Nerve Cells Bhatnagar, S. C. (2008); Chapter 5. Introduction Two main types of cell in the nervous...

Nerve Cells

Bhatnagar, S. C. (2008); Chapter 5

Introduction

Two main types of cell in the nervous system: nerve cells and neuroglial cells.

Nerve cells or neurons are the basic functional unit in the CNS. More than 15 billion nerve

cells. Neuroglial cells or glial cells

support, protect and help in the repair of nerve cells. App 40-50 times as many glial

cells to neuron cells

Neuron

Their main role is to process and transmit information.

Through excitatory and inhibitory impulses, nerve cells serve all sensorimotor activities and higher mental functions, including attention, memory, thinking, language, etc.

Neurons are typically 4 to 100 micrometers in diameter.

Neurons

Each neuron consists of: Cell body or soma Two types of processes: Dendrites & Axons

The cell body and dendritic tree receive inputs from other neurons, and the axon transmits output signals to other nerve cells, muscles and glands.

Nerve Cell Structure Cell body: Two major components –

Nucleus and cytoplasm. Cytoplasm – contains microscopic

organelles such as mitochondria, ribosomes, lysosomes, and golgi complexes. Primary function is to metabolize

protein for the maintenance, growth and viability of the cell

Cell bodies not only utilize and convert outside glucose to generate energy, but also manufacture their own protein. This protein is conducted through

microtubules through the axons.

Nerve Cell Structure Mitochondria - "cellular power plants“

Converts organic materials into energy in the form of ATP .

Lysosomes – Participates in intracellular digestion.

Ribosomes – Help in assembling protein. Is like a factory that builds a protein from a set of

genetic instructions Golgi bodies/complexes – Responsible for

protein secretion and functions as a central delivery system for the cell.

Nerve Cell Structure

•The cell membrane refers to the structure that separates the inside of the cell from the outside environment.

•Embedded in the membrane are protein channels that permit certain ions (ie., semi permeable) to cross through the membrane at a controlled rate.


Nucleus: Controlling center of the cell and contains the genetic material, DNA (Deoxyribonucleic acid). DNA is a nucleic acid that contains the

genetic instructions used in the development and functioning of all known living organisms.

Often compared to a set of blueprints.

Nucleolus within the nucleus is the site of assembly of ribosomes and contain RNA which plays a role in protein synthesis.

Double Helix structure of a DNA sequence

Nerve Cell Structure Dendrites are primarily afferent

and carries information to the cell body from the synaptic sites.

Dendrites tend to be short and have many branches. The branching of dendrites is

known as arborization. Increases the ‘reach’ of each

individual neuron


Axons originate from a cone-shaped regions of the cell – Axon hillock Is the part of the neuron that has the greatest density of

voltage-dependent sodium channels. And is the most easily-excited part of the neuron, and

serves as the spike initiation zone for the axon.


Axons are longer and are efferent projections. Axon + covering sheath = nerve fiber

Axons terminate by branching into a number of smaller filaments – Telodendria Telodendria have synaptic knobs that contain

various neurotransmitters at their end.


The diameter and presence/absence of myelin sheath determines the speed of nerve conduction.

Myelin is an electrically insulating phospholipid (fatty) layer that surrounds the axons of many neurons. Myelin sheath is formed in small segments that

are interrupted by intervals – Nodes of Ranvier During neural conduction, electricity jumps from

one node to the next – Saltatory conduction This accelerates nerve conduction up to 120 m/sec.

Neuron


Myelin sheath is an outgrowth of glial cells: Schwann cells supply the myelin for the PNS

neurons while oligodendrocytes supply it to those of the CNS.

Myelin growth begins during fetal period and continues till puberty – Myelogenesis The growth rate and time span of myelogenesis is

related to the development of sensori-motor and cognitive skills.

Damage to myelin sheath or its production in the CNS will impair nerve conduction such as in multiple sclerosis.


