Deeper Insight 12.3). The soma swells, the endoplasmic reticulum breaks up (so the chromatophilic substance disperses), and the nucleus moves off center. Not all damaged neurons survive; some die at this stage. But often, the axon stump sprouts multiple growth processes while the severed distal end shows continued degeneration of its axon and Schwann cells. Muscle fibers deprived of their nerve supply exhibit a shrinkage called enervation atrophy. (4) Near the injury, Schwann cells, the basal lamina, and the neurilemma form a regeneration tube. The Schwann cells produce cell- adhesion molecules and nerve growth factors that enable a neuron to regrow to its original destination. When one growth process finds its way into the tube, it grows rapidly (3-5 mm/day), and the other growth processes are retracted. (5) The regeneration tube guides the growing sprout back to the original target cells, reestablishing synaptic contact. (6) When contact is established, the soma shrinks and returns to its original appearance, and the reinnervated muscle fibers regrow. 12.4 ELECTROPHYSIOLOGY OF NEURONS 12.4a Electrical Potentials and Currents Neural communication, like muscle excitation, is based on electrophysiology-cellular mechanisms for producing electrical potentials and currents. An electrical potential is a difference in the concentration of charged particles between one point and another. It is a form of potential energy that, under the right circumstances, can produce a current. An electrical current is a flow of charged particles from one point to another. A new flashlight battery, for example, typically has a potential, or charge, of 1.5 volts (V). If a lightbulb and the two poles of the battery are connected by a wire, electrons flow through the wire from one pole to the other, creating a current that lights the bulb. As long as the battery has a potential (voltage), we say it is polarized. Living cells are also polarized. The charge difference across the plasma membrane is called the resting membrane potential (RMP). It is much less than the potential of a flashlight battery-typically about -70 millivolts (mV) in an unstimulated, "resting" neuron. The negative value means there are more negatively charged particles on the inside of the membrane than on the outside. We don't have free electrons in the body as we do in an electrical circuit. Electrical currents in the body are created, instead, by the flow of ions such as Na* and K* through gated channels in the plasma membrane. Gated channels can be opened and closed by various stimuli, as we have seen earlier (see "Membrane Proteins" in 2 section 3.2a and "Electrically Excitable Cells." @ section 11.3c). This enables cells to turn electrical currents on and off. 12.4b The Resting Membrane Potential The reason a cell has a resting membrane potential is that electrolytes are unequally distributed between the extracellular fluid (ECF) on the outside of the plasma membrane and the intracellular fluid (ICF) on the inside. The MP results from the combined effect of three factors: (1) the diffusion of ions down their concentration gradients through the membrane; (2) selective permeability of the membrane, allowing some ions to pass more easily than others; and (3) the electrical attraction of cations and anions to each other. Potassium ions (K) have the greatest influence on the MP because the plasma membrane is more permeable to K than to any other ion. Imagine a hypothetical cell in which all the K* starts out in the ICF, with none in the ECF. Also in the ICF are a number of cytoplasmic anions that cannot escape from the cell because of their size or charge-phosphates, sulfates, small organic acids, proteins, ATP, and RNA. Potassium ions diffuse freely through leak channels in the plasma membrane, down their concentration gradient and out of the cell, leaving these cytoplasmic anions behind (E) fig. 12.12). As a result, the ICF grows more and more negatively charged. But as the ICF becomes more negative, it exerts a stronger attraction for the positive potassium ions and attracts some of them back into the cell. Eventually an equilibrium is reached in which K* is moving out of the cell (down its concentration gradient) and into the cell (by electrical attraction) at equal rates. There is no further net diffusion of K. At the point of equilibrium. K is about 40 times as concentrated in the ICF as in the ECF If K+ were the only ion affecting the RMP, it would give the membrane a potential of about -90 m V. However, sodium ions (Na) also enter the picture. Sodium is about 12 times as concentrated in the ECF as in the ICF. The resting plasma membrane is much less permeable to Na than to K. but Na does diffuse down its concentration gradient into the cell, attracted by the negative charge in the ICF. This sodium leak is only a trickle, but it is enough to cancel some of the negative charge and reduce the voltage across the membrane. Sodium leaks into the cell and potassium leaks out, but the sodium-potassium (Na-K) pump continually compensates for this leakage. It pumps 3 Na* out of the cell for every 2 K* it brings in, consuming 1 ATP for each exchange cycle (see fig. 3.19). By removing more cations from the cell than it brings in, it contributes about - 3 mV to the RMP. The resting membrane potential of -70 mV is the net effect of all these ion movements-K* diffusion out of the cell, Na* diffusion inward, and the Na-K pump continually offsetting this ion leakage. The Na-K pump accounts for about 70% of the energy (ATP) requirement of the nervous system. Every signal generated by a neuron slightly uses the distribution of K+ and Na+, so the pump must work continually to restore equilibrium. This is why nervous tissue has one of the highest rates of ATP consumption of any tissue in the body, and why it demands so much glucose and oxygen. Although a neuron is said to be resting when it is not producing signals, it is highly active maintaining its RMP and "waiting,as it were, for something to happen. The uneven distribution of Na+ and K* on the two sides of the plasma membrane pertains only to a very thin film of ions immediately adjacent