Nervous System: General Principles Anatomy & Physiology 1 Tony Serino. Ph.D. Biology Dept. Misericordia University

Nervous System Lecture Outline: Controls and/or modifies all other systems Rapid response time Usually short duration Lecture Outline: General anatomy and physiology of neurons CNS (Central Nervous System) PNS (Peripheral Nervous System)

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) Phagocytic,protective Form BBB Regulate microenvironment Pass on nutrients; get rid of waste

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

Internal Cell Body Structures

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 Functional 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 Nerve vs. nerve fiber 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: signal transduction

Neurotransmission Electrical signal (action potential (AP)) descends axon to synaptic knob (nerve end) Depolarization opens Ca++ channels to open in presynaptic membrane 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 gated channels opening Can be summated May be excitatory or inhibitory Depolarization Inside of cell becomes less negative Will only trigger AP if the threshold of the neuron is reached. Hyperpolarization Inside of cell becomes more negative

Graded potentials magnitude vary with stimulus strength

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 2 3 1 4

Events in Membrane during the AP

Refractory Periods Foot

AP propagation in unmyelinated axons 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 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 Schwann cells, Neurons and WBCs or microglia: 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

Drug Intervention Possibilities 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