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Physio Psyc

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Title: Physio Psyc


1
Physio Psyc
  • Ch.3

2
Sherrington
  • Sherrington deduced the properties of the synapse
    from his experiments on reflexes (an automatic
    muscular response to stimuli).
  • Reflex arc the circuit from sensory neuron to
    muscle response.

3
Reflex Arcs
  • Reflexes are slower than conduction along an axon
  • Several weak stimuli presented at slightly
    different times or location produce a stronger
    reflex than a single stimuli does.
  • Excitation of one set of muscles leads to a
    relaxation of others.

4
Temporal summation
  • Repeated stimuli within a brief time having a
    cumulative effect.

5
Temporal summation
  • Presynaptic neuron (the neuron that delivers the
    synaptic transmission)
  • Postsynaptic neuron (the neuron that receives the
    message).
  • Graded potentials Either depolarization
    (excitatory) or hyperpolarization (inhibitory) of
    the postsynaptic neuron.

6
EPSP
  • A graded depolarization is known as an excitatory
    postsynaptic potential (EPSP) and occurs when Na
    ions enter the postsynaptic neuron. EPSPs are
    not action potentials The EPSPs magnitude
    decreases as it moves along the membrane.

7
Spatial summation
  • Several synaptic inputs originating from separate
    locations exerting a cumulative effect on a
    postsynaptic neuron.

8
Inhibitory postsynaptic potential
  • (IPSP) A temporary hyperpolarization of a
    postsynaptic cell (this occurs when K leaves the
    cell or Cl- enters the cell after it is
    stimulated).

9
EPSP, IPSP APs
  • The probability of an action potential on a given
    neuron depends on the ration of EPSPs to IPSPS at
    a given moment.
  • Spontaneous firing rate The ability to produce
    action potentials without synaptic input (EPSPs
    and IPSPs increase or decrease the likelihood of
    firing action potentials).

10
Chemical Events at the Synapse
  • In most cases, synaptic transmission depends on
    chemical rather than electrical stimulation.
    This was demonstrated by Otto Loewis experiments
    where fluid from a stimulated frog heart was
    transferred to another heart. The fluid caused
    the new heart to react as if stimulated.

11
Major events at a synapse
  • Neurons synthesize chemicals called
    neurotransmitters.
  • Neurons transport the neurotransmitters to the
    axon terminal.
  • Action potentials travel down the axon. At the
    axon or presynaptic terminal, the action
    potentials cause calcium to enter the cell which
    leads to the release of neurotransmitters from