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THE NERVOUS SYSTEM: NEURAL TISSUE

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Title: THE NERVOUS SYSTEM: NEURAL TISSUE


1
  • THE NERVOUS SYSTEM NEURAL TISSUE

2
Nervous system functions
  • 1. sensory function
  • sensory receptors detect internal and external
    stimuli
  • information is sent to CNS via sensory (afferent)
    neurons within sensory nerves
  • 2. integrative function
  • integrates processing of information within the
    CNS
  • stores info and also makes decisions once info is
    processed
  • one important integrative function perception
  • processed by interneurons within the CNS
  • 90 of the neurons within the CNS are
    interneurons
  • 3. motor function
  • decision usually manifests itself as a motor
    command contraction of a muscle, secretion by a
    gland
  • motor commands travel along motor (efferent)
    neurons within motor nerves
  • commands are sent to effectors muscles and
    glands

3
Nervous system includes all neural tissue in body
  • about 3 of the total body weight
  • Central Nervous System
  • Brain and spinal cord (brain 100 billion
    neurons, SC 100 million neurons)
  • Peripheral Nervous System
  • All neural tissue outside CNS
  • includes the spinal and cranial nerves

4
A schematic of the vertebrate nervous system
Figure 21-6
5
Divisions of the nervous system
6
Cells in Nervous Tissue
  • Neurons
  • Neuroglia

7
Neuroglia (Glia)
  • glue
  • about half the volume of cells in the CNS
  • smaller than neurons
  • 5 to 50 times more numerous
  • do NOT generate electrical impulses
  • divide by mitosis
  • however, mature glial astrocytes may not be able
    to divide only precursors to glial populations
  • regulate the clearance of neurotransmitters
  • participate in neural development
  • provide growth factors and chemical cues for the
    development of neurons and their axonal processes
  • Two types in the PNS
  • Schwann cells
  • satellite cells
  • Four types in the CNS
  • Astrocytes
  • Oligodendrocytes
  • Microglia
  • Ependymal cells

8
Astrocytes
  • Largest of glial cells
  • Most numerous
  • Star shaped with many processes
  • projecting from the cell body
  • -two types protoplasmic, fibrous
  • -protoplasmic short branches, found in gray
    matter
  • -fibrous many long unbranched processes, found
  • in white matter
  • -processes make contact with the capillaries
    supplying the
  • CNS, the neurons of the CNS and the pia mater
    membrane
  • covering the brain and spinal cord
  • Help form and maintain blood-brain barrier
  • processes wrap around the blood capillaries and
    isolate the
  • neuron from the blood supply
  • -also secrete substances that maintain a unique
    permeability
  • for the endothelial cells that line these
    capillaries restricts
  • movement of substances out of the blood
  • Provide structural support for neurons
  • microfilaments within cytoskeleton

9
Oligodendrocytes
  • Each forms myelin sheath around the axons of
    neurons in CNS
  • Analogous to Schwann cells of PNS
  • Form a supportive network around CNS neurons
  • fewer processes than astrocytes
  • round or oval cell body

10
  • Medical Application Multiple sclerosis
  • -autoimmune condition - immune system attacks the
    central nervous system
  • refers to scars (scleroses better known as
    plaques or lesions) in the white matter of the
    brain and spinal cord
  • -leading to demyelination
  • -leads to immune destruction of oligodendrocytes
    and Schwann cells (mostly oligodendrocytes)
  • -onset usually occurs in young adults - more
    common in women
  • from 2 to150 cases per 100,000 US citizens
  • first described in 1868 by Jean-Martin Charcot
  • affects neuronal communication
  • causes genetics, infections, environmental risk
    factors
  • neurological symptoms vaired physical or
    cognitive
  • including changes in sensation, muscle weakness,
    muscle spasms, difficulties with coordination and
    balance, problems in speech or swallowing
    (dysphagia), visual problems, fatigue, acute or
    chronic pain,and bladder and bowel difficulties,
    cognitive impairment of varying degrees,
    emotional symptoms of depression or unstable mood
  • takes several forms discrete attacks (relapsing
    forms) or slowly accumulating over time
    (progressive form)