Synapse – connection point between neurons Adult nervous system have about 100 to 500 trillion

synapses. Synapses have three parts – knob, cleft, and receptive site. Knobs contain vesicles of neurotransmitters that are

released during activation. The released neurotransmitters commute across the

synapse and stimulate the receptive site which can be a dendrite (axodendritic synapse), axons (axoaxonic synapse) or cell body (axosomatic synapse)

Receptive sites at adjacent postsynaptic neurons are chemically activated and generate electrical impulses that are carried to its body.

Nerve Bundles

Synapse

Classification of neuron types

Differ by shape, size, structure, and function. Based on the number of processes:

Unipolar - Dendrite and axon emerging from same process. Are ‘T’ shaped. Ex., Spinal dorsal root ganglions

Bipolar - single axon and single dendrite on opposite ends of the soma. Ex., neurons in the retina, olfactory and auditory system.

Multipolar - more than two dendrites. Mostly found in the CNS. Ex., Purkinje cells,

pyramidal cells.

Neuron classification

Classification of neuron types

Based on axon length: Golgi I - neurons with long-projecting (inches to

feet) axonal processes. Ex., sensory and motor tracts

Golgi II - neurons whose axonal process projects locally. Ex., Interneurons that connect with other adjacent neurons

Classification of Neurons Based on function:

Afferent neurons convey information from tissues and organs into the central nervous system.

Efferent neurons transmit signals from the central nervous system to the effector cells.

Interneurons connect neurons within specific regions of the central nervous system.

Based on action on other neurons: Excitatory neurons evoke excitation of their target

neurons. Inhibitory neurons evoke inhibition of their target neurons.

Inhibitory neurons are often interneurons. Modulatory neurons evoke more complex effects on other

neurons.

Neuronal circuits

Convergent circuit – Postsynaptic neurons receives information from a number of neurons of either same source or different sources.

Divergent circuit – Amplifies an impulse.

Lateral inhibition –Results in sharpening the response by inhibiting adjacent neurons.

Reverberating circuits – A self-propagating system that continues activation unless blocked by an external system.

Convergent circuit

Lateral Inhibition

Divergent circuit

Reverberating circuit

_+

Physiology - Nerve Conduction

Terminology Synapse

Specialized points for communication between a neuron and another neuron, a muscle cell, or a gland

Presynaptic terminal Formed by the axon end-projections of the neuron transmitting a

signal Postsynaptic terminal

Formed by the membrane region of the receiving cell Synaptic cleft

The space between the two terminals Neurotransmitters

Contained within vesicles in the presynaptic terminal Used to transmit information across the synaptic cleft

Nerve Physiology

A neuron that is not transmitting a signal is said to be at its Resting State. At this state, there is a

difference between electrical charges on the outer and inner sides of the membrane.

Fig. 2-13, p. 40

Nerve Physiology

Resting membrane potential = ~ -70 mV The inside of the neuron is negatively

charged relative to the outside because of the large, negatively charged molecules in the cytoplasm.

Inside the cell – low in sodium (Na+) and high concentration of potassium (K+) cells.

However, there is some spontaneous passive exchange of ions across the membranes. Sodium ions enter the membrane. (making

it more positive)

Resting potential & the Sodium-potassium pump The sodium-potassium

active pump maintains concentration gradients for both sodium and potassium ions. ATP (Adenosine

triphosphate) is the source of energy for this pump.

A large protein in the plasma membrane provides the doorway through which sodium and potassium ions can move.

Animation

Sodium-potassium pump

The addition of a phosphate group from ATP changes the shape of the protein and the sodium is expelled.

The phosphate is released and, as the protein returns to its former shape, two potassium ions are moved across the membrane.

