Principles of Physiology Dr. Moattar Raza Rizvi Unit 9 Nervous System

The Nervous system has three major functions :  Sensory – monitors internal & external environment through presence of receptors  Integration – interpretation of sensory information (information processing); complex (higher order) functions  Motor – response to information processed through stimulation of effectors  muscle contraction  glandular secretion Nervous System

Two Anatomical Divisions – Central nervous system (CNS) Brain Spinal cord – Peripheral nervous system (PNS) All the neural tissue outside CNS Afferent division (sensory input) Efferent division (motor output) – Somatic nervous system – Autonomic nervous system General Organization of the nervous system

Brain & spinal cord General Organization of the nervous system This Slide Summary Important

Two types of neural cells in the nervous system:  Neurons - For processing, transfer, and storage of information  Neuroglia – For support, regulation & protection of neurons Histology of neural tissue

CNS neuroglia: astrocytes oligodendrocytes microglia ependymal cells PNS neuroglia: Schwann cells (neurolemmocytes) satellite cells Neuroglia (glial cells)

Astrocytes create supportive framework for neurons play a role in the establishment of a blood- brain chemical barrier. monitor & regulate interstitial fluid surrounding neurons secrete chemicals for embryological neuron formation stimulate the formation of scar tissue secondary to CNS injury CNS neuroglia

Oligodendrocytes create myelin sheath around axons of neurons in the CNS. Myelinated axons transmit impulses faster than unmyelinated axons Microglia “brain macrophages” phagocytize cellular wastes & pathogens Increase during infection of the CNS CNS neuroglia

Ependymal cells line ventricles of brain & central canal of spinal cord Cells found in the choroid plexus that secrete cerebrospinal fluid CNS neuroglia

Schwann cells surround all axons of neurons in the PNS creating a neurilemma around them. Neurilemma allows for potential regeneration of damaged axons creates myelin sheath around most axons of PNS Satellite cells support (structurally & functionally) groups of cell bodies of neurons within ganglia of the PNS PNS neuroglia

Neuron: Structure

Most axons of the nervous system are surrounded by a myelin sheath (myelinated axons) The presence of myelin speeds up the transmission of action potentials along the axon Myelin will get laid down in segments (internodes) along the axon, leaving unmyelinated gaps known as “nodes of Ranvier” Regions of the nervous system containing groupings of myelinated axons make up the “white matter” “gray matter” is mainly comprised of groups of neuron cell bodies, dendrites & synapses (connections between neurons) of Ranvier Neuron: Structure

Neurons of the nervous system tend to group together into organized bundles The axons of neurons are bundled together to form nerves in the PNS & tracts/pathways in the CNS. Since most axons are myelinated, these regions will look white in appearance (“white matter”) The cell bodies of neurons are clustered together into ganglia in the PNS & nuclei/centers in the CNS. These parts are not myelinated, therefore will look gray in appearance (“gray matter”) Anatomical organization of neurons

Figure 8-6 Neural Tissue Organization

Structural classification based on number of processes coming off of the cell body: Multipolar neuron multiple dendrites & single axon most common type Structural Classification of neurons

Bipolar neuron two processes coming off cell body – one dendrite & one axon only found in eye (retina), ear & nose (olfactory mucosa) Unipolar neuron single process coming off cell body, giving rise to dendrites (at one end) & axon (making up rest of process) Structural Classification of neurons

Functional classification based on type of information & direction of information transmission: Sensory (afferent) neurons – transmit sensory information from receptors of PNS towards the CNS most sensory neurons are unipolar, a few are bipolar Motor (efferent) neurons – transmit motor information from the CNS to effectors (muscles/glands/adipose tissue) in the periphery of the body all are multipolar Association (interneurons) – transmit information between neurons within the CNS; analyze inputs, coordinate outputs are the most common type of neuron (20 billion) are all multipolar (short dendrites and a long or short axon) Functional Classification of neurons

