The Nervous System

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The Nervous System

• Three Functions
• Sensory Input (Afferent) Affect
• Integration (Processing/Interpretation)
• Motor Output (Efferent) Effect

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Nervous System Organization

• Central Nervous System (CNS)
• Brain
• Spinal Cord
• Peripheral Nervous System (PNS)
• Afferent Division (Sensory)
• Efferent Division (Motor)

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PNS Afferent (Sensory)

• Somatic afferent fibers
• From skin, skeletal muscles and joints
• Visceral afferent fibers
• From internal organs (viscera)

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PNS Efferent (Motor)

• Somatic n.s. impulses to skeletal muscles
  a.k.a. voluntary ns
• Autonomic n.s. visceral motor fibers to smooth
  muscles, cardiac muscle, glands a.k.a.
  involuntary ns
• Sympathetic n.s. (fight or flight) stimulate
• Parasympathetic n.s. (rest and repose) inhibit

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NS Cell Makeup

• Neurons functional transmission cells
• Neuroglia Supporting cells that surround
  neurons a.k.a. glial cells or nerve glue
• CNS neuroglia
• Astrocytes
• Microglia
• Ependymal cells
• Oligodendrocytes
• PNS neuroglia
• Satellite cells
• Schwann cells

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Neuroglia

• Astrocytes - most abundant
• anchor to BVs, assist nutrient transfer
• glucose uptake, lactic acid delivery
• guide migrating young neurons
• synapse formation
• capillary permeability
• mop up K and recapture neurotransmitters

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Cont.

• Microglia thorny processes
• neuron health detectors transform to
  macrophages
• Ependymal cells wrapping
• squamous to columnar shape cilia in central
  cavities of the brain and spinal cord
• Permeable barrier between CSF and tissue fluid of
  CNS
• Oligodendrocytes
• wrap the thick nerve fibers of the CNS to make
  insulated coverings myelin sheaths

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Motor Neuron
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Neurons

• A.k.a. nerve cells
• Have extreme longevity up to 100 years!
• Essentially amitotic cannot divide/regen.
• Have high metabolic rate and need continuous
  glucose and oxygen
• Have two major anatomical structures
• Cell body
• Processes
• Axons
• Dendrites

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Axons

• Transmitting portion Action Potentials (APs)
  (conducting component)
• Anterograde movement
• Retrograde movement (abnormal w/ bacterial/viral
  agents)
• Profuse branching at terminal end (10,000 )
• Knob-like ends on the terminal branches
  (secretory component neurotransmitters - NTs)
• Axonal terminals (or)
• Synaptic knobs (or)
• Boutons

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Myelin Sheath Neurilemma

• Whitish fatty protein that is segmented
• Myelinated nerves conduct rapidly - larger
• Unmyelinated nerves conduct slowly- finer
• Neurilemma is the husk or external part of the
  Schwann cell
• Nodes of Ranvier

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Classification of Neurons

• Structural
• Multipolar
• Bipolar
• Unipolar
• Functional
• Sensory / Afferent
• Motor / Efferent
• Interneurons

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Neurophysiology

• Highly irritable
• Electrical impulse generated and conducted APs
• Voltage or potential difference measured in mV
  and generally a resting membrane of a neuron is
  -70mV
• Membrane Ions channels leakage/passive and
  gated/active
• Chemical (ligand) gated chemical stimuli
• Voltage-gated electrical stimuli
• Mechanically distortion stimuli

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Resting Membrane Potential
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Resting Membrane Potential

• - 70 mV across the membrane (varies - 40 to -
  90mV) when the membrane is polarized
• Negative sign means inside (cytoplasmic side) is
  negatively charged
• Charge is based on differences in ionic
  concentrations in intra and extra-cellular
  fluids, and differences in permeability
• K is the most important ion in generating
  membrane potential

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Membrane Potentials

• Changes in these is involved with receiving,
  integrating, and sending information.
• Caused by
• Anything altering ion permeability
• Anything altering ion concentrations on either
  side of the membrane.
• Produces either
• Graded potentials over short distances
• Action potentials over long distances

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Cont.