Animation

Sodium-potassium pump

Nerve Excitability Hyperpolarization – Cell interior becomes

more negative. Technically means ‘more polarized’

Depolarization – Cell interior becomes ‘less’ negative (i.e., changing towards positive charge)

Nerve excitability refers to the nerve cells response to external stimuli (i.e., chemical or temperature change, electrical pulse, or nerve tapping) and the conversion of this response into a nerve impulse or Action Potential.

Nerve Excitability

Action potential - Temporary reversal of the charges on the neuron cell surface membrane. Results in the interior of cell becoming more positive –

That is, the cell gets depolarized. In most neural cells, to trigger an action

potential, a change of at least 10 mV (i.e., change from -70 mV to -60 mV) is required. Neuron Threshold value. Not all stimuli are strong enough to reach this

threshold value. Also threshold potential value varies with type of

cells.

Nerve Excitability

Initially, the local membrane depolarization caused by an excitatory stimulus causes some voltage-gated sodium channels in the neuron cell surface membrane to open.

This causes sodium ions to diffuse in through the channels. And since they are positively charged, this begins

a reversal in the potential difference across the membrane from negative-inside to positive-inside.

Action Potential

Once a membrane potential of around +40 mV is reached, the voltage-sensitive gates of the sodium channels closes. The further influx of sodium is

prevented. While this occurs, the

voltage-sensitive activation gates on the potassium channels begin to open. This results in a large outward

movement of potassium ions.

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Action Potential

This movement of positive charge causes a reversal of the membrane potential to negative-inside (i.e., back towards the large negative-inside resting potential) - Repolorization

However the large outward current of potassium ions through the voltage-gated potassium channels causes a temporary overshoot of the electrical gradient, with the inside of the neuron being even more negative relative to the outside (~ -80 to -90 mV) than the usual resting potential. I.e., Results in the hyperpolarization of the cell.

Action Potential

This state is known as the absolute refractory period.

In the refractory state, the cell cannot fire another action potential until the membrane potential returns to its resting potential.

Animation Animation 2 The action potentials of most

nerves last 5-10 milliseconds.

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Action Potential or Nerve Conduction

In order for information to be transferred in the nervous system, the action potential, once generated, must travel down the axon.

The propagation of the action potential occurs because the influx of positive charge, during the rising phase, depolarizes the next segment of the membrane. Rapidly it works its way down the axon to the

presynaptical terminal, and initiates synaptic communication with another neuron or cell.


Animation


An action potential travels only in one direction. It cannot turn back on itself because the

membrane behind it is still refractory. Also Action potentials propagate without

decrement – Hence are called an "All or none" signal.


Aspects of the all-or-none law: If the stimulus is too low (i.e., below threshold),

there is no action potential - This is the "none" part.

If the stimulus is above a threshold the action potential is always the same size- it does not get larger for stronger stimuli - This is the “all” part

As the action potential travels along the axon it does not die out, but stays the same size.

Factors Influencing Action Potential Conduction Speed

Two factors – Axon diameter: Action potentials propagate

faster in axons of larger diameter because resistance to conduction is lower with larger diameters.

Myelination: Because all neurons cannot be gigantic to improve conduction speed, there is another mechanism to improve axonal conduction.

Factors Influencing Action Potential Conduction Speed

In myleinated axons, voltage-gated sodium channels are concentrated in the nodes of Ranvier.

Conduction velocity for ordinary nerve = ~1 meter/sec (depends upon diameter)

Conduction velocity for myelinated nerve = ~100 meters/sec

Conduction along these myelinated fibers is referred to as saltatory conduction.

Action Potential Conduction - Animation

Another animation!

Synapse

Neural synapses (also called chemical synapses) allow the neurons to form interconnected neural circuits.

The pre-synaptic neuron secretes the neurotransmitter at it bouton, which binds to post-synaptic receptors.

Physiological activities at the synapse

The release of neurotransmitter is triggered by the arrival of a nerve impulse or action potential and occurs through a rapid process known as exocytosis.

Within the pre-synaptic nerve terminal, vesicles containing neurotransmitters sit "docked" and ready at the synaptic membrane.