Reflex – a quick, unconscious response to a stimulus to protect or maintain homeostasis. e.g. stretch reflex, withdrawal reflex Reflex arc – neural pathway involved in the production of a reflex. Structures include: receptor sensory neuron integrating center (brain or spinal cord; may or may not involve association neurons (interneurons)) motor neuron effector Reflex arc

Stretch reflex - simplest type of reflex - no association neuron involved Reflex arc

Simplified Withdrawal reflex

Neurons at rest have an unequal distribution of charged ions inside/outside the cell, which are kept separate by the plasma membrane The sum of charges makes the outside of the membrane positive, & the inside of the membrane negative more Na+ ions outside more K+ ions inside large negatively charged proteins & phosphate ions inside Neuron Function

Because of the difference of ionic charges inside/outside the cell, the membrane of the resting neuron is “polarized” The difference in charges creates a potential electrical current across the membrane known as the “membrane potential (transmembrane potential)” Neuron Function

At rest, the transmembrane potential can also be referred to as the “resting membrane potential” (RMP) The RMP of a neuron = -70mV Neuron Function

Because Na + & K + can move through leakage channels of nerve cells, the resting membrane potential is maintained by the sodium-potassium exchange pump For ions to cross a cell membrane, they must go through transmembrane channels “leakage channels” – open all the time, allow for diffusion “gated channels” – open & close under specific circumstances (e.g. voltage changes) Neuron Function

This change in membrane potential is known as hyperpolarization If a stimulus opens gated K + channels, positive charges leave cell  membrane potential becomes more negative (-70mV  -90mV) When a stimulus is applied to a resting neuron, gated ion channels can open Neuron Function

When a stimulus causes Na + gates open, Na + diffuses into the cell This changes the electrical charge inside the cell membrane, bringing it away from its RMP of -70mV toward 0mV When the membrane potential (i.e. -70 mV) becomes less negative or in other words, approaches zero, the membrane is said to be depolarized This change in membrane potential is known as depolarization Neuron Function

If a stimulus only affects Na + gates at a specific site of the axon, the depolarization is small & localized only to that region of the cell. This is known as a graded potential But if the stimulus reaches a certain level (threshold level), voltage controlled Na + gates will begin to open in sequence along the length of the axon. The depolarization will propagate along the entire surface of the cell membrane This propagated change in the membrane potential is known as an action potential (nerve impulse) Neuron Function

APs involve the movement of Na + ions into the cell (causing depolarization of the membrane), followed immediately by K + ions moving out of the cell through voltage controlled K+ gates (causing repolarization of the membrane), that propagates down the length of the cell APs are due to voltage changes that open & close gated Na + & K + channels within excitable cells Only nerve cells & muscle cells are excitable, i.e. can generate APs. Once an AP begins, it will propagate down the entire cell at a constant & maximum rate. This is known as the “all or none” principle Action potentials

_ 70 _ Transmembrane potential (mV) Threshold Resting potential REFRACTORY PERIOD DEPOLARIZATIONREPOLARIZATION Local current Depolarization to threshold Sodium ions Activation of voltage- regulated sodium channels and rapid depolarization Potassium ions Inactivation of sodium channels and activation of voltage-regulated potassium channels The return to normal permeability and resting state Time (msec) 0123 Action Potential Conduction

Nerve cell at rest (RMP= -70mV) Stimulus applied to cell Na + gates at axon hillock cause localized depolarization (graded potential) If stimulus is strong enough, flow of Na + ions into cell reach threshold level triggering opening of voltage gated Na + channels & formation of an action potential (nerve impulse) Action Potential Conduction

this depolarization will spread to adjacent parts of the membrane, activating more voltage controlled Na + gates in succession Action Potential Conduction Once threshold is reached, Na + will quickly diffuse into the cell causing a rapid depolarization of the membrane (-70 mV  0 mV  +30 mV)

When the transmembrane potential reaches +30mV, Na+ gates will close & K + gates will open K + will quickly exit cell resulting in repolarization of membrane & return to resting state Action Potential Conduction