to the membrane surfaces. The electrical events we are about to examine don't involve ions very far away from the membrane in either the ECF or the ICF. 12.4c Local Potentials Stimulation of a neuron causes local disturbances in membrane potential. Typically (but with exceptions), the response begins at a dendrite, spreads through the soma, travels down the axon, and ends at the axon terminal. We consider the process in that order. Various neurons can be stimulated by chemicals, light, heat, or mechanical forces. We'll take as our example a neuron being chemically stimulated (L) fig. 12.13). The chemical (ligand)-perhaps a pain signal from a damaged tissue or odor molecule in a breath of air-binds to receptors on the neuron. This opens ligand-gated sodium channels that allow Na+ to flow into the cell. The Na+ inflow cancels some of the internal negative charge, so the voltage across the membrane at that point drifts toward zero. Any such case in which the voltage shifts to a less negative value is called depolarization. The incoming Na+ diffuses for short distances along the inside of the plasma membrane, creating a wave of excitation that spreads out from the point of stimulation, like ripples spreading across a pond when you drop a stone into it. This short-range change in voltage is called a local potential. There are four characteristics that distinguish local potentials from the action potentials we will study in the next section ( L table 12.2). You will appreciate these distinctions more fully after you have studied action potentials. Local Potential -Produced by gated channels on the dendrites and soma -May be a positive (depolarizing) or negative (hyperpolarizing) voltage change -Graded; proportional to stimulus strength Action Potential -Produced by voltage-gated channels on the trigger zone and axon -Always begins with depolarization -All or none; either does not occur at all or exhibits the same peak voltage regardless of stimulus strength -Irreversible; goes to completion once it begins -Reversible; returns to MP if stimulation ceases before threshold is reached -Local; has effects for only a short distance from point of origin

-Decremental; signal grows weaker with distance -Self-propagating; has effects a great distance from point of origin -Nondecremental; signal maintains same strength regardless of distance

Local potentials are graded, meaning they vary in magnitude (voltage) according to the strength of the stimulus. An intense or prolonged stimulus opens more gated ion channels than a weaker stimulus, and they stay open longer. Thus, more Nat enters the cell and the voltage changes more than it does with a weaker stimulus.
Local potentials are decremental, meaning they get weaker as they spread from the point of origin. They decline in strength partly because the Na* leaks back out of the cell through channels along its path, and partly because as Na" spreads out under the plasma membrane and depolarizes it, K+ flows out and reverses the effect of the Na* inflow. Therefore, the voltage shift caused by Na* diminishes rapidly with distance. This prevents local potentials from having long-distance effects.
Local potentials are reversible, meaning that if stimulation ceases, cation diffusion out of the cell quickly returns the membrane voltage to its resting potential.
Local potentials can be either excitatory or inhibitory. So far, we have considered only excitatory local potentials, which depolarize a cell and make a neuron more likely to produce an action potential. Acetylcholine usually has this effect. Other neurotransmitters, such as glycine, causes an opposite effect-they hyperpolarize a cell, or make the membrane more negative. This inhibits a neuron, making it less sensitive and less likely to produce an action potential. A balance between excitatory and inhibitory potentials is very important to information processing in the nervous system 12.4d Action Potentials An action potential is a more dramatic change produced by voltage-gated ion channels in the plasma membrane. Action potentials occur only where there is a high enough density of voltage-gated channels. Most of the soma has only 50 to 75 channels per square micrometer (um), not dense enough to generate action potentials. The trigger zone, however, has 350 to 500 channels/um. If an excitatory local potential spreads all the way to the trigger zone and is still strong enough when it arrives, it can open these channels and generate an action potential. The action potential is a rapid up-and-down shift in voltage following description.

When the local current arrives at the axon hillock, it depolarizes the membrane at that point. This appears as a steadily rising local potential.
For anything more to happen, this local potential must rise to a critical voltage called the threshold (typically about -55 mV), the minimum needed to open voltage-gated channels.
The neuron now "fires," or produces an action potential. At threshold, voltage-gated Na+ channels open quickly, while gated K+ channels open more slowly. The initial effect on membrane potential is therefore due to Na+. Initially, only a few Na+ channels open, but as Na+ enters the cell, it further depolarizes the membrane. This stimulates still more voltage-gated Nat channels to open and admit even more Na+, a positive feedback loop that causes the membrane voltage to rise even more rapidly.
As the rising potential passes 0 mV, Na+ channels are inactivated and begin closing. By the time they all close and Na+ inflow ceases, the voltage peaks at approximately +35 mV. (The peak is as low as 0 mV in some neurons and as high as 50 mV in others.) The membrane is now positive on the inside and negative on the outside-its polarity is reversed compared to the RMP.
By the time the voltage peaks, the slow K* channels are fully open. Potassium ions, repelled by the positive IC, now exit the cell. Their outflow repolarizes the membrane-that is, it shifts the voltage back into the negative numbers. The action potential consists of the up-and-down voltage shifts that occur from the time the threshold is reached to the time the voltage returns to the RMP.