The arriving action potential produces an influx of calcium ions through voltage-dependent, calcium-selective ion channels.

Calcium ions then trigger a biochemical reaction which results in vesicles fusing with the presynaptic-membrane and releasing their contents to the synaptic cleft.


Receptors on the opposite side of the synaptic gap bind to these neurotransmitter molecules and respond by the opening of nearby ion channels in the post-synaptic cell membrane.

This causes ions to rush in or out and changes the membrane potential of the postsynaptic cell. The resulting change in voltage is

called a postsynaptic potential.

Review

Resting potential and Action potential- Animation

Synapse – Animation 1 Animation 2

Neurons - How they work video

Post-Synapse Postsynaptic potentials are changes in the

membrane potential of the postsynaptic neuron. Postsynaptic potentials are graded potentials

(unlike the “all or none” type of the action potentials). The amount of neurotransmitter released from the

presynaptic terminal is directly related to the total number of action potentials per unit time reaching the terminal.

An increase in either the strength of a stimulus or the duration of a stimulus to the presynaptic cell also results in the release of greater quantities of neurotransmitter.

Post-Synapse

The neurotransmitters bind to receptors on the postsynaptic neuron by having a particular shape or structure (kind of like the way a key fits into certain locks).

Typically these receptors react to the binding of neurotransmitters by opening or closing an ion channel thereby allowing ions to enter or leave the cell. It is these ions that alter the membrane potential of

the postsynaptic membrane/neuron.

Synapse 2Synapse

Postsynaptic PotentialsRemember, the neighboring neurons also

have a resting potential of about -70mV. There are two kinds of postsynaptic potentials.

If the opening of the ion channel (ex., sodium channels open & Na ions enter the cell) results in a net gain of positive charge across the membrane (i.e., the membrane gets depolarized), thereby bringing this neuron's potential closer to its firing threshold (which is about -55mV) – Excitatory postsynaptic potential (EPSP).

Postsynaptic Potentials

If, on the other hand, the opening of the ion channel (ex., potassium channels open & Ka ions leave the cell) results in a net gain of negative charge (i.e., the membrane gets hyperpolarized), thereby changing the charge across the membrane to be further from the firing threshold – Inhibitory postsynaptic potential (IPSP).

Excitatory Postsynaptic Potentials

Neurotransmitter binding leads to opening of ion channels and a local, instantaneous flow of sodium (Na+) or carbon (Ca+) into the neuron

Postsynaptic membrane becomes depolarized (less negative)

Influx of ions creates an EPSP and summation of EPSPs can lead to the generation of an action potential

Activation of synapses between a neuron and a muscle cell at the neuromuscular junction results in EPSPs that lead to excitation of the muscle

Inhibitory Postsynaptic Potential

Neurotransmitter binding leads to opening of CL- (chlorine) and/or K+ channels

Postsynaptic membrane becomes hyperpolarized (more negative)

Hyperpolarization can inhibit generation of an action potential

If EPSPs coincide with IPSPs, summation determines whether an action potential will be generated

Release of neurotransmitters from an axon terminal can be either facilitated or inhibited by the chemical action at an axoaxonic synapse

Postsynaptic Potentials EPSPs and IPSPs are transient

changes in the membrane potential.

EPSPs from a single synapse are generally far too small to trigger a response in the postsynaptic neuron. However, a neuron typically

receives synaptic inputs from about 10,000 other neurons, so the combined activity can cause large fluctuations in membrane potential.

If the postsynaptic cell is sufficiently depolarized, an action potential will occur in this postsynaptic neuron.

Postsynaptic Potentials With multiple inputs, postsynaptic potentials are

subject to summation, either spatially or temporally. Spatial summation:

If a cell is receiving input at two synapses that are near each other, their postsynaptic potentials add together. If the cell is receiving two EPSPs, they combine so

that the membrane potential is depolarized by the sum of the two changes.