11
Microglia
  • few processes
  • derived from mesodermal cells
  • that also give rise to monocytes
  • and macrophages
  • Small cells found near blood vessels
  • 15 of the glial cells of the CNS
  • Phagocytic role - clear away dead cells
  • derived from hematopoietic stem cells
  • protect CNS from disease through phagocytosis of
    microbes
  • migrate to areas of injury where they clear away
    debris of
  • injured cells - may also kill healthy cells

12
Ependymal Cells
  • epithelial cells arranged in a
  • single layer
  • range in shape from cuboidal
  • to columnar
  • Form epithelial membrane lining cerebral cavities
    (ventricles) central canal - that contain CSF
  • Produce circulate the cerebrospinal fluid (CSF)
    found in these chambers
  • CSF colourless liquid that protects the brain
    and SC against
  • chemical physical injuries, carries
    oxygen, glucose and other necessary
  • chemicals from the blood to neurons and
    neuroglia

13
Brain tumors
  • Primary tumors
  • Tumors include astrocytoma, oligodendrogliomas,
    mixed gliomas, oligoastrocytomas,
    medulloblastoma, retinoblastoma, neuroblastoma,
    and teratoma.
  • Most primary brain tumors originate from glia
    (gliomas) such as astrocytes (astrocytomas),
    oligodendrocytes (oligodendrogliomas), or
    ependymal cells (ependymoma).
  • There are also mixed forms, with both an
    astrocytic and an oligodendroglial cell component
    - called mixed gliomas or oligoastrocytomas.
  • astrocytomas, oligondedrogliomas, or
    oligoastrocytomas may be benign or malignant.
  • Glioblastomas represents the most aggressive
    variety of malignant glioma.
  • pilocytic astrocytomas - affect mainly children
    and young adults- have a clinically favorable
    course and prognosis.
  • Secondary tumors and non-tumor lesions
  • Secondary or metastatic brain tumors originate
    from malignant tumors located primarily in other
    organs.
  • incidence is higher than that of primary brain
    tumors.
  • most frequent types of metastatic brain tumors
    originate in the lung, skin (malignant melanoma),
    kidney (hypernephroma), breast (breast
    carcinoma), and colon (colon carcinoma)

14
PNS Satellite Cells
  • Flat cells surrounding PNS axons
  • Support neurons in the PNS
  • help regulate the chemical environment
    surrounding the neurons

15
PNS Schwann Cells
  • each cell surrounds multiple unmyelinated PNS
    axons with a single layer of its plasma membrane
  • Each cell produces part of the myelin sheath
    surrounding an axon in the PNS
  • contributes regeneration of PNS axons

16
Neurons
  • what is the main defining characteristic of
    neurons?
  • have the property of electrical excitability -
    ability to produce
  • action potentials or impulses in response to
    stimuli

17
Representative Neuron
http//www.horton.ednet.ns.ca/staff/selig/Activiti
es/nervous/na1.htm
-neurofilaments or neurofibrils give cell shape
and support - bundles of intermediate
filaments -microtubules move material inside
cell -lipofuscin pigment clumps (harmless aging)
- yellowish brown -the processes that emerge from
the body of the neuron nerve fibers -two
kinds dendrites axons
1. cell body or soma (or perikaryon) -single
nucleus with prominent nucleolus (high synthetic
activity) -Nissl bodies -rough ER free
ribosomes for protein synthesis -proteins then
replace neuronal cellular components for growth
and repair of damaged axons in the PNS
18
Neurons
2. Cell processes dendrites (little trees) -
the receiving or input portion of the
neuron -short, tapering and highly
branched -surfaces specialized for contact with
other neurons -cytoplasm contains Nissl bodies
mitochondria
19
  • 3. Cell processes axons
  • Conduct impulses away from cell body-propagates
    nerve impulses to another neuron
  • Long, thin cylindrical process of cell
  • contains mitochondria, microtubules
    neurofibrils - NO ER/NO protein synth.
  • joins the soma at a cone-shaped elevation axon
    hillock
  • first part of the axon initial segment
  • most impulses arise at the junction of the axon
    hillock and initial segment trigger zone
  • cytoplasm axoplasm
  • plasma membrane axolemma
  • Side branches collaterals arise from the axon
  • axon and collaterals end in fine processes called
    axon terminals
  • Swollen tips called synaptic end bulbs contain
    vesicles filled with neurotransmitters

