Nervous System: General Principles

PA 481 C Anatomy & Physiology Tony Serino. Ph.D.

Nervous System

• Controls and/or modifies all other systems • Rapid response time • Usually short duration

Functional Areas

Divisions of the Nervous System

Nervous Tissue

• Non-excitable Tissue (Supportive cells) – Neuroglia –present in CNS – Schwann and Satellite cells –present in PNS • Neurons (excitable tissue) – Initiate and conduct electrical signals (action potentials)

Neuroglia (glial cells) •Form BBB •Regulate microenvironment •Pass on nutrients; get rid of waste Phagocytic, protective

Neuroglia •Line cavities •Create CSF Secrete myelin in CNS

PNS Supportive Cells • Schwann cells –secrete myelin in PNS • Satellite cells –surround neuron cell bodies in PNS

Neuron Anatomy

Axonal terminal Nerve ending Synaptic boutons Synaptic knobs

Functional Zones of a Neuron Receptor Zone Initial segment of Axon (trigger zone) Nerve endings Axon

Myelination • In PNS, a Schwann cell wraps and individual segment of a single axon • In the CNS, an oligodendrocyte performs the same function but can attach to more than one axon

Node of Ranvier: gaps in myelin sheath

Types of Neurons • Anatomical classification – Based on number of process projecting from cell body • Functional Classification – Based on location of neuron and direction of information flow

General Terms • Ganglia vs. Nuclei – Areas of densely packed nerve cell bodies – Ganglia are usually found in PNS – Nuclei are found in CNS • Nerve vs. nerve fiber – A nerve is a dissectible structure containing hundreds of axons – A nerve fiber is a single axon • CT sheaths covering peripheral nerves:

Nerve CT sheaths

Synapses • Areas where neurons communicate with other cells • Can be chemical (with neurotransmitters) or electrical (gap junctions)

Anatomy of Synapse (chemical) Neurotransmission ends when NT diffuses away, re-absorbed by presynaptic neuron, or NT metabolized (degraded) by enzymes in cleft

Neurotransmission • Electrical signal (action potential (AP)) descends axon to synaptic knob (nerve end) • Depolarization opens Ca ++ presynaptic membrane channels to open in • Triggers a number of synaptic vesicles to fuse with outer membrane • Dumps neurotransmitter (NT) into synaptic cleft • NT diffuses across cleft and binds to receptor on postsynaptic membrane • This leads to channels opening on postsynaptic membrane changing the membrane’s potential

Types of Anatomical Synapses

Membrane Potentials • Produced by the unequal distribution of ions across a selectively permeable membrane • The inside of the cell is called negative by convention • The intensity of the ion difference is expressed as voltage (measured in millivolts (mV))

Measuring Membrane Potentials

Resting Membrane Potential Parameters necessary to create a resting membrane potential: •A semi-permeable membrane •Distribution of ions across membrane •Presence of large non-diffusible anions in interior •Na-K pump (3 Na + out for every 2 K + in)

Gated Channel Proteins • Opening gate allows ions to travel into or out of the cell thereby changing the membrane potential • Can be controlled chemically or electrically

Chemically Gated Channel Protein

Voltage (electrically) Gated Channel Protein

Graded Potentials •Transient •Decremental •Most due to chemically Depolarization

Inside of cell becomes less negative

gated channels opening •Can be summated •May be excitatory or inhibitory Hyperpolarization

Inside of cell becomes more negative

Will only trigger AP if the threshold of the neuron is reached.

Summation •Temporal –a single axon fires repeatedly •Spatial –two or more axons fire simultaneously

Typical Receptor Zone Activity

Action Potentials • Wave-like, massive depolarization • Propagated down entire length of axon or muscle cell membrane • All or none • No summation possible • Due to opening of voltage gated channels and corresponding positive feedback cycle established – 1. Foot –graded potentials – 2. Uplimb –fast depolarization – 3. Downlimb –fast repolarization – 4. After Hyperpolarization –overshoot due to ion distribution

1 2 3 4

Events in Membrane during the AP

Foot Refractory Periods

AP Propagation The depolarization event triggers depolarization in the next area of the axon membrane; followed by repolarization. In this way the AP appears to move in a wave-like fashion over an unmyelinated axon membrane.

The depolarization event triggers depolarization in the next area of the axon membrane; followed by repolarization. In this way the AP appears to move in a wave-like fashion over an unmyelinated axon membrane.

AP propagation in unmyelinated axons

AP propagation in myelinated axons The AP appears to jump from node to node (saltatory conduction); the myelin sheath eliminates the need to depolarize the entire membrane.

Axonal Transport • Anterograde –towards synapse; flow of synaptic vesicles, mitochondria, etc.

• Retrograde –towards CB; recycled membrane vesicles, neuromodulators, etc.

Regeneration of Nerve Fibers •Damage to nerve tissue is serious because mature neurons are post-mitotic cells •If the soma of a damaged nerve remains intact, damage may be repaired •Regeneration involves coordinated activity among: – remove debris –form regeneration tube and secrete growth factors –regenerate damaged part

Response to Injury • Anterograde degeneration with some retrograde; phagocytic cells (from Schwann cells, microglia or monocytes) remove fragments of axon and myelin sheath • Cell body swells, nucleus moves peripherally • Loss of Nissl substance (chromatolysis) • In the PNS, some Schwann cells remain and form a tubular structure distal to injury; if gap or scarring is not great axon regeneration may occur with growth down tube • In the CNS, glial scar tissue seems to prevent regeneration If contact with tube is not established then no regeneration and a traumatic neuroma forms

Regeneration in PNS

Drug Intervention Possibilities A.

B.

C.

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E.

F.

G.

H.

Increase leakage and breakdown of NT from vesicles Agonize NT release Block NT release Inhibit NT synthesis Block NT uptake Block degradative enzymes in cleft Bind to post-synaptic receptor Stimulate or inhibit second messengers in post-synaptic cell