THE NERVOUS SYSTEM: NEURAL

TISSUE

Nervous system functions

• 1. sensory function– sensory receptors detect internal and external stimuli– information is sent to CNS via sensory (afferent) neurons within sensory

nerves• 2. integrative function

– integrates = processing of information within the CNS– stores info and also makes decisions once info is processed– one important integrative function = perception– processed by interneurons within the CNS– 90% of the neurons within the CNS are interneurons

• 3. motor function– decision usually manifests itself as a motor command – contraction of a

muscle, secretion by a gland– motor commands travel along motor (efferent) neurons within motor nerves– commands are sent to effectors = muscles and glands

Nervous system includes all neural tissue in body

• about 3% of the total body weight• Central Nervous System

– Brain and spinal cord (brain = 100 billion neurons, SC = 100 million neurons)

• Peripheral Nervous System– All neural tissue outside CNS– includes the spinal and cranial nerves

A schematic of the vertebrate nervous system

Figure 21-6

• Neurons

Cells in Nervous Tissue

• Neuroglia

• about half the volume of cells in the CNS• smaller than neurons• 5 to 50 times more numerous• do NOT generate electrical impulses• divide by mitosis• Two types in the PNS

– Schwann cells– Satellite cells

• Four types in the CNS– Astrocytes– Oligodendrocytes– Microglia– Ependymal cells

Neuroglia (Glia)

• Largest of glial cells• Most numerous• Star shaped with many processes projecting from the cell body

-processes make contact with the capillaries supplyingCNS tissue, CNS neurons and the pia mater membranecovering the brain and spinal cord

• Help form and maintain blood-brain barrier– processes wrap around the blood capillaries and isolate the

neurons from their blood supply• Provide structural support for neurons• Maintain the appropriate chemical environment for generation of nerve

impulses/action potentials– regulate ion concentrations - generation of action potentials by neurons

• Take up excess neurotransmitters from the synapse • Regulate nutrient concentrations for neuron survival• Assist in neuronal migration during brain development• Perform repairs to stabilize tissue – scar formation???

Astrocytes

Oligodendrocytes

• Most common glial cell type

• Each forms myelin sheath around the axons of neurons in CNS

• Analogous to Schwann cells of PNS

• Form a supportive network around CNS neurons

• fewer processes than astrocytes• round or oval cell body

Microglia

• Small cells found near blood vessels• Phagocytic role - clear away dead cells• protect CNS from disease through phagocytosis of microbes• migrate to areas of injury where they clear away debris of

injured cells - may also kill healthy cells

• few processes• derived from mesodermal cells that also give rise to monocytesand macrophages

Ependymal Cells

• Form epithelial membrane lining cerebral cavities (ventricles) & central canal - that contain CSF

• Produce & circulate the cerebrospinal fluid (CSF) found in these chambers

• CSF = colorless liquid that protects the brain and SC against chemical & physical injuries, carries oxygen, glucose and other necessary chemicals from the blood to neurons and neuroglia

• epithelial cells arranged in asingle layer• range in shape from cuboidalto columnar

PNS: Satellite Cells

• Flat cells surrounding PNS axons

• Support neurons in the PNS & help regulate the chemical environment surrounding the neurons

• Found in the ganglia of the PNS

PNS: Schwann Cells

• each cell surrounds multiple unmyelinated PNS axons with a single layer of its plasma membrane

• produces part of the myelin sheath surrounding an axon in the PNS

• also contributes to regeneration of PNS axons

Neurons

•have the property of electrical excitability - ability to produceaction potentials or impulses in response to stimuli

•what is the main defining characteristic of neurons?

Representative Neuron

1. cell body or soma (or perikaryon) -single nucleus with prominent nucleolus (high synthetic activity)-Nissl bodies

-rough ER & free ribosomes for protein synthesis

-neurofilaments give cell shape and support –also move material inside cell-lipofuscin pigment clumps (harmless aging) - yellowish brown

http://www.horton.ednet.ns.ca/staff/selig/Activities/nervous/na1.htm

-the processes that emerge from the body of the neuron = nerve fibers-two kinds: dendrites & axons

2. Cell processes = dendrites (little trees)- the receiving or input portion of the neuron-short, tapering and highly branched-surfaces specialized for contact with other neurons – either with their axons of cell bodies