20
Axonal Transport
  • Cell body is location for most protein synthesis
  • neurotransmitters repair proteins
  • however the axon or axon terminals require
    proteins
  • e.g. neurotransmitters
  • Axonal transport system moves substances
  • slow axonal flow
  • movement of axoplasm in one direction only --
    away from cell body
  • movement at 1-5 mm per day
  • replenishes axoplasm in regenerating or maturing
    neurons
  • fast axonal flow
  • moves organelles materials along surface of
    microtubules
  • at 200-400 mm per day
  • transports material in either direction
  • for use in the terminals or for recycling in cell
    body

21
Axonal Transport Disease
  • toxins or pathogens travel within neurons by fast
    axonal transport route
  • tetanus (Clostridium tetani bacteria) toxin
    tetanospasmin
  • disrupts motor neurons causing painful muscle
    spasms
  • inhibits the release of GABA (inhibit muscle
    contraction)
  • lethal dose 2.5 ng per kg body weight (e.g. 70
    ng for 175 lbs)
  • bacteria enter the body through a laceration or
    puncture injury
  • incubation time of 3 to 21 days average 8 days
  • more serious if wound is in head or neck because
    of shorter transit time to the brain
  • closer to the CNS the wound shorter the
    incubation time
  • approximately 11 of reported tetanus cases have
    been fatal
  • Generalized tetanus - common type of tetanus,
    representing about 80 of cases.
  • first sign is trismus, or lockjaw, and the facial
    spasms called risus sardonicus, followed by
    stiffness of the neck, difficulty in swallowing,
    and rigidity of pectoral and calf muscles.
  • Other symptoms include elevated temperature,
    sweating, elevated blood pressure, and episodic
    rapid heart rate.
  • Spasms may occur frequently and last for several
    minutes with the body shaped into a
    characteristic form called opisthotonos. Spasms
    continue for 34 weeks, and complete recovery may
    take months.
  • Treatment
  • human tetanus immunoglobulin injection
  • tracheostomy and mechanical ventilation for 3 to
    4 weeks,
  • magnesium as an intravenous (IV) infusion, to
    prevent muscle spasm,
  • diazepam (known under the common name Valium) as
    a continuous IV infusion,

22
Structural Classification of Neurons
  • Based on number of processes found on cell body
  • multipolar several dendrites one axon
  • most common cell type in the brain and SC
  • bipolar neurons one main dendrite one axon
  • found in retina, inner ear olfactory
  • unipolar neurons one process only, sensory only
    (touch, stretch)
  • develops from a bipolar neuron in the embryo -
    axon and dendrite fuse and then branch into 2
    branches near the soma - both have the structure
    of axons (propagate APs) - the axon that projects
    toward the periphery dendrites

23
Structural Classification of Neurons
  • Named for histologist that first described them
    or their appearance
  • Purkinje cerebellum
  • Renshaw spinal cord
  • others are named for shapes
  • e.g. pyramidal cells

24
Functional Classification of Neurons
  • Sensory (afferent) neurons
  • transport sensory information from skin, muscles,
    joints, sense organs viscera to CNS
  • Motor (efferent) neurons
  • send motor nerve impulses to muscles glands
  • Interneurons (association/integrative) neurons
  • connect sensory to motor neurons
  • 90 of neurons in the body

25
Sensory Neurons
  • found in the Afferent division of PNS
  • Deliver sensory information from sensory
    receptors to CNS
  • many types in the CNS and PNS
  • free nerve endings bare dendrites associated
    with pain, itching, tickling, heat and some touch
    sensations
  • Exteroceptors located near or at body surface,
    provide information about external environment
  • Proprioceptors located in inner ear, joints,
    tendons and muscles, provide information about
    body position, muscle length and tension,
  • position of joints
  • Interoceptors located in blood vessels, visceral
    organs and NS
  • -provide information about
    internal environment
  • -most impulses are not perceived those
    that are,
  • are interpreted as pain or pressure

