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Nervous System Physiology

Lectures

2nd year English Module.

Ana-Maria Zagrean M.D., Ph.D.

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1. Organization of the Nervous system. Physiology of neuronsand glial cells. Excitability and ionic transport (Dec. 13)

2. Synaptic transmission in the nervous system.Neurotransmitters (Jan. 3)

3. Physiology of the neuro-muscular system (Jan. 10) .

4. Sensory transduction. Physiology of sight. Physiology of

hearing (Jan. 17).5. Physiology of the autonomic nervous system.

The hypothalamus. Integration of vital functions (Jan 24).

Nervous System Physiology

Lectures2nd year English Module.

Preliminary schedule.

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The nervous system

Human brain - most complex tissue in the body.

- mediates behavior ranging from simplemovements and sensory perception to learningand memory

- the organ of the mind

- capacity to thinkMany of the brain's functions are poorly understood.

While philosophers ponder the paradox of a person thinkingabout thinking, physiologists are trying to learn about learning.

Bruce R. Ransom in Boron & Boulpaep Medical Physiology

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Organization of the Nervous System: CNS, PNS & ANSNervous System: CNS, PNS & ANS

Central nervous system (CNS):

- brain (including cranial nerve II and retina) and spinal cord;

- covered by the meninges (pia mater, arachnoid, and dura mater);- special features: oligodendrocytes provide myelin; axons cannot regenerate

Peripheral nervous system (PNS):- parts of the nervous system that lie outside the dura mater;

- consists of peripheral ganglia (including cell bodies); sensoryreceptors; afferent & efferent peripheral portions of spinal nerves,cranial nerves (except CN II) and all peripheral portions of ANS.- special features: Schwann cells provide myelin; axons can regenerate

Autonomic nervous system (ANS):

-anatomically includes parts of CNS & PNS;-regulates & controls visceral functions through reflex arcs (visceralafferent/sensory neurons, control centers in the CNS that receive input,and visceral motor output).

- special feature: functionally distinct system

All elements of the nervous system work closely together in a wathat has no clear boundaries.

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Nervous System: structure

1) CNS (central nervous system):

brain

spinal cord

2) PNS (peripheral nervous system):

cranial nerves

spinal nerves

2 types of cells:

neuronsnon-neuronal cells

(previously considered just supporting cells)

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- ~1011 neurons in the human brain

and 10 x more neuroglia

Central nervous system (CNS):

Nerve cells

- Neurons have special shapes, physiological properties, andconnections (~1000 synapses/each neuron & other connectingmechanisms)

unique patterns of connectivity & regional specializationtremendous complexity of NS

- Neuroglial cells have variable structures that are suited for

their diverse functions; can function as signalling cells;provide a physiological environment for neurons

Nerve cells: neurons and neuroglial cells.

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The structure of a typical neuron

(1) cell body/ soma /perikaryon

(nucleus, ER, Golgi complex, mitochondria)(2) dendrites of various complexity: tapered, limitedlength, contain membrane rec. for neurotransmitters.

The dendrites & cell body are the main areas for

receiving information through the membrane receptorsthat bind and respond to the neurotransmitters releasedby neighboring cells.

(3) the axon:

- a cone-shaped axon hillock,- an initial segment/ the spike initiation zone

(unmyelinated region whereAP initiates)

- axon can extend for more than a meter, +/- myelin

(electrical insulation, fast impulse spread), highdensity of Na+ channels

- contain axoplasm, microtubules and microfilamentsthat confer structural stability and axonal transport

(4) the presynaptic terminals: rapid conversion of theneuron's electrical signal into a chemical / anothersignal in the postsynaptic membrane.

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Neuronal compartmentalization

Neurons, as polarized cells, have

distinct membrane protein at each of the

distinct domains of the plasma membr.

Smooth and rough ER & Golgi system

(are absent in the axon).

Protein synthesis (mainly in the cellbody, less in dendrites).

Role of mitochondria.