Neurons

3. Cell processes = axons• conduct impulses away from cell body

toward synaptic end bulbs

• sites for neurotransmitter storage

• joins the soma at a cone-shaped elevation = axon hillock

• first part of the axon = initial segment

• most impulses arise at the junction of the axon hillock and initial segment = trigger zone

• cytoplasm = axoplasm

• plasma membrane = axolemma

• side branches = collaterals arise from the axon

• axon and collaterals end in fine processes called axon terminals

• swollen tips called synaptic end bulbs contain vesicles filled with neurotransmitters

Axonal Transport• Cell body is the location for most protein synthesis

– neurotransmitters & repair proteins

• however the axon or axon terminals require neurotransmitters for signaling

• Axonal transport system moves substances to the synaptic terminals

– slow axonal flow• movement of axoplasm in one direction only -- away from cell body to the

terminals

• only 1-5 mm per day

• replenishes axoplasm in regenerating or maturing neurons

– fast axonal flow• moves organelles & neurotransmitters via microtubules

• at 200-400 mm per day

• transports material in either direction

• for transport to the terminals or for recycling things back to the cell body

Structural Classification of Neurons

• can classify neurons two main ways:– 1. Structural

– 2. Functional

• 1. based on number of processes found on cell body

– multipolar = several dendrites & one axon• most common cell type in the brain and SC

– bipolar neurons = one main dendrite & one axon• found in retina, inner ear & olfactory

– unipolar neurons = one process only, sensory only (touch, stretch)

• 2. or can classify by the name of the histologist that first described them • 3. or can classify them by their appearance

– e.g. pyramidal neurons

Structural Classification of Neurons

•Purkinje = cerebellum•Renshaw = spinal cord

Functional Classification of Neurons

• Sensory (afferent) neurons– transport sensory information from skin, muscles,

joints, sense organs & viscera to CNS

• Motor (efferent) neurons– send motor nerve impulses to muscles & glands

• Interneurons (association/integrative) neurons– connect sensory to motor neurons

– 90% of neurons in the body

The Nerve Impulse

Terms to know• membrane potential = electrical voltage difference

measured across the membrane of a cell• resting membrane potential = membrane potential of

a neuron measured when it is unstimulated– results from the build-up of negative ions in the cytosol

along the inside of the neuron’s PM– the outside of the PM becomes more positive– this difference in charge can be measured as potential

energy – measured in millivolts• polarization – change in membrane potential away

from resting MP– depolarization– repolarization– hyperpolarization

Ion Channels

• ion channels in the PM of neurons and muscles contributes to their excitability

• when open - ions move down their concentration gradients

• two types: gated and non-gated

1. Leakage (non-gated) or Resting channels: are always open, contribute to the resting potential-nerve cells have more K+ than Na+ leakage channels -as a result, membrane permeability to K+ is higher-so K+ leakage is the main factor in setting the resting membrane potential

2. Gated channels: channels can possess gates to open and close them-open and close in response to a stimulusA. voltage-gated: open in response to change in voltage - participate in the AP

B. ligand-gated: open & close in response to particular chemical stimuli (hormone, neurotransmitter, ion)C. mechanically-gated: open with mechanical stimulation

• Resting membrane potential is -70mV

• AP is triggered when the membrane potential reaches and exceeds a threshold (usually -55 MV)

Action Potential

• action potential = nerve impulse• takes place in two stages: depolarizing phase (more positive – e.g. -70 mV to -60mV)

and repolarizing phase (more negative - back toward resting potential – e.g. + 30 mV to +20 mV)

• followed by a hyperpolarizing phase or refractory period in which no new AP can be generated

The action potential

http://www.blackwellpublishing.com/matthews/channel.html

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• 1. neuron is at resting membrane potential (resting MP)• 2. neuron receives a signal

• Neurotransmitter (NT)

• 3. NT binds ligand-gated sodium channel (LGNa)• 4. LGNa channel opens• 5. Na flows into neuron = depolarization

• Inside of neuron (i.e. MP) becomes more positive

• 6. if neuron depolarizes enough to Threshold = Action Potential (AP)• 7. 1st stage of AP – opening of voltage-gated Na channelsc(VGNa)• 8. even more Na flows in through VGNa channels = BIG depolarization

• Membrane potential goes from negative to positive

• 9. closing of VGNa channels & opening of voltage-gated K channels• 10. BIG outflow of potassium through VGK channels = repolarization