26
Sensory Neurons
  • Sensory receptors cont
  • mechanoreceptors detect pressure, provide
    sensations of touch, pressure,
  • vibration, proprioception, blood vessel stretch,
    hearing and equilibrium
  • thermoreceptors detect changes in temperature
  • nociceptors respond to stimuli resulting from
    damage (pain)
  • photoreceptors light
  • osmoreceptors detect changes in OP in body
    fluids
  • chemoreceptors detect chemicals in mouth
    (taste), nose (smell)
  • and body fluids

27
Motor Neurons
  • Efferent pathways
  • much more simplistic in classification
  • Stimulate peripheral structures
  • Somatic motor neurons
  • Innervate skeletal muscle
  • Visceral motor neurons
  • Innervate all other peripheral effectors
  • Preganglionic and postganglionic neurons

28
The Nerve Impulse
29
Terms to know
  • membrane potential electrical voltage
    difference measured across the membrane of a cell
  • resting membrane potential membrane potential
    of a neuron measured when it is unstimulated
  • results from the build-up of negative ions in the
    cytosol along the inside of the neurons PM
  • the outside of the PM becomes more positive
  • this difference in charge can be measured as
    potential energy measured in millivolts
  • polarization
  • depolarization
  • repolarization
  • hyperpolarization

30
The electric potential across an axonal membrane
can be measured
  • the differences in positive and
  • negative charges in and out
  • of the neuron can be measured by
  • electrodes resting membrane potential
  • -ranges from -40 to -90 mV

31
Ion Channels
  • ion channels in the PM of neurons and muscles
    contributes to their excitability
  • when open - ions move down their concentration
    gradients
  • channels possess gates to open and close them
  • two types gated and non-gated

1. Leakage (non-gated) or Resting channels are
always open, contribute to the resting
potential -nerve cells have more K than Na
leakage channels -as a result, membrane
permeability to K is higher -K leaks out of
cell - inside becomes more negative -K is then
pumped back in
2. Gated channels open and close in response to
a stimulus A. voltage-gated open in response to
change in voltage - participate in the AP B.
ligand-gated open close in response to
particular chemical stimuli (hormone,
neurotransmitter, ion) C. mechanically-gated
open with mechanical stimulation
32
The resting potential, generated mainly by open
resting, non-gated K channels
-the number of K channels dramatically
outnumbers that of Na -however, there are a few
Na leak channels along the axonal membrane
ECF
AXON
33
Graded potentials
  • local changes in membrane potential that occur in
    varying intensities (grades)
  • caused by the opening of ion channels in a region
    of the axonal membrane
  • usually ligand-gated or mechanically-gated
    channels
  • typically gated ion channels for sodium results
    in a slight depolarization graded potential
  • region that is being depolarized active area
  • stronger the triggering event stronger the
    graded potential that results
  • the stronger the trigger the more ion channels
    open, the greater the depolarization
  • spread by passive current flow
  • because a local area has begun to depolarize
    charge of this area changes
  • specifically the inside area gets more positive
    in relation to the surrounding areas that are at
    rest
  • the outer area becomes more negative in relation
    to the surrounding areas that are at rest
  • this produces a current that starts to spread to
    the surrounding areas depolarizing them
  • BUT they die over short distances
  • this current decreases as it travels further from
    the originating area

34
Action Potential
  • Resting membrane potential is -70mV
  • triggered when the membrane potential reaches a
    threshold usually -55 MV
  • if the graded potential change exceeds that of
    threshold Action Potential
  • Depolarization is the change from -70mV to 30 mV
  • Repolarization is the reversal from 30 mV back
    to -70 mV)
  • action potential nerve impulse
  • takes place in two stages depolarizing phase
    (more positive) and repolarizing phase (more
    negative - back toward resting potential)
  • followed by a hyperpolarizing phase or refractory
    period in which no new AP
  • can be generated

http//www.blackwellpublishing.com/matthews/channe
l.html
35
(No Transcript)
36
Local Anesthetics
  • Prevent opening of voltage-gated Na channels
  • Nerve impulses cannot pass the anesthetized
    region
  • Novocaine and lidocaine blocks nerve impulses
    along nerves that detect pain