Potassium channels stay open longer than Na* channels, so slightly more K* leaves the cell than the amount of Na that entered. Therefore, the membrane voltage drops to 1 or 2 mV more negative than the original MP, producing a negative overshoot called hyperpolarization
1. As you can see, Na+ and K+ switch places across the membrane during an action potential. During hyperpolarization, the membrane voltage gradually returns to the MP because of Na diffusion into the cell. Earlier we saw that local potentials are graded, decremental, and reversible. We can now contrast this with action potentials. Action potentials follow an all-or-none law. If a stimulus depolarizes the neuron to threshold, the neuron fires at its maximum voltage (such as +35 mV); if threshold is not reached, the neuron doesn't fire at all. Above threshold, stronger stimuli don't produce stronger action potentials. Thus, action potentials are not graded (proportional to stimulus strength) like local potentials are. Action potentials are nondecremental. They don't get weaker with distance. The last action potential at the end of a nerve fiber is just as strong as the first one in the trigger zone, no matter how far away-even in a pain fiber that extends from your toes to your brainstem. Action potentials are irreversible. If a neuron reaches threshold, the action potential goes to completion; it can't be stopped once it begins. In some respects, we can compare the firing of a neuron to the firing of a gun. As the trigger is squeezed, a gun either fires with maximum force or doesn't fire at all (analogous to the all-or-none law). You can't fire a fast bullet by squeezing the trigger hard or a slow bullet by squeezing it gently-once the trigger is pulled to its "threshold," the bullet always leaves the muzzle at the same velocity. And, like an action potential, the firing of a gun is irreversible once the threshold is reached; neither a bullet nor an action potential can be called back. 12.4e The Refractory Period During an action potential and for a few milliseconds after, it is difficult or impossible to stimulate that region of a neuron to fire again. This period of resistance to restimulation is called the refractory period. It is divided into two phases: an absolute refractory period in which no stimulus of any strength will trigger a new action potential, followed by a relative refractory period in which it is possible to trigger a new action potential, but only with an unusually strong stimulus. The absolute refractory period lasts from the start of the action potential until the membrane returns to the resting potential-that is, for as long as the Na* channels are open and subsequently inactivated. The relative refractory period lasts until hyperpolarization ends. During this period, K' channels are still open. A new stimulus tends to admit Na and depolarize the membrane, but K diffuses out through the open channels as Na* comes in, and thus opposes the effect of the stimulus. It requires an especially strong stimulus to override the K* outflow and depolarize the cell enough to set off a new action potential. By the end of hyperpolarization, K* channels are closed and the cell is as responsive as ever. The refractory period refers only to a small patch of membrane where an action potential has already begun, not to the entire neuron. Other parts of the neuron can still be stimulated while a small area of it is refractory, and even this area quickly recovers once the nerve signal has passed. 12.4f Signal Conduction in Nerve Fibers If a neuron is to communicate with another cell, a signal has to travel to the end of the axon. We now examine how this is achieved. Unmyelinated Fibers and Continuous Conduction Unmyelinated fibers present a relatively simple case of signal conduction, easy to understand based on what we have already covered ( (4 fig. 12.17). An unmyelinated fiber has voltage-gated channels along its entire length. When an action potential occurs at the trigger zone, Na* enters the axon and diffuses for a short distance just beneath the plasma membrane. The resulting depolarization excites voltage-gated channels immediately distal to the action potential. Sodium and potassium channels open and close just as they did at the trigger zone, and a new action potential is produced. By repetition, this excites the membrane immediately distal to that. This chain reaction continues until the traveling signal reaches the end of the axon. Because this produces an uninterrupted wave of electrical excitation all along the fiber, this mechanism is called continuous conduction.

Following Loewi's work, the idea of electrical communication between cells fell into disrepute. Now, however, we realize that some neurons, neuroglia, and cardiac and unitary smooth muscle do indeed have electrical synapses, where adjacent cells are joined by gap junctions and ions diffuse directly from one cell into the next. These junctions have the advantage of quick transmission because there is no delay for the release and binding of neurotransmitter. They are important in synchronizing the activity of local suites of neurons in certain regions of the brain. Their disadvantage, however, is that they cannot integrate information and make decisions. The ability to do that is a property of chemical synapses, in which neurons communicate by neurotransmitters. Chemical synapses are also the site of learning and memory, the target of many prescription drugs, and the site of action of drugs of addiction, among other things. 12.5b Structure of a Chemical Synapse The axon terminal contains synaptic vesicles, many of which are "docked" at release sites on the plasma membrane, ready to release neurotransmitter on demand. A reserve pool of synaptic vesicles is located a little farther away from the membrane, tethered to the cytoskeleton. 12.5c Neurotransmitters and Related Messengers More than 100 neurotransmitters have been identified since Loewi's time. Neurotransmitters can be defined as molecules that are synthesized by a neuron, released when a nerve signal reaches an axon terminal or varicosity of the nerve fiber, and have a specific effect on a receiving cell's physiology. Most of them are small organic molecules that are released by exocytosis and bind to specific receptors on the receiving cell, but there are exceptions..