A. Action Potential B. Depolarization C. Repolarization D. Threshold E. Stimulus F. Resting state G. Refractory period

Continuous propagation (continuous conduction) Involves entire membrane surface Proceeds in series of small steps (slower) Occurs in unmyelinated axons (& in muscle cells) Propagation of an Action Potential

Saltatory propagation (saltatory conduction)  Involves patches of membrane exposed at nodes of Ranvier  Proceeds in series of large steps (faster)  Occurs in myelinated axons Propagation of an Action Potential

“Information” travels within the nervous system primarily in the form of propagated electrical signals known as action potentials. An action potential occurs due to a rapid change in membrane polarity (depolarization followed by repolarization) Depolarization is due to the influx of sodium ions (Na + ); repolarization is due to the efflux of potassium ions (K + ) “The Big Picture”

Most synapses within the nervous system are chemical synapses, & involve the release of a neurotransmitter Neurotransmitters are stored in vesicles that are located primarily in specialized portions of the Axon In order for neural control to occur, “information” must not only be conducted along nerve cells, but must also be transferred from one nerve cell to another across a synapse Conduction across synapses

The Structure of a Typical Synapse Synaptic knob is a part of a neuron comes in close proximity to another neuron at the synapse

Events at a Typical Synapse

An action potential arrives & depolarizes the synaptic knob (end bulb) Before repolarization can occur, Ca +2 gates open & Ca +2 diffuses into end bulb Repolarization occurs Events at a Typical Synapse

Ca +2 causes the synaptic vessicles to fuse with the end bulb membrane causing the exocytosis of the neurotransmitter Events at a Typical Synapse

The neurotransmitter diffuses across the synaptic cleft & binds to its receptors on the post synaptic membrane, causing an effect on the post synaptic cell Events at a Typical Synapse

The effect on the post synaptic neuron will depend on whether the neurotransmitter released is  Excitatory (e.g. Ach, norepinephrine (NE))  Inhibitory (e.g. seratonin, GABA) Excitatory neurotransmitters cause Na + gates to open in the post synaptic membrane  depolarization (impulse conduction) Inhibitory neurotransmitters cause K + or Cl - gates to open in the post synaptic cell  hyperpolarization (no impulse conduction) Synapse

 The effects of neurotransmitters on the post synaptic neurons are usually short lived because most neurotransmitters are rapidly removed from the synaptic cleft by enzymes or reuptake Synapse

The Central & Peripheral Nervous System

Meninges – Connective tissues that surround and protect the brain and spinal cord (CNS) Dura Mater – tough, fibrous outer layer; 2 layers thick around brain with creation of dural sinuses between layers; 1 layer around spinal cord with epidural space external Arachnoid – “spidery” web-like middle layer Pia Mater – delicate, thin inner layer; extension of pia mater (“filum terminale”) extends from tip of cord to coccyx to anchor cord in place Subarachnoid space – between arachnoid & pia mater; contains cerebral spinal fluid (CSF) The Central Nervous System

Cranial Meninges Pia mater: The membrane that supplies most of the blood to the brain

Spinal Meninges Most of the cerebrospinal fluid is found in the subarachnoid space

Begins at foramen magnum & ends at L2 vertebral level by forming conus medularis Made up of 31 spinal cord segments Has 2 thickened areas- - -cervical enlargement - supplies nerves to upper extremity -lumbar enlargement - supplies nerves to lower extremity ( conus medularis ) The Spinal Cord

Each spinal cord segment has a pair of dorsal roots with their associated dorsal root ganglia (DRG) ventral roots Dorsal root ganglion (DRG) Dorsal root Ventral root The Spinal Cord

Each dorsal root contains the axons of sensory neurons (unipolar neurons) Each dorsal root ganglion contains the cell bodies of these sensory neurons Each ventral root contains the axons of motor neurons (multipolar neurons whose cell bodies are within the cord) The Spinal Cord

The dorsal & ventral roots of each segment come together at the intervertebral foramen (IVF) to form a mixed spinal nerve The Spinal Cord