37
Current flux through individual voltage-gated
channels determined by patch clamping
38
Continuous versus Saltatory Conduction
  • Continuous conduction (unmyelinated fibers)
  • An action potential spreads (propagates) over the
    surface of the axolemma

http//highered.mcgraw-hill.com/sites/0072437316/s
tudent_view0/chapter45/animations.html
39
Saltatory Conduction
  • Saltatory conduction
  • -depolarization only at nodes of Ranvier - areas
    along the axon that are unmyelinated and where
    there is a high density of voltage-gated ion
    channels
  • -current carried by ions flows through
    extracellular fluid from node to node

http//www.blackwellpublishing.com/matthews/action
p.html
40
Rate of Impulse Conduction
  • Properties of axon
  • Presence or absence of myelin sheath
  • Diameter of axon
  • The propagation speed of a nerve impulse is not
    related to stimulus strength.
  • Larger faster conduction
  • Myelin 5-7 X faster
  • larger, myelinated fibers conduct impulses faster
    due to size saltatory conduction

41
Myelination increases the velocity of impulse
conduction
Figure 21-15
42
Action Potentials in Nerve and Muscle
  • Entire muscle cell membrane versus only the axon
    of the neuron is involved
  • Resting membrane potential
  • nerve is -70mV
  • skeletal cardiac muscle is closer to -90mV
  • Duration
  • nerve impulse is 1/2 to 2 msec
  • muscle action potential lasts 1-5 msec for
    skeletal 10-300msec for cardiac smooth
  • Fastest nerve conduction velocity is 18 times
    faster than velocity over skeletal muscle fiber

43
Synaptic Communication
44
Synapse
  • Synapse
  • Site of intercellular communication between 2
    neurons or between a neuron and an effector (e.g.
    muscle)
  • Permits communication between neurons and other
    cells
  • Initiating neuron presynaptic neuron
  • Receiving neuron postsynaptic neuron
  • Most are axodendritic axon -gt dendrite
  • Some are axoaxonic axon gt axon
  • axon terminal swell to form synaptic end bulbs or
    form swollen bumps called varicosities
  • release of neurotransmitters from synaptic
    vesicles
  • multiple types of NTs can be found in one neuron
    type

http//www.lifesci.ucsb.edu/mcdougal/neurobehavio
r/modules_homework/lect3.dcr
45
Synapses
  • NTs will cause either and excitatory or
    inhibitory response
  • If the NT depolarizes the postsynaptic neuron
    excitatory
  • Often called an excitatory postsynaptic potential
    (EPSP)
  • Opening of sodium channels or other cation
    channels (inward)
  • Some NTs will cause hyperpolarization
    inhibitory
  • Often called an inhibitory postsynaptic potential
    (IPSP)
  • Opening of chloride channels (inward) or
    potassium channels (outward)
  • Neural activity depends on summation of all
    synaptic activity
  • Excitatory and inhibitory

46
Synapses
  • Electrical
  • Direct physical contact between cells required
  • Conducted through gap junctions
  • Two advantages over chemical synapses
  • 1. faster communication almost instantaneous
  • 2. synchronization between neurons or muscle
    fibers
  • e.g. retina, heart-beat

47
Synapses
  • Chemical
  • Membranes of pre and postsynaptic neurons do not
    touch
  • Synaptic cleft exists between the 2 neurons 20
    to 50 nm
  • the electrical impulse cannot travel across the
    cleft indirect method is required chemical
    messengers (neurotransmitters)
  • Most common type of synapse
  • The neurotransmitter induces a postsynaptic
    potential in the PS neuron type of AP
  • Communication in one direction only

http//www.blackwellpublishing.com/matthews/nmj.ht
ml
48
Chemical synapse
  • Is the conversion of an electrical signal
    (presynaptic) into a chemical signal back into an
    electrical signal (postsynaptic)
  • 1. nerve impulse arrives at presynaptic end bulbs
  • 2. fusion of synaptic vesicles to PM - role for
    calcium
  • 3. release of NTs
  • 4. opening of channels in PM of postsynaptic
    neuron (e.g. sodium)
  • 5. postsynaptic potential develops
    depolarization triggering of AP in postsynaptic
    neuron