Acetylcholine is in a class by itself. It is formed from acetic acid (acetate) and choline.
Amino acid neurotransmitters include glycine, glutamate, aspartate, and y-aminobutyric acid (GABA).
Monoamines (biogenic amines) are synthesized from amino acids by removal of the - -COOH group. They retain the -NH, (amino group), hence their name. Some monoamine neurotransmitters are epinephrine, norepinephrine, dopamine, serotonin (5-hydroxytryptamine, or 5-HT), and histamine. The first three of these are in a subclass called catecholamines (CAT-eh-COAL-uh-meens)
Purines serving as neurotransmitters include adenosine and ATP (adenosine triphosphate).
Gases , specifically nitric oxide (NO) and carbon monoxide (CO), are inorganic exceptions to the usual definition of neurotransmitters. They are synthesized as needed rather than stored in synaptic vesicles; they simply diffuse out of the axon terminal rather than being released by exocytosis; and they diffuse into the postsynaptic neuron rather than bind to a surface receptor.
Neuropeptides are chains of 2 to 40 amino acids. Some examples are cholecystokinin (CCK) and the endorphins. Neuropeptides are stored in secretory granules (dense-core vesicles) that are about 100 nm in diameter, twice as large as typical synaptic vesicles. Some neuropeptides also function as hormones or as neuromodulators (see L section 12.5f). Some are produced not only by neurons but also by the digestive tract; thus, they are known as gut-brain peptides. Some of these cause cravings for specific nutrients such as fat, protein, or carbohydrates (see El section 26.1b) and may be associated with certain eating disorders. TABLE 12. Neurotransmitters (Selected Examples) Name Acetylcholine (ACh): Neuromuscular junctions, most synapses of autonomic nervous system, retina, and many parts of the brain; excites skeletal muscle, inhibits cardiac muscle, and has excitatory or inhibitory effects on smooth muscle and glands depending on location Amino Acids Glutamate: Cerebral cortex and brainstem: accounts for about 75% of all excitatory synaptic transmission in the brain; involved in learning and memory Aspartate: Spinal cord; effects similar to those of glutamate Glycine: Inhibitory neurons of the brain, spinal cord, and retina; most common inhibitory neurotransmitter in the spinal cord GABA: Thalamus, hypothalamus, cerebellum, occipital lobes of cerebrum, and retina; the most common inhibitory neurotransmitter in the brain Monoamines Norepinephrine: Sympathetic nervous system, cerebral cortex, hypothalamus, brainstem, cerebellum, and spinal cord; involved in dreaming, waking, and mood; excites cardiac muscle; can excite or inhibit smooth muscle and glands depending on location Epinephrine: Hypothalamus, thalamus, spinal cord, and adrenal medulla; effects similar to those of norepinephrine Dopamine: Hypothalamus, limbic system, cerebral cortex, and retina; highly concentrated in substantia nigra of midbrain; involved in elevation of mood and control of skeletal muscles Serotonin: Hypothalamus, limbic system, cerebellum, retina, and spinal cord; also secreted by blood platelets and intestinal cells; involved in sleepiness, alertness, thermoregulation, and mood Histamine: Hypothalamus; also a potent vasodilator released by mast cells of connective tissue and basophils of the blood Neuropeptides Substance P: Basal nuclei, midbrain, hypothalamus, cerebral cortex, small intestine, and pain-receptor neurons; mediates pain transmission Enkephalins: Hypothalamus, limbic system, pituitary, pain pathways of spinal cord, and nerve endings of digestive tract; act as analgesics (pain relievers) by inhibiting substance P; inhibit intestinal motility; modulate immune responses ß-endorphin: Digestive tract, spinal cord, and many parts of the brain; also secreted as a hormone by the pituitary; suppresses pain; secretion rises sharply during labor and delivery and in response to other pain situations Cholecystokinin: Cerebral cortex and small intestine; suppresses appetite We will see, especially in L chapter 15, that a given neurotransmitter does not have the same effect everywhere in the body. There are multiple receptor types in the body for a particular neurotransmitter-over 14 receptor types for serotonin, for example-and it is the receptor that governs what effect a neurotransmitter has on its target cell. Most human and other mammalian neurons can secrete two or more neurotransmitters and can switch from one to another under different circumstances. 12.5d Synaptic Transmission Some neurotransmitters are excitatory, some are inhibitory, and for some the effect depends on what kind of receptor the postsynaptic cell has. Some open ligand-gated ion channels and others act through second messengers. Bearing this diversity in mind, we will examine three kinds of synapses with different modes of action. An Excitatory Cholinergic Synapse A cholinergic synapse employs acetylcholine (ACh) as its neurotransmitter. ACh excites some postsynaptic cells (such as skeletal muscle) and inhibits others (such as cardiac muscle), but this discussion will describe an excitatory action. The steps in transmission at such a synapse are as follows ([) fig. 12.23):
1. The arrival of a nerve signal at the axon terminal opens voltage-gated calcium channels.
2. Ca2+ enters the terminal and triggers exocytosis of the synaptic vesicles, releasing ACh.
3. Empty vesicles drop back into the cytoplasm to be refilled with ACh, while synaptic vesicles in the reserve pool move to the active sites and release their ACh-a bit like a line of Revolutionary War soldiers firing their muskets and falling back to reload as another line moves to the fore.