Part of the PNS Contain both motor & sensory fibers (“mixed nerve”) 31 pair of nerves – each nerve forms from union of dorsal/ventral root of spinal cord segment & exits between vertebra at IVF (intervertebral foramen) 8 pair cervical spinal nerves – 1 st cervical nerve exits between occipital bone & C1, 8 th cervical nerve exits the IVF between C7-T1 12 pair thoracic spinal nerves 5 pair lumbar nerves 5 pair sacral nerves 1 pair coccygeal nerves Spinal Nerves

Below the conus medularis, spinal nerves must angle downward (in the subarachnoid space) before exiting their IVF. These spinal nerves make up the cauda equina Spinal Nerves

Once formed, spinal nerves will branch The branches of most spinal nerves (comprised of axons) interweave to form nerve plexuses peripheral nerves then branch from the plexuses to provide motor & sensory innervation to specific areas of the body Spinal Nerves

 4 major plexuses  cervical  brachial  lumbar  sacral Nerve Plexus

 Cervical plexus (C1-C5)  gives off phrenic nerve  Brachial plexus (C5-T1)  gives off median, ulnar & radial nerve  Lumbar plexus (T12-L4)  gives off femoral nerve  Sacral plexus (L4-S4)  gives off sciatic nerve  No plexus forms between T2-T11 – intercostal nerves Spinal Nerve plexuses

Anterior median fissure Posterior median sulcus Lateral gray horn (T1-L2, S2- S4) - autonomic Anterior gray horn - motor Central canal Gray commissure Anterior column Lateral column Posterior column Posterior gray horn - sensory Sectional Anatomy of the Spinal cord

The spinal cord has a narrow central canal surrounded by “horns” of gray matter connected by a commissure. Gray matter horns contain sensory & motor nuclei ( groups of cell bodies ). Gray matter is surrounded by white matter “columns” which are made up of groups of myelinated axons creating organized ascending & descending tracts. “The Big Picture”

Groups of axons found in the white matter columns of the spinal cord that carry specific information Ascending tracts - carry sensory information up the spinal cord to areas of the brain Descending tracts – carry motor information from the brain down to specific levels of the spinal cord Ascending & descending tracts within the spinal cord are part of the sensory & motor pathways of the nervous system Tracts (Sensory & Motor Pathways)

 Spinothalamic tracts  carries poorly localized touch, pressure, pain & temperature from cutaneous receptors to the thalamus  from thalamus, some of this sensory info reaches primary sensory cortex of the cerebrum for “interpretation” & conscious awareness Ascending Tracts (sensory pathways)

 Posterior Columns  carries highly localized discriminative (fine) touch, vibration, conscious proprioception (position sense) to nucleus in medulla oblongata (M.O.)  from M.O., info travels along rest of pathway to thalamus & then to primary sensory cortex of cerebrum  Spinocerebellar  carries proprioceptive (positional) information to the cerebellum (unconscious awareness) Ascending Tracts (sensory pathways)

Posterior Column Pathway

 Corticospinal (pyramidal)  carries commands from primary motor cortex of cerebrum for conscious (voluntary) control of skeletal muscles.  most fibers cross in “pyramidal decussation” of medulla oblongata so that left cerebral cortex controls muscles on right side of body, & vice-versa.  Medial & lateral pathways  originate from a variety of brain nuclei & send signals to motor neurons in the spinal cord for (subconscious) coordination of skeletal muscle activity, maintenance of posture & muscle tone. Descending Tracts (motor pathways)

Corticospinal (pyramidal) Pathway

 Ascending & descending tracts are part of larger sensory & motor pathways  Sensory & motor information gets in/out of spinal cord via spinal nerves  These sensory & motor pathways include the afferent & efferent neurons of the PNS “The Big Picture”

 Brain stem  medulla oblongata (M.O.)  pons  midbrain  Diencephalon  thalamus  hypothalamus  epithalamus (pineal gland)  mamillary body  Cerebrum  Cerebellum m.o. pons midbrain T H P P Cerebrum Cerebellum M The Brain

 clear, colorless fluid formed by filtration of blood plasma by choroid plexuses within ventricles of the brain.  circulates through ventricles, into central canal of spinal cord & around brain & SC in subarachnoid space. Reabsorbed through arachnoid granulations into dural sinuses & then into bloodstream  functions in protection of CNS, support, nutrient supply, waste removal  sample of CSF can be taken at subarachnoid space inferior to the conus medularis by “lumbar puncture” (spinal tap) Cerebrospinal Fluid (CSF)