49
Chemical synapse
  • propagation of AP at the target post-synaptic
    neuron usually involves opening of ligand-gated
    Na channels on the membrane of the post-synaptic
    neuron
  • binding of NT to a receptor on post-synaptic
    membrane
  • this receptor is the ligand-gated channel

50
Release of NTs from Synaptic end bulbs
Synaptic vesicles can be filled, exocytosed,
and recycled within a minute
  • -synaptic vesicles are filled with NTs
  • the vesicles move into proximity near the PM of
    the end bulb active zone
  • -upon receipt of AP into these bulbs -causes the
    opening of voltage-gated Ca2 channels
  • -the influx of calcium promotes the
  • docking of the synaptic vesicle with the PM and
    the exocytosis of their contents
  • -the synaptic vesicle components
  • are recycled for future use

51
Neurotransmitters
  • More than 100 identified
  • Some bind receptors and cause channels to open
  • Others bind receptors and result in a second
    messenger system
  • Results in either excitation or inhibition of the
    target
  • Removal of NTs
  • 1. Diffusion
  • move down concentration gradient
  • 2. Enzymatic degradation
  • e.g. acetylcholinesterase
  • 3/ Uptake by neurons or glia cells
  • neurotransmitter transporters
  • e.g. NE, epinephrine, dopamine, serotonin

52
  • 1. small molecules Acetylcholine (ACh)
  • All neuromuscular junctions use ACh
  • ACh also released at chemical synapses in the
    PNS and by some CNS neurons
  • Can be excitatory at some synapses and inhibitory
    at others
  • Inactivated by an enzyme acetylcholinesterase
  • Blockage of the ACh receptors by antibodies
    myasthenia gravis - autoimmune disease that
    destroys these receptors and progressively
    destroys the NMJ
  • Anticholinesterase drugs (inhibitors of
    acetylcholinesterase) prevent the breakdown of
    ACh and raise the level that can activate the
    still present receptors

53
Neurotransmitters
  • 2. Amino acids glutamate aspartate GABA
  • Powerful excitatory effects
  • Glutamate is the main excitatory neurotransmitter
    in the CNS
  • Stimulate most excitatory neurons in the CNS
    (about ½ the neurons in the brain)
  • Binding of glutamate to receptors opens calcium
    channels EPSP
  • GABA (gamma amino-butyric acid) produced from
    glutamate
  • is an inhibitory neurotransmitter for 1/3 of all
    brain synapses
  • drugs that affect GABA
  • alcohol
  • benzodiazapenes (valium)
  • barbituates (phenobarbitol)

54
GABA
  • GABA action is affected by a broad range of drugs
    called benzodiazepines
  • e.g. lorazepan Ativan
  • e.g. diazepam - Valium
  • Various uses hynoptic, sedative, anxiolytic,
    anticonvulsant, muscle relaxant, amnesic
  • Short lasting half life is less than 12 hours
  • hypnotic effects
  • insomnia
  • Long lasting half life is more than 24 hours
  • anxiolytic effects (anti-anxiety drug)
  • Acts to enhance GABA
  • GABA major inhibitory NT in the CNS
  • GABA binds to GABA receptors several types
  • Benzodiazepines bind and modulate the activity of
    the GABAA receptor which is the most prolific NT
    receptor in the brain
  • GABAA receptor is comprised of 5 protein subunits
  • One subunit is the alpha subunit
  • BZs bind to the alpha subunit only and increase
    its affinity for binding the GABA
    neurotransmitter
  • The GABAA receptor is a ligand-gated chloride
    channel
  • Binding of GABA increases the inward flow of
    chloride ions which hyperpolarizes the neuron and
    inhibits its ability to make a new action
    potential
  • Therefore BZs potentiate the inhibitory effects
    of GABA

55
Valium
  • top selling drug from 1969-1982
  • GABA agonist
  • Also decreases the synthesis of neurosteroid
    hormones (e.g. DHEA, progesterone) which may
    regulate emotional state
  • Acts on areas of the limbic system, the thalamus
    and the hypothalamus (anti-anxiety drug)
  • Metabolized by the liver into many metabolites
  • Gives rise to a biphasic half live of 1-2 days
    and 2-5 days!
  • Lipid-soluble and crosses the blood-brain barrier
    very easily
  • Stored in the heart, the muscle and the fat
  • Some drugs (barbituates), anti-depressants and
    alchohol can enhance its effect
  • Smoking can increase the elimination of valium
    and decrease its effects