4. Meanwhile, ACh diffuses across the synaptic cleft and binds to ligand-gated channels on the postsynaptic neuron. These channels open, allowing Na* to enter the cell and K* to leave. Although illustrated separately, Na* and K* pass in opposite directions through the same gates.

As Na* enters, it spreads out along the inside of the plasma membrane and depolarizes it, producing a local voltage shift called the postsynaptic potential. Like other local potentials, if this is strong and persistent enough (that is, if enough current makes it to the axon hillock), it opens voltage-gated ion channels in the trigger zone and causes the postsynaptic neuron to fire. An Inhibitory GABA-ergic Synapse Synapses that employ y-aminobutyric acid (GABA) as their neurotransmitter are called GABA-ergic synapses. Amino acid neurotransmitters such as GABA work by the same mechanism as ACh; they bind to ion channels and cause immediate changes in membrane potential. The release of GABA and binding to its receptor are similar to the preceding case. The GABA receptor, however, is a chloride channel. When it opens, CI enters the cell and makes the inside even more negative than the resting membrane potential. The neuron is therefore inhibited, or less likely to fire. An Excitatory Adrenergic Synapse An adrenergic synapse employs the neurotransmitter norepinephrine (NE), also called noradrenaline. NE, other monoamines, and neuropeptides act through second-messenger systems such as cyclic AMP (cAMP). The receptor is not an ion channel but a transmembrane protein associated with a G protein on the inner face of the membrane.
The unstimulated NE receptor is bound to a G protein.
Binding of NE to the receptor causes the G protein to dissociate from it.
The G protein binds to adenylate cyclase and activates this enzyme, which converts ATP to cAMP.
Cyclic AMP can induce several alternative effects in the cell.
One effect is to produce an internal chemical that binds to a ligand-gated ion channel from the inside, opening the channel and depolarizing the cell.
Another is to activate preexisting cytoplasmic enzymes, which can lead to diverse metabolic changes (for example, inducing a liver cell to break down glycogen and release glucose into the blood).
Yet another is for cAMP to induce genetic transcription, so that the cell produces new enzymes leading to diverse metabolic effects Although slower to respond than cholinergic and GABA-ergic synapses, adrenergic synapses do have an advantage- signal amplification. A single NE molecule binding to a receptor can induce the formation of many cAMPs, each of those can activate many enzyme molecules or induce the transcription of a gene to generate numerous mRNA molecules, and each of those can result in the production of a vast number of enzyme molecules and metabolic products such as glucose molecules Stages of transcription As complex as synaptic events may seem, they typically require only 0.5 ms or so-an interval called synaptic delay. This is the time from the arrival of a signal at the axon terminal of a presynaptic cell to the beginning of an action potential in the postsynaptic cell. 12.5e Cessation of the Signal It is important not only to stimulate a postsynaptic cell but also to turn off the stimulus in due time. Otherwise the postsynaptic neuron could continue firing indefinitely, causing a breakdown in physiological coordination. But a neurotransmitter molecule binds to its receptor for only 1 ms or so, then dissociates from it. If the presynaptic cell continues to release neurotransmitter, one molecule is quickly replaced by another and the postsynaptic cell is restimulated. This immediately suggests a way of stopping synaptic transmission-stop adding new neurotransmitter and get rid of that which is already there. The first step is achieved simply by the cessation of signals in the presynaptic nerve fiber.
Neurotransmitter degradation. An enzyme in the synaptic cleft breaks the neurotransmitter down into fragments that have no stimulatory effect on the postsynaptic cell. Depicted here is acetylcholinesterase (AChE) breaking ACh down into choline and acetate.
Reuptake. A neurotransmitter or its breakdown products are reabsorbed by transport proteins in the axon terminal, removing them from the synapse and ending their stimulatory effect. Choline from ACh is recycled to make new ACh. Amino acid and monoamine neurotransmitters are similarly reabsorbed, then broken down within the axon terminal by an enzyme called monoamine oxidase (MAO). Some antidepressant drugs work by inhibiting MAO. Some cases of autism, attention-deficit/hyperactivity disorder (ADHD), parkinsonism, and depression stem from mutations that render some of these transport proteins nonfunctional.