CSF Circulation

 Medulla oblongata  continuation of the SC above the foramen magnum  contains the pyramidal decussation  cranial nerve nuclei (XII-VIII (cochlear)  cardiac, vasomotor, & respiratory reflex centers  Pons  The region of the brain stem located between the midbrain and medulla oblongata  cranial nerve nuclei (VIII (vestibular) – V)  respiratory center The Brainstem

 Midbrain  cerebral peduncles – location of descending (motor) tracts  Corpora quadrigemina  superior colliculi – visual reflex centers  inferior colliculi – auditory reflex centers  cranial nerve nuclei (IV-III)  reticular formation – network of interconnected nuclei throughout brainstem responsible for maintaining states of consciousness (awake & aroused) The Brainstem Visual and auditory reflexes are centered in Midbrain

 Thalamus  surrounds 3 rd ventricle  2 halves connected by intermediate mass  comprised of sensory nuclei  The thalamus is a primary site of sensory integration The Diencephalon

 Hypothalamus  connects to pituitary gland via the infundibulum  has many important functions relating to maintaining homeostasis including:  integrating nervous & endocrine systems through control over pituitary gland  integration of ANS from visceral stimuli  hunger/satiety, thirst, body temp. regulation  hormone production (ADH, oxytocin)  subconscious coordination of motor responses associated with rage, pleasure, pain, sexual arousal  mamillary bodies – reflex centers associated with eating, & processing of olfactory sensations The Diencephalon

 Pineal gland  secretes Melatonin which helps regulate day-night cycles (circadian rhythm) The Diencephalon

 functionally related areas in cerebrum, thalamus & hypothalamus involved in  emotional states & behaviors  linking conscious areas of cerebrum with unconscious areas of brainstem  long term memory Limbic system

gyrus sulcus Cerebrum Higher thought processes for learning and memory are primarily in the cerebrum

Frontal lobe Central sulcus Parietal lobe Occipital lobe Parieto-occipital sulcus Temporal lobe Lateral sulcus (Insula is deep to lateral sulcus) Lobes of Cerebral Hemispheres The central sulcus in the cerebrum, separates the frontal from the parietal lobe.

insula Lobes of Cerebral Hemispheres

 Gray matter – outer cortex & inner nuclei (centers)  White matter – deep to cortex; comprised of fibers (pathways for communication):  association  commissural  projection Gray & White matter of cerebrum

 association fibers – connect gyri in same hemisphere  commissural fibers – connect gyri in opposite hemispheres (e.g. corpus callosum)  projection fibers – connect cerebrum with other parts of brain & spinal cord White matter of cerebrum

 Motor and Sensory areas  Association areas  Cerebral processing centers Functional areas of Cerebrum

primary motor cortex (precentral gyrus) primary sensory cortex (postcentral gyrus) Motor & Sensory

primary motor cortex (precentral gyrus) gustatory cortex primary sensory cortex (postcentral gyrus) auditory cortex olfactory cortex visual cortex Motor & Sensory

interpret incoming sensations; coordinate motor responses somatic motor association area (premotor cortex) visual association area Association areas

higher-order integrative centers may be unilateral general interpretive area (Wernike’s) –Lt hemisphere usually motor speech center (Broca’s) - Lt hemisphere usually Prefrontal cortex (bilat.) Cerebral Processing Centers

transverse fissure arbor vitae (white matter) folia (gray matter)  functions include control of skeletal muscles (unconscious) for balance, coordination & posture  Stores patterns of movement  links to brainstem by cerebellar peduncles  2 hemispheres connected by vermis  separated from cerebrum by transverse fissure  outer folia with inner arbor vitae The Cerebellum

 12 pairs of nerves (part of PNS) that connect to the brain; provide motor, sensory &/or autonomic (parasympathetic) function Cranial Nerves

I Olfactory – smell II Optic – sight III Oculomotor – motor to eye muscles; ANS for accommodation of lens & pupil constriction IV Trochlear – motor to one eye muscle V Trigeminal – motor to muscles of mastication, sensation to face & mouth VI Abducens – motor to one eye muscle VII Facial – motor to muscles of facial expression; taste; ANS to lacrimal & salivary glands VIII Vestibulocochlear – equilibrium & hearing IX Glossopharyngeal – swallowing, taste, ANS to salivary glands, sensory reception from monitoring of blood pressure in large arteries X Vagus – sensation from viscera; ANS visceral muscle movement (respiratory, digestive, cardiovascular systems) XI Accessory – motor to muscle of pharynx, SCM & Trapezius XII Hypoglossal – motor to tongue muscles Cranial Nerves (know #, name & basic function)

Motor regulation of smooth muscle, cardiac muscle, glands & adipose tissue (“visceral effectors”) through stimulation of “visceral efferent fibers”  Sympathetic (Σ) division – “fight or flight” response  Parasympathetic (PΣ) division – rest & repose (“conserve & restore”) response “dual innervation” – if organ receives both Σ & PΣ, one division excites, the other inhibits activity Autonomic Nervous System (ANS)

Somatic efferent: CNS Somatic motor neuron Skeletal muscle Visceral (autonomic) efferent: CNS Preganglionic neuronAutonomic ganglion Postganglionic neuron Visceral effector (myelinated, cholinergic) (excitatory synapse) unmyelinated, cholinergic or adrenergic) Effect may be excitatory or inhibitory depending on receptors Overview of ANS anatomy

 cell bodies of preganglionic neurons in lateral gray horns of spinal cord T1-L2 (“thoracolumbar division”)  axons of pregg Σ neurons travel to:  sympathetic chain ganglion, or  prevertebral (collateral) ganglion,&  adrenal medulla  pregg Σ fibers release Ach  postgg Σ neurons usually release norepinephrine (NE)  effects on visceral effectors usually excitatory but depend upon specific receptor present - alpha (α) or beta (β) Sympathetic

Preganglionic neuron Postganglionic neuron Visceral effector (myelinated, cholinergic) (excitatory synapse) unmyelinated Effect may be excitatory or inhibitory depending on receptors Lateral gray horns T1-L2 Σ Chain ganglion Prevertebral ganglion NE released (adrenergic) Alpha(α) or beta (β) Sympathetic

 cell bodies of preganglionic neurons found in cranial nerve nuclei (III, VII, IX, X) & lateral gray horns S2-S4 (“craniosacral division”)  pregg PΣ neurons travel to terminal ganglion (close to) or intramural ganglion (within wall) of effector  both pre & postganglionic PΣ fibers release Ach  effects on organ depend on specific receptor present (nicotinic or muscarinic) Parasympathetic

Preganglionic neuron Postganglionic neuron Visceral effector (myelinated, cholinergic) (excitatory synapse) unmyelinated Effect may be excitatory or inhibitory depending on receptors CNs (III, VII, IX, X) & Lateral gray horns S2- S4 Terminal ganglion Intramural ganglion Ach released (cholinergic) Nicotinic or Muscarinic Parasympathetic

Effects of Sympathetic Activation -“fight or flight” response (energy expenditure):  increased cardiovascular & respiratory activity  increased blood flow to brain (increased alertness), skeletal muscles, heart muscle, lungs  increased visual acuity (pupil dilation)  release of energy reserves from adipose, liver, & skeletal muscles  decrease in “non-essential” functions (ie. digestion)  release of Epi & NE from adrenal medullae to continue effects Activities of the ANS

Effects of Parasympathetic Activation -“rest & repose” response (conserve & restore energy):  decreased cardiovascular & respiratory activity  increased GI motility & enzyme secretion  pupil constriction  nutrient uptake & energy storage into adipose, liver, & skeletal muscles (glycogen) Activities of the ANS