56
Neurotransmitters
  • 3. Biogenic amines modified amino acids
  • catecholamines norepinephrine (NE), epinephrine,
    dopamine (tyrosine)
  • serotonin - concentrated in neurons found in the
    brain region raphe nucleus
  • derived from tryptophan
  • sensory perception, temperature regulation, mood
    control, appetite, sleep induction
  • feeling of well being
  • NE - role in arousal, awakening, deep sleep,
    regulating mood
  • epinephrine (adrenaline) - flight or fight
    response
  • dopamine - emotional responses and pleasure,
    decreases skeletal muscle tone

57
Dopamine
  • Involved in feelings of pleasure, strength
  • Also mediates skeletal muscle contraction
  • Neurotransmitters like dopamine, serotonin,
    glutamate, acetylcholine etc are secreted and
    then rapidly internalized by transporters in
    order to control their levels within the nervous
    system
  • Many drugs affect these transporters
  • Ritalin methylphenidate
  • Stimulant used to treat ADD, ADHD, narcolepsy amd
    chronic fatigue
  • 1954 initially prescribed for depression and
    narcolepsy
  • 1960 prescribed to children with ADD, ADHD
  • Reason?? Might be due to an imbalance in dopamine
  • Binds both dopamine and norepinephine
    transporters and inhibits their ability to take
    these NTs back up (keeps their levels high in the
    synapse)
  • Dopamine transporters (DAT) found in the PM of
    neurons (presynaptic)
  • Transports dopamine back into the neuron along
    with sodium ions (symporter)
  • This terminates the dopamine signal
  • Chloride ions are also required to enter the
    neuron to prevent depolarization
  • In adults these transporters regulate dopamine
    levels
  • Cocaine binds and inhibits DATs increasing
    dopamine in the synapse
  • Amphetamines binds amphetamine receptors on a
    neuron which causes the internalization of the
    DAT into the neuron increasing dopamine in the
    synapse

58
Other NT types
a. ATP - released with NE from some neurons b.
Nitric oxide - formed on demand in the neuron
then release (brief lifespan) -role in memory
and learning -produces vasodilation
59
Neuropeptides
  • widespread in both CNS and PNS
  • excitatory and inhibitory
  • act as hormones elsewhere in the body
  • -Substance P -- enhances our perception of pain
  • -opioid peptides endorphins - released during
    stress, exercise
  • -breaks down bradykinins (pain chemicals),
    boosts
  • the immune system and slows the growth of
    cancer
  • cells
  • -binds to mu-opioid receptors
  • -released by the neurons of the Hypothalamus
    and by
  • the cells of the pituitary
  • enkephalins - analgesics
  • -breaks down bradykinins (200x stronger than
    morphine)
  • -pain-relieving effect by blocking the
    release of
  • substance P
  • dynorphins - regulates pain and emotions

acupuncture may produce loss of pain sensation
because of release of opioid-like substances such
as endorphins or dynorphins
60
Morphine
  • Opiate analgesic
  • Principal agent in opium
  • Acts on the CNS
  • Acts on the GI tract decrease motility,
    decrease gastric secretion, decreases gastric
    empyting, increases fluid absorption
  • Other opiates heroin, codeine, thebaine
  • Acts on the neurons of the CNS (specifically the
    nucleus accumbens of the basal ganglia)
  • Binds to the mu-opioid receptor
  • Found throughout the brain especially in the
    posterior amygdala, the hypothalamus and thalams,
    the basal ganglia, the dorsal horn of the spinal
    cord and the trigeminal nerve
  • Relieves the inhibition of GABA release by
    presynaptic neurons
  • Also relieves the inhibition of dopamine release
    (addiction)
  • Binding activates the receptor and gives rise to
    analgesia, euporia, sedation, dependence and
    respiratory and BP depression.
  • Acts on the immune system! increase incidence
    of addiction in those that suffer from pneumonia,
    TB and HIV
  • Activates a type of immune cell called a
    dendritic cell decrease their activation of B
    cells decreased antibody production decrease
    immune function
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