Diffusion. Neurotransmitters or their breakdown products simply diffuse away from the synapse into the nearby extracellular fluid. As shown in, this is what happens to the acetate component of ACh, but in other cases, the neurotransmitter escapes the synapse intact. In the CNS, astrocytes absorb stray neurotransmitters and return them to the presynaptic neurons. In ganglia of the PNS, it seems that the satellite cells that surround neurons perform this role: this is an area of current scientific investigation. 12.5f Neuromodulators Neurons sometimes secrete chemical signals that have long-term effects on entire groups of neurons instead of brief, quick effects at an individual synapse. Some call these neuromodulators to distinguish them from neurotransmitters; others use the term neurotransmitter broadly to include these. Neuromodulators adjust, or modulate, the activity of neuron groups in various ways: increasing the release of neurotransmitters by presynaptic neurons; adjusting the sensitivity of postsynaptic neurons to neurotransmitters; or altering the rate of neurotransmitter reuptake or breakdown to prolong their effects. The simplest neuromodulator is the gas nitric oxide (NO). NO diffuses readily into a postsynaptic cell and activates second-messenger pathways with such effects as relaxing smooth muscle. This has the effect of dilating small arteries and increasing blood flow to a tissue; this is the basis for the action of drugs for erectile dysfunction. The neuropeptides are neuromodulators; among these are the enkephalins and endorphins , which inhibit spinal neurons from transmitting pain signals to the brain (see L section 16.2d). Other neuromodulators include hormones and some neurotransmitters such as dopamine, serotonin, and histamine. The last point may seem confusing, but the terms neurotransmitter, hormone, and neuromodulator define not so much the chemical itself, but the role it plays in a given context. One chemical can play two or more of these roles in different places and circumstances. 12.6 Neural Integration Synaptic delay slows the transmission of nerve signals; the more synapses there are in a neural pathway, the longer it takes information to get from its origin to its destination. You may wonder, therefore, why we have synapses-why a nervous pathway is not, indeed, a continuous "wire" as biologists believed before Cajal. The presence of synapses is not due to limitations on axon length-after all, one nerve fiber can reach from your toes to your brainstem. (In the neck of the giraffe, the recurrent laryngeal nerve has nerve fibers 4.6 m, or 15 ft, long. Nerve fibers from the hind foot to the brainstem are even longer by far.) We also have seen that cells communicate much more quickly through gap junctions than through chemical synapses. So why have chemical synapses at all? What we value most about our nervous system is its ability to process information, store it, and make decisions-and chemical synapses are the decision-making devices of the system. The more synapses a neuron has, the greater its information-processing capability. At this moment, you are using certain pyramidal cells of the cerebral cortex (see L fig. 12.5a) to read and comprehend this passage. Each pyramidal cell has about 40,000 synaptic contacts with other neurons. The cerebral cortex alone (the main information-processing tissue of your brain) is estimated to have 100 trillion (1014) synapses. To get some impression of this number, imagine trying to count them. Even if you could count two synapses per second, day and night without stopping, and you were immortal, it would take you 1.6 million years. The ability of your neurons to process information, store and recall it, and make decisions is called neural integration. 12.6a Postsynaptic Potentials Neural integration is based on the postsynaptic potentials produced by neurotransmitters. Remember that a typical neuron has a resting membrane potential (RMP) of about -70 mV and a threshold of about -55 mV. A neuron has to be depolarized to this threshold in order to produce action potentials. Any voltage change in that direction makes a neuron more likely to fire and is therefore called an excitatory postsynaptic potential (EPSP). EPSPs usually result from Na+

in the pool. Some input neurons form multiple synapses with a single postsynaptic cell. They can produce EPSPs at all points of contact with that cell and, through spatial summation, make it fire more easily than if they synapsed with it at only one point. Within the discharge zone of an input neuron, that neuron acting alone can make the postsynaptic cells fire. But in a broader facilitated zone , it synapses with still other neurons in the pool, with fewer synapses on each of them. It can stimulate those neurons to fire only with the assistance of other input neurons; that is, it facilitates the others. It "has a vote" on what the postsynaptic cells in the facilitated zone will do, but it cannot determine the outcome by itself. Such arrangements, repeated thousands of times throughout the central nervous system, give neural pools great flexibility in integrating input from several sources and "deciding" on an appropriate output. Types of Neural Circuits The functioning of a radio can be understood from a circuit diagram showing its components and their connections. Similarly, the functions of a neural pool are partly determined by its neural circuit-the pathways among its neurons. Just as a wide variety of electronic devices are constructed from a relatively limited number of circuit types, a wide variety of neural functions result from the operation of four principal kinds of neural circuits (L fig. 12.32):

In a diverging circuit , an individual neuron sends signals to multiple downstream neurons, or one neural pool may send output to multiple downstream neural pools. Each of those neurons or neural pools may communicate with several more, so input from just one pathway may produce output through hundreds of others. Such a circuit allows signals from one motor neuron of the brain, for example, to ultimately stimulate thousands of muscle fibers. Page 451
A converging circuit is the opposite of a diverging circuit-input from many nerve fibers or neural pools is funneled to fewer and fewer intermediate or output pathways. For example, you have a brainstem respiratory center that receives converging information from other parts of your brain, blood chemistry sensors in your arteries, and stretch receptors in your lungs. The respiratory center can then produce an output that takes all of these factors into account and sets an appropriate pattern of breathing.
In a reverberating circuit , neurons stimulate each other in a linear sequence from input to output neurons, but some of the neurons late in the path send axon collaterals back to neurons earlier in the path and restimulate them. As an exceedingly simplified model of such a circuit, consider a path such as A -B -C-, D, in which neuron C sends an axon collateral back to A. As a result, every time C fires it not only stimulates output neuron D, but also restimulates A and starts the process over. Such a circuit produces a prolonged or repetitive effect that lasts until one or more neurons in the circuit fail to fire, or an inhibitory signal from another source stops one of them from firing. A reverberating circuit sends repetitious signals to your diaphragm and intercostal muscles, for example, to make you inhale. Sustained output from the circuit ensures that the respiratory muscles contract for the 2 seconds or so that it normally takes to fill the lungs. When the circuit stops firing, you exhale; the next time it fires, you inhale again. Reverberating circuits may also be involved in short-term memory, as discussed in the next section, and they may play a role in the uncontrolled "storms" of neural activity that occur in epilepsy.
In a parallel after-discharge circuit , an input neuron diverges to stimulate several chains of neurons. Each chain has a different number of synapses, but eventually they all reconverge on one or a few output neurons. Since the chains differ in total synaptic delay, their signals arrive at the output neurons at different times, and the output neurons may go on firing for some time after input has ceased. Unlike a reverberating circuit, this type has no feedback loop. Once all the neurons in the circuit have fired, the output ceases. Continued firing after the stimulus stops is called after-discharge. It explains why you can stare at a lamp, then close your eyes and continue to see an image of it for a while. Such a circuit is also important in withdrawal reflexes, in which a brief pain produces a longer-lasting output to the limb muscles and causes you to draw back your hand or foot from danger. Serial and Parallel Processing In relation to these circuit types, the nervous system handles information in two modes called serial and parallel processing. In serial processing , neurons and neural pools relay information along a pathway in a relatively simple linear fashion and can process only one flow of information at a time. For example, you can read your e-mail or listen to a class lecture, and the language recognition centers of your brain can process one linguistic input or the other; however, you can't do both simultaneously. To understand the e-mail, you have to stop paying attention to the lecture; to understand the lecture, you have to stop checking your e-mail. You may jump back and forth between one and the other, only half understanding each, but you can't simultaneously process the written message in an e-mail and the spoken language of the lecture. Each must be processed separately and serially. In parallel processing , information is transmitted along diverging circuits through different pathways that act on it simultaneously, to different purposes. For example, when you're driving your car, your visual system (eye and brain) must simultaneously process information about color, shape, depth of field, and motion in the scene before your eyes. This requires complex parallel processing circuits from the retinas of your eyes through the visual centers at the rear of your brain. At the same time, you must process traffic sounds and signals from your body's own joint and motion sensors to know, for example, how hard you are pressing the gas or brake pedal. Efficient simultaneous processing of such information is crucial to your own ability to drive safely. Serial and parallel processing certainly occur as well in innumerable unconscious processes much simpler than the foregoing examples. 12.6e Memory and Synaptic Plasticity You may have wondered as you studied this chapter, How am I going to remember all of this? It seems fitting that we end this chapter with the subject of how memory works, for you now have the information necessary to understand its cellular and chemical basis. The things we learn and remember aren't stored in individual "memory cells" in the brain. You don't have a neuron assigned to remember your phone number and another to remember your grandmother's face, for example. Instead, the physical basis of memory is a pathway through the brain called a memory trace (engram 29), in which new synapses have formed or existing synapses have been modified to make transmission easier. In other words, synapses aren't fixed for life; in response to experience, they can be added, taken away, or modified to make transmission easier or harder. Indeed, synapses can be created or deleted in as little as 1 or 2 hours. The ability of synapses to change is called synaptic plasticity. Think about when you learned as a child to tie your shoes. The procedure was very slow, confusing, and laborious at first, but eventually it became so easy you could do it with little thought-like a motor program playing out in your brain without requiring your conscious attention. It became easier to do because the synapses in a certain pathway were modified to allow signals to travel more easily across them than across "untrained" synapses thus creating your motor memory for the task. The process of making transmission easier is called synaptic potentiation (one form of synaptic plasticity). Neuroscientists still argue about how to classify the various forms of memory, but three kinds often recognized are immediate memory, short- term memory, and long-term memory. We also know of different modes of synaptic potentiation that last from just a few seconds to a lifetime, and we can correlate these at least tentatively with different forms of memory. Immediate Memory Immediate memory is the ability to hold something in mind for just a few seconds. By remembering what just happened, we get a feeling for the flow of events and a sense of the present. Immediate memory is indispensable to the ability to read; you must remember the earliest words of a sentence until you get to its end in order to extract any meaning from it. You couldn't make any sense of what you read if you forgot each word as soon as you moved on to the next one. Immediate memory may be based on reverberating circuits. Our impression of what just happened can thus echo in our minds for a few seconds as we experience the present moment and anticipate the next one. Short-Term Memory

Short-term memory (STM) lasts from a few seconds to a few hours. Information stored in STM may be quickly forgotten if you stop mentally reciting it, you are distracted, or you have to remember something new. Working memory is a form of STM that allows you to hold an idea in mind long enough to carry out an action such as calling a telephone number you just looked up, working out the steps of a mathematics problem, or searching for a lost set of keys while remembering where you've already looked. It is limited to a few bits of information such as the digits of a telephone number. Evidence suggests that working memory resides in a circuit of facilitated synapses that remain quiescent (consuming little energy) most of the time, but are reactivated by new stimulation. Making it easier to transmit signals across a synapse is called synaptic facilitation (different from the facilitation of one neuron by another that we studied earlier in the chapter). Synaptic facilitation can be produced by tetanic stimulation, the rapid arrival of repetitive signals at a synapse. Each signal causes a certain amount of Ca2+ to enter the axon terminal. If signals arrive rapidly, the neuron cannot pump out all the Ca2* admitted by one action potential before the next action potential occurs. More and more Ca2+ accumulates in the terminal. Since Cat is what triggers the release of neurotransmitter, each new signal releases more neurotransmitter than the one before. With more neurotransmitter, the EPSPs in the postsynaptic cell become stronger and stronger, and that cell is more likely to fire. Memories lasting for a few hours, such as remembering what someone said to you earlier in the day or remembering an upcoming appointment, may involve posttetanic potentiation. In this process, the Ca2+ level in the axon terminal stays elevated for so long that another signal, coming well after the tetanic stimulation has ceased, releases an exceptionally large burst of neurotransmitter. That is, if a synapse has been heavily used in the recent past, a new stimulus can excite the postsynaptic cell more easily. Thus, your memory may need only a slight jog to recall something from several hours earlier. Long-Term Memory Long-term memory (LTM) lasts up to a lifetime and is less limited than STM in the amount of information it can store. LTM allows you to memorize the lines of a play, the words of a favorite song, or (one hopes!) textbook information for an exam. On a still longer timescale, it enables you to remember your name, the route to your home, and your childhood experiences. There are two forms of long-term memory: explicit and implicit. Explicit or declarative memory is the retention of events and facts that you can put into words-numbers, names, dates, and so forth. You must think to remember these things. Implicit memory is the memory of things that come reflexively or unconsciously, including emotional memories (such as the fear of being stung if a wasp lands on you) and procedural memory, the retention of motor skills-how to tie your shoes, play a musical instrument, or type on a keyboard. These forms of memory involve different regions of the brain but are probably similar at the cellular level. Some LTM involves the physical remodeling of synapses or the formation of new ones through the growth and branching of axon terminals and dendrites. In the pyramidal cells of the brain, the dendrites are studded with knoblike dendritic spines that increase the area of synaptic contact (see L fig. 12.5a). Studies on fish and other experimental animals have shown that social and sensory deprivation causes these spines to decline in number, while a richly stimulatory environment causes them to proliferate-an intriguing clue to the importance of a stimulating environment to infant and child development. In some cases of LTM, a new synapse grows beside the original one, giving the presynaptic cell twice as much input into the postsynaptic cell. LTM can also be grounded in molecular changes called long-term potentiation (LP ). This involves NMDA receptors, which are glutamate- binding receptors found on the dendritic spines of pyramidal cells. NMDA receptors are usually blocked by magnesium ions (Mg 2+), but when they bind glutamate and are simultaneously subjected to high-frequency stimulation, they expel the Mg?+ and open to admit Ca?+ into the dendrite. When Ca?+ enters, it acts as a second messenger with multiple effects. A high Ca?+ level activates enzymes called protein kinases, which phosphorylate (add phosphate to) proteins employed in building and strengthening synapses. The neuron also produces even more NMDA receptors, making it more sensitive to glutamate, and it may send signals such as nitric oxide (NO) back to the presynaptic cell to enhance its release of neurotransmitter. You can see that in all of these ways, long-term potentiation can increase transmission across "experienced" synapses. Remodeling a synapse or installing more neurotransmitter receptors has longer-lasting effects than facilitation or posttetanic potentiation. How We Forget Forgetting is arguably as important as remembering; we would likely be driven mad if we couldn't forget the myriad trivial things we encounter every day. People with a pathological inability to forget trivial information have great difficulty in reading comprehension and other functions that require us to distinguish what is important from what is not. Immediate and short-term memories vanish simply as neural circuits cease to fire. Long-term memories can be erased by a process of long- term depression (LTD). Low-frequency stimulation of a synapse results in low levels of intracellular Ca2t. This activates protein phosphatases, which dephosphorylate synaptic proteins such as actin microfilaments that support dendritic spines. These proteins are then degraded by proteasomes (see El section 3.4h, E fig. 3.31), which tear down dendritic spines and remove little-used synapses from the neural circuits. The anatomical sites of memory in the brain are discussed in Gl section 14.5d. Regardless of the sites, however, the cellular mechanisms are as described here.

Neurophysiology: Structure, Function, and Communication of Neurons, Summaries of Physiology

Related documents

Partial preview of the text

Download Neurophysiology: Structure, Function, and Communication of Neurons and more Summaries Physiology in PDF only on Docsity!

12.1 OVERVIEW OF THE NERVOUS SYSTEM