Anterograde and retrograde

axoplasmic transport of molecules in

vesicles along microtubules is mediated

by MAPs (microtubule-associated

proteins):kinesin for anterograde transport (always

move toward the plus end of microtubules,

away from the cell body)

and dynein for retrograde transport

(provides a mechanism for target-derivedgrowth factors, as NGF, to reach the nucleus

of a neuron where it can influence survival . Quantum content

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Features of Axoplasmic Transport

Transport

Type

Speed

(mm/day)Mechanism Material Transported

Fastanterograde

~ 400 Saltatory movementalong microtubules

by the motormolecule kinesin(ATP dependent)

MitochondriaVesicles containing

peptide and otherneurotransmitters, somedegradative enzymes

Fastretrograde

~200-300 Saltatory movementalong microtubulesby the motormolecule dynein (ATPdependent)

Degraded vesicularmembraneAbsorbed exogenousmaterial (toxins, viruses,growth factors)

Slowanterograde

~0.2-8 Not clear; possibly bymolecular motors

Cytoskeletal elements(e.g., neurofilament andmicrotubule subunits)

Soluble proteins ofintermediary metabolismActin

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Axoplasmic Transport

"signaling endosome"

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Cla

ssificationo

fneuronsbasedontheirstructure(Borone)

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Various forms of neurons.A, Pyramidal cell from the cerebral

cortex. B, Cerebellar Purkinje cell.

C, Sympathetic postganglionic neuron.

D, Spinal cord motor neuron.E, Dorsal root ganglion cell.

a, axon

Neuroglial cells of the central nervoussystem. A, Fibrous astrocyte (glial foot

processes in association with a capillary).

B, Protoplasmic astrocyte. C, Oligodendrocyte

(each process is responsible for the productioof one or more myelin sheath internodes

around central axons.D, Microglial cell.

E E end mal cells.

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Classification of Neurons based on their function

Types of neurons:

Sensory or afferent

Interneurons

Motor or efferent

Sensory/afferent nerves: messages from periphery to CNSMotor/efferent nerves: messages from CNS to peripheral

tissues.

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Classification of Neurons

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Classification of neurons based on the type of

information transmitted

Direction of information flow:

Afferent (sensory): neurons that transmit information into the CNS from sensorycells or sensory receptors outside the nervous system (dorsal root ganglion celland neurons in the sensory nucleus of the fifth cranial nerve).Efferent (motor): neurons that transmit information out of the CNS to muscles orsecretory cells (spinal motor neurons and motor neurons in the ANS).

The second category defines the anatomical distribution of the information flow.Visceral: neurons that transmit information to or from internal organs or regionsthat arise embryologically from the branchial arch (e.g., chemoreceptors of thecarotid body).Somatic: neurons that transmit information to or from all nonvisceral parts of thebody, including skin and muscle.

The third category, on the basis of the embryological origin of the structure beinginnervated.Special: neurons that transmit information to or from a "special" subset of visceralor somatic structures

- special visceral neurons: information travels to or from structures derived fromthe branchial arch region of the embryo (e.g., pharyngeal muscles)

- special somatic neurons, which handle only sensory information: the neuronsarise from the organs of special sense (e.g., retina, taste receptors, cochlea).

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Characteristics of Neurons

1) excitable

- respond to stimuli

- produce & conduct electrical impulses

- release chemical regulators2) amitotic- cannot divide by mitosis

3) long-lived

4) high metabolic rate

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Non-neuronal Cells

neuroglia

support & protect & nourish

& signal neurons

smaller & numerous

types:astrocytes

microglia

Schwann cells *

oligodendrocytes *

ependymal cells

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N l ll

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Non-neuronal cells:

Schwann cells and oligodendrocytes

(PNS) (CNS)

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Myelin

-Layers of lipid membrane of oligodendrocytes (CNS) or

Schwann cells (PNS)

-The signal that causes these glial cells to myelinate the axons

is an epidermal GF-like ligand (neuregulin), which derives

from the axon and whose potency is dependent of axonal size

(usually axons > 1microm in diameter are myelinated )

- voltage-gated Na+ channels are highly concentrated in the

nodes of Ranvier, and in low density beneath the sheath ofmyelin AP jump from one Ranvier to the next one

saltatory conduction

increased conduction velocity: 3-120 m/sec in myelinatedaxons comparing to 0.5-2 m/sec in unmyelinated axons

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Orthmann-Murphy, J. L. et al. J. Neurosci. 2007;27:13949-13957

Myelin, Oligodendrocyts and network of intercellularchannels between astrocytes and oligodendrocytes

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Neuro-vascular unit

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Neuron astroglia connections

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