If there are two IPSP, they also sum, and the membrane is hyperpolarized by that amount.

If the cell is receiving both inhibitory and excitatory postsynaptic potentials, they can cancel out, or one can be stronger than the other, and the membrane potential will change by the difference between them.

Postsynaptic Potentials

Temporal summation: When a cell receives inputs that

are close together in time, they are also added together, even if from the same synapse.

Thus, if a neuron receives an EPSP, and then the presynaptic neuron fires again or another presynaptic neuron creates another EPSP, then the membrane of the postsynaptic cell is depolarized by the total of the EPSPs.

Neural Networks

Neurotransmitters

Neurotransmitters are chemicals that are used to relay, amplify and modulate electrical signals between a neuron and another cell.

Traditionally two types – Small and large molecules. Small molecules – Produce short-lasting effects.

Include neurotransmitters such as acetylcholine, dopamine, norepinepherine, serotonin, glutamate, and γ – aminobutyric acid (GABA).

Dopamine, norepinepherine, serotonin, GABA – also called monoamines. Mainly produced in the brainstem

Large molecules – Long lasting effects. Includes Peptides such as enkephalin and endorphins.

Neurotransmitters

Acetylcholine (ACh) – Was the first neurotransmitter to be identified. It is the primary transmitter of the PNS but is also

present in the CNS. In the CNS, ACh regulates forebrain activity and

sleep/wakefulness cycles In the PNS, ACh controls voluntary movements of motor

fibers of the spinal and cranial nerves. Abnormal levels of ACh results in conditions such

as myasthenia gravis. Also implicated in Alzheimer's disease.

Neurotransmitters

Dopamine (DA) – Functions involved include:

Movement – Affects the basal ganglia motor loop. Shortage of dopamine (particularly in the substantia nigra

regions) causes Parkinson's disease (which is characterized by the loss of the ability to execute smooth, controlled movements).

Cognition and memory – Controls the flow of information from the frontal lobe to other areas of the brain. Disorders cause a decline in neurocognitive functions

( especially memory, attention and problem-solving) and is implied in disorders such as attention deficit disorder and negative schizophrenia.

Neurotransmitters

Dopamine functions Motivation and pleasure – Is associated with the

‘reward system’ Is released (particularly in areas such as the nucleus

accumbens) during naturally rewarding experiences such as food, sex, use of certain drugs and neutral stimuli that become associated with them.

Is associated with disorders such as depression and addictions.

Neurotransmitters

Norepinephrine – Is released when a host of physiological changes activated

by a stressful event (hence also known as a stress hormone).

It affects parts of the human brain where attention and impulsivity are controlled.

Along with epinephrine, this compound affects the “fight-or-flight” response by activating the sympathetic nervous system.

Also (along with dopamine) plays large role in attention and focus. People with ADD/ADHD, psychostimulant medications such

as Ritalin/Concerta and Dexedrine are prescribed to help increase levels of norepinephrine and dopamine.

Neurotransmitters

Serotonin – Although important for the CNS, 95% is found

peripherally in blood platelets and the gastrointestinal system.

In the CNS, serotonin is believed to play an important role in the regulation of mood, sleep, emesis (vomiting), sexuality and appetite.

Serotonin has been thought to play a part in many disorders, including depression, migraine, bipolar disorder and anxiety.

Neurotransmitters

GABA – Is a major inhibitory neurotransmitter found in the

CNS It regulates CNS activity by inhibiting the number of

neurons firing. Also known as the “brains natural calming agent.” Is used to treat epilepsy and hypertension. Loss of GABA producing neurons (and the resulting

higher proportion of dopamine) produces clinical conditions such as Huntington's chorea (a degenerative disorder characterized by involuntary movements).

Nerve Cells Bhatnagar, S. C. (2008); Chapter 5. Introduction Two main types of cell in the nervous...

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