• Inside of neuron (MP) becomes more negative

• 11. neuron repolarizes so much – it goes past resting and hyperpolarizes• 12. closing of VGK channels• 13. all voltage-gated channels closed, Na/K pump “resets” ion distribution to

resting situation

at a certain stage of depolarization, theMP alsoopens voltage-gated K+ channels which permitthe outflow of K+ . The Na+ channels close andthe MP becomes more negative returning toward resting MP

depolarization (increase in MP) results from opening of Na+ channels. This opens an increasing number of voltage-gated Na channels which depolarizes the membrane more. Once threshold is reached, a large # of voltage-gated Na+ channels open and a rapid increase in MP results

outflow of K+ restores the resting MP. Na+ channels begin to open again and K+ channels close. This results in hyperpolarization (below resting) results in a refractory period.

Continuous versus Saltatory Conduction

• Continuous conduction (unmyelinated fibers)– An action potential spreads

(propagates) over the surface of the axolemma

http://highered.mcgraw-hill.com/sites/0072437316/student_view0/chapter45/animations.html#

Saltatory Conduction

• Saltatory conduction-depolarization only at nodes of Ranvier - areas along the axon that are unmyelinated and where there is a high density of voltage-gated ion channels

-current carried by ions flows through extracellular fluid from node to node

http://www.blackwellpublishing.com/matthews/actionp.html

Rate of Impulse Conduction• not related to stimulus strength• Properties of axon• Presence or absence of myelin sheath

– myelin = 5 to 7X faster• Diameter of axon

– larger = faster conduction

Action Potentials in Nerve and Muscle• another excitable cell type = muscle

• muscle cells can generate their own action potential in response to the neuron’s

• are some notable differences vs. Neurons

• 1. entire muscle cell membrane versus only the axon of the neuron is involved

• 2. resting membrane potential differ– nerve is -70mV

– skeletal & cardiac muscle is closer to -90mV

• 3. AP duration is longer in muscles– nerve impulse is 1/2 to 2 msec

– muscle action potential lasts 1-5 msec for skeletal & 10-300msec for cardiac & smooth

• BUT fastest nerve conduction velocity is 18 times faster than velocity over skeletal muscle fiber

Synaptic Communication

• Synapse– Site of intercellular communication

between 2 neurons or between a neuron and an effector (e.g. muscle)

• Permits communication between neurons and other cells– Initiating neuron = presynaptic

neuron– Receiving neuron = postsynaptic

neuron• Most are axodendritic axon -> dendrite• Some are axoaxonic – axon > axon

Synapse

http://www.lifesci.ucsb.edu/~mcdougal/neurobehavior/modules_homework/lect3.dcr

• axon terminal swell to form synaptic end bulbs• site of neurotransmitter release

– multiple types of NTs can be found in one neuron type

• NTs will cause either and excitatory or inhibitory response in the post-synaptic neuron

• If the NT depolarizes the postsynaptic neuron = excitatory– change in membrane potential is called an excitatory postsynaptic potential

(EPSP)– produced through the opening of sodium channels or other cation channels

(inward)

• Some NTs will cause hyperpolarization = inhibitory– called an inhibitory postsynaptic potential (IPSP)– opening of chloride channels (inward) or potassium channels (outward)

• Neural activity depends on summation of all synaptic activity– Excitatory and inhibitory

Synapses

Synapses

http://www.blackwellpublishing.com/matthews/nmj.html

• Chemical – Membranes of pre and postsynaptic neurons do not

touch– Synaptic cleft exists between the 2 neurons – 20 to 50

nm– the electrical impulse cannot travel across the cleft –

indirect method is required – chemical messengers (neurotransmitters)

– Most common type of synapse– The neurotransmitter induces a postsynaptic potential in

the PS neuron • either an EPSP or an IPSP

– Communication in one direction only

Chemical synapse

– is the conversion of an electrical signal (presynaptic) into a chemical signal back into an electrical signal (postsynaptic)

• 1. nerve impulse arrives at presynaptic end bulbs• 2. fusion of synaptic vesicles to PM - role for calcium in this fusion• 3. release of NTs • 4. opening of channels in PM of postsynaptic neuron (e.g. sodium)• 5. postsynaptic potential develops – possible depolarization & triggering of AP in

postsynaptic neuron

Release of NTs from Synaptic end bulbs

Synaptic vesicles can befilled, exocytosed, andrecycled within a minute

• upon arrival of the AP into the synaptic end bulbs the opening of voltage-gated Ca2+ channels

• the influx of calcium promotes the “docking” of the synaptic vesicle with the PM and the exocytosis of their contents

• the synaptic vesicle components are then recycled for future use

• Electrical

– Direct physical contact between cells required

– Conducted through gap junctions

– Two advantages over chemical synapses• 1. faster communication – almost instantaneous

• 2. synchronization between neurons or muscle fibers– e.g. retina, heart-beat

Synapses

Neurotransmitters

• More than 100 identified• produced by neurons and stored

within the neuron• secrete these NTs in response to

generation of an electrical signal (action potential) by the neuron

• bind onto post-synaptic neurons (synapse) or target muscle cells (neuromuscular junction)

• some bind receptors on the target and cause channels to open in the target (e.g. ligand-gated sodium channels)

• others bind receptors on the post-synaptic neuron and result in the opening of LG channels through other mechanisms

• result in either excitation or inhibition of the post-synaptic neuron

Neuromuscular junction

Neurotransmitters• an important thing to consider is the removal of the

neurotransmitter from the synaptic cleft• Removal of NTs

– 1. Diffusion• move down concentration gradient out of the synaptic cleft

– 2. Enzymatic degradation of the NT• e.g. acetylcholinesterase

– 3. Uptake of the NT by neurons or glial cells (like astrocytes)

• done by neurotransmitter transporters

• e.g. NE, dopamine, serotonin

Neurotransmitters

1. small molecules: Acetylcholine (ACh)-All neuromuscular junctions use ACh – can only be excitatory-ACh also released at chemical synapses between two neurons

-can be excitatory or inhibitory – depends on location and the neurons involved

-inactivated by an enzyme acetylcholinesterase

-blockage of the ACh receptors by antibodies = myasthenia gravis - autoimmune disease that destroys these receptors and progressively destroys the NMJ-anticholinesterase drugs (inhibitors of acetylcholinesterase) prevent the breakdown of ACh and raise the level that can activate the still present receptors

2. Amino acids: glutamate & aspartate & GABA– most have powerful excitatory effects

– stimulate most excitatory neurons in the CNS (about ½ the neurons in the brain)

– GABA (gamma amino-butyric acid) is an inhibitory neurotransmitter for 1/3 of all brain synapses

• i.e. inhibits the generation of an action potential by the target neuron

Neurotransmitters

- Valium is a GABA agonist - enhances its inhibitory effect

Neurotransmitters3. Biogenic amines: modified amino acids

– catecholamines: norepinephrine (NE), epinephrine, dopamine, thyroxin • all derived from the amino acid tyrosine• NE - role in arousal, awakening, deep sleep, regulating mood• epinephrine (adrenaline) - flight or fight response• dopamine - emotional responses and pleasure, decreases skeletal muscle tone

– serotonin: derived from tryptophan• sensory perception, temperature regulation, mood control, appetite, sleep

induction• feeling of well being

Other types:a. ATP - released with NE from some neuronsb. Nitric oxide - formed on demand in the neuron then release (brief lifespan)

-role in memory and learning-produces vasodilation - Viagra enhances the effect of NO

Mimicking or Inhibiting NTs• Parkinsons - muscle stiffness due to degeneration of dopanergic nerves loss of dopamine in the brain loss of the brain’s control over skeletal muscles

•patients given L-Dopa (dopamine precursor)

• NT release can be enhanced or blocked•some amphetamines can promote dopamine and NE release•botulism causes paralysis through blockage of ACh release from motor neurons

• NT receptors can be blocked or activated•isoproterenol binds to epinephrine receptors

- used in asthma to mimic the effects of epinephrine• schizophrenia – caused by an excess of dopamine

•Zyprexa blocks dopamine and serotonin receptors -antagonizes the effects of serotonin and dopamine

• NT removal/uptake can be promoted or inhibited•cocaine: blocks transporters for dopamine reuptake•Prozac, Paxil: blocks transporters for serotonin reuptake

Neuropeptides

• widespread in the nervous system• excitatory and inhibitory• act as hormones elsewhere in the body

-Substance P -- enhances our perception of pain-opioid peptides: endorphins - release during stress, exercise

enkephalins - analgesics (200x stronger than morphine)

-pain-relieving effect by blocking the release of substance P

dynorphins - regulates pain and emotions

**acupuncture may produce loss of pain sensation because of release of opioid-like substances such as endorphins or dynorphins