• Depolarization relative to resting it is less
  negative/more positive (closer to 0) on the
  inside of the neuron which increases the
  probability of producing a nerve impulse
• Hyperpolarization increased membrane potential,
  or more negative than resting potential which
  decreases the probabilility of a nerve impulse.

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Graded Potentials
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Action Potentials (APs)

• Principal form of neuron communication only in
  excitable membranes of neurons and muscle cells
• Brief reversal of membrane potential from -70 to
  30 mV
• Depolarization followed by repolarization phase
  and often a hyperpolarization period (msecs)
• APs are also called nerve impulses and only
  axons can generate one.
• Stimulus changes permeability via voltage-gated
  channels on the axon

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Generating APs

• Three overlapping membrane permeability changes
  by opening and closing active ion gates
• Resting State Voltage-gated Na/K channels
  closed
• Depolarizing phase Increase in Na permeability
  and reversal of membrane potential Na influx
  causes depolarization until threshold (-55 to
  -50mV)
• Repolarizing phase a) Decrease in Na
  permeability b) w/ increase in K permeability
• Hyperpolarization K permeability continues to
  produce undershoot

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Action Potential Resting State

• Na and K channels are closed
• Leakage accounts for small movements of Na and
  K
• Each Na channel has two voltage-regulated gates
• Activation gates closed in the resting state
• Inactivation gates open in the resting state

Figure 11.12.1
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Action Potential Depolarization Phase

• Na permeability increases membrane potential
  reverses
• Na gates are opened K gates are closed
• Threshold a critical level of depolarization
  (-55 to -50 mV)
• At threshold, depolarization becomes
  self-generating

Figure 11.12.2
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Action Potential Repolarization Phase

• Sodium inactivation gates close
• Membrane permeability to Na declines to resting
  levels
• As sodium gates close, voltage-sensitive K gates
  open
• K exits the cell and internal negativity of
  the resting neuron is restored

Figure 11.12.3
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Action Potential Hyperpolarization

• Potassium gates remain open, causing an excessive
  efflux of K
• This efflux causes hyperpolarization of the
  membrane (undershoot)
• The neuron is insensitive to stimulus and
  depolarization during this time

Figure 11.12.4
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Action Potential Role of the Sodium-Potassium
Pump

• Repolarization
• Restores the resting electrical conditions of the
  neuron
• Does not restore the resting ionic conditions
• Ionic redistribution back to resting conditions
  is restored by the sodium-potassium pump

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Propagation of APs

• Process in unmyelinated nerves
• Away from its point of origin toward axon
  terminals and then is self-propagating
• Ea. segment repolarizes - restores resting
  potential
• Process in myelinated nerves
• Saltatory conduction
• Propagation of nerve impulse is a better term to
  use than nerve impulse conduction

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Threshold All-or-None

• Not all local (graded) potentials lead to APs
• Reached when outward K inward Na movement
• At threshold either Na gates open with more Na
  entering or close with more K leaving and return
  to resting potential
• Stronger stimuli cause threshold to be reached
  and begins positive feedback cycle
• The AP either happens or it does not

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Stimulus Intensity

• APs are independent of stimulus strength,
  therefore the RATE of stimuli allow for the CNS
  to interpret intensity (i.e. more painful)

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Refractory Period

• When an AP is being generated it cant respond to
  another stimulus to create another AP the
  absolute refractory period
• The relative refractory period follows the
  absolute while Na gates are still closed and
  neuron is repolarizing.
• A very strong stimulus in the relative period CAN
  cause another AP to be initiated

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Conduction Velocity

• Axon diameter larger usually means faster, due
  to less resistance
• Degree of myelination
• a) Unmyelinated develop APs in adjoining
• segments of a neuron, thus are slow moving
• b) Myelinated are insulated by myelin and only
  allow current to pass at the nodes of Ranvier
  where voltage-gated channels are concentrated,
  thus are fast moving are termed saltatory
  conduction (Abnormal MS)

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Saltatory Conduction
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Multiple Sclerosis (MS)

• An autoimmune disease that mainly affects young
  adults
• Symptoms visual disturbances, weakness, loss of
  muscular control, and urinary incontinence
• Nerve fibers are severed and myelin sheaths in
  the CNS become nonfunctional scleroses
• Shunting and short-circuiting of nerve impulses
  occurs

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Multiple Sclerosis Treatment

• The advent of disease-modifying drugs including
  interferon beta-1a and -1b, Avonex, Betaseran,
  and Copazone
• Hold symptoms at bay
• Reduce complications
• Reduce disability

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Nerve Fiber Classification

• Group A large diameter myelinated found in
  somatic sensory and motor fibers of the skin
  muscles and joints (150 m/s)
• Group B lightly myelinated and intermediated
  diameter found in ANS motor fibers, visceral
  sensory fibers smaller somatic sensory fibers
  (15 m/s)
• Group C smallest and unmyelinated found in
  similar areas as B fibers (1 m/s)

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Imbalances

• Alcohol, sedatives and anesthetics all impair Na
  permeability no APs
• Cold and pressure interrupt blood flow and thus
  O2 delivery impairing AP generation and thus
  ability to conduct impulses

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Synapses

• Junction of one neuron (axonal terminals) with
  another neuron or neuromuscular junction
• Presynaptic is before and postsynaptic is after
• There may be as many as 1000-10,000 synapses with
  each neuron
• Two varieties
• Electrical sleep arousal, conscious perception,
  emotion, memory, and early embryonic nervous
  tissue
• Chemical (neurotransmitters)

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Chemical Synapses

• 1) Ca2 channels open in presynaptic axonal
  terminal and let in extracelluar Ca2
• 2) Neurotransmitter (NT) is released by Ca2
  causing vesicles of NT to empty into the cleft
• 3) NT binds with postsynaptic receptors
• 4) Ion channels open in postsynaptic membrane
  causing current locally to cause either
  excitation or inhibition
• More NT or longer lasting presence of NT
  greater response

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Postsynaptic Potentials

• APs are not generated, only locally graded
  depolarization events called excitatory or
  inhibitory postsynaptic potentials
• EPSP excitatory NT opens a single channel, with
  simultaneous flow of Na and K in both
  directions.
• IPSP inhibitory as NT binding causes
  hyperpolarization by ? K and/or Cl- entry

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Summation by Postsynaptic Neuron

• Single EPSP doesnt cause AP, but 1000s firing
  will or if a small number are firing, but rapidly
  it will
• Thus EPSP summate in one of two ways
• Temporal one or more presynaptic neurons firing
  rapidly add together
• Spatial multiple neurons simultaneously firing
  on one neuron
• IPSPs can also do this and inhibit it more
• Or they can do it together and the axon hillock
  will sort it all out

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Synaptic Modifications

• Synaptic Potentiation continuous use of a
  synapse enhances its PSPs related to ? Ca2 via
  NMDA receptors on postsynaptic side
• A.k.a. post-tetanic potentiation that increases
  the efficiency of NTs long duration seen in
  the hippocampus involved w/ memory/learning
• Presynaptic inhibition and neuromodulation- the
  pre side excitatory NT is inhibited by another
  neuron forming smaller EPSP
• Differs from postsynaptic inhibition that just ?
  excitability of post synaptic neuron

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Cont.

• Neuromodulation presynaptic event acting on
  postsynaptic membrane. Some of these influence
• Synthesis
• Release
• Degradation or . . .
• Reuptake of NTs at presynaptice neuron
• Others alter sensitivity of postsynaptic membrane
  to the NT act like hormones

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Neurotransmitters

• gt 50 different types with different NTs released
  at different stimulation frequencies
• ACh (acetylcholine) most plentiful, found at
  all neuromuscular junctions (NMJ) and some
  neurons of the ANS
• Contained in synaptic vesicles
• Degraded by Acetylcholinesterase or AChE on the
  postsynaptic membrane
• Converts it back into choline to be reused

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NT cont.

• Biogenic amines catecholamines like dopamine,
  norepinephrine (NE), epinephrine (EP), and the
  indolamines histamine serotonin
• Plays a significant role in emotional behaviors
• Biological clock
• Dopamine and NE are made from AA tyrosine, but
  cells that release each have only the enzymes
  needed to make the NT they release
• Same pathway used to create EP
• Serotonin made from AA tryptophan (sleep cycle)
• Histamine from AA histidine

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Synthesis of Catecholamines

• Enzymes present in the cell determine length of
  biosynthetic pathway
• Norepinephrine and dopamine are synthesized in
  axonal terminals
• Epinephrine is released by the adrenal medulla

Figure 11.21
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NT cont.

• Amino Acids GABA, glycine, glutamate, aspartate
  found only in CNS thus far
• Glutamate is excitatory in CNS important in
  learning and memory, but stroke victims suffer
  excitotoxicity and die
• GABA and Glycine are CNS spinal cord inhibitory
  decline in visual/auditory processing with age
  and are enhanced by alcohol TQZ
• Peptides neuropeptides include
• Substance P for pain mediation
• Endorphin, dynorphin enkephalins act as natural
  opiates to decrease pain sensation
• Enkephalins increase in pregnant women in labor
• Endorphins increase in competition runners
  high

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NT cont.

• Novel messengers include
• ATP produces fast excitatory response or slow
  second messengers provokes pain receptors
• Adenosine acts outside of cells as inhibitor in
  the brain
• Caffeine works by blocking those inhibitor
  receptors
• Dissolved gases
• Nitric oxide (NO) may be involved in retrograde
  messenger in memory and learning, smooth muscle
  relaxation (vasodilation), but toxic release in
  stroke victims causes damage
• Carbon monoxide (CO) may help mental alertness
  and acts similarly to NO

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Neurotransmitter Function Classification

• Excitatory vs. Inhibitory some groups do both
  and some NTs individually cause opposite actions
  (e.g. ACh excites skeletal m. and inhibits
  cardiac m.)
• Direct vs. Indirect open ion channels directly
  with rapid response (e.g. ACh) or promote
  longer-lasting effects w/ intracellular 2nd
  messengers G protein-linked receptors such as
  cyclic AMP or cyclic GMP using heightened Ca2
  influx/sensitivity (Ch.3 p.84)

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Neural Integration

• Neuronal pools some incoming signals are
  directly excitatory (discharge), while others are
  more peripheral and only facilitate possible
  excitation (or inhibition)

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Types of Circuits

• Diverging amplifying, and common in both
  sensory and motor circuits
• Converging concentrating, and are also common
  in sensory and motor circuits
• Oscillating reverberating causing positive
  feedback, seen in rhythmic cycles like
  sleep-wake, breathing, etc.
• Parallel after-discharge to common output cell
  at different times (15ms) seen in complex
  problem solving mental processes

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Spinal Reflex Arc
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Development of Neurons

• The nervous system originates from the neural
  tube and neural crest
• The neural tube becomes the CNS
• There is a three-phase process of
  differentiation
• Proliferation of cells needed for development
• Migration cells become amitotic and move
  externally
• Differentiation into neuroblasts

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Axonal Growth

• Guided by
• Scaffold laid down by older neurons
• Orienting glial fibers
• Release of nerve growth factor by astrocytes
• Neurotropins released by other neurons
• Repulsion guiding molecules
• Attractants released by target cells

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N-CAMs

• N-CAM nerve cell adhesion molecule
• Important in establishing neural pathways
• Without N-CAM, neural function is impaired
• Found in the membrane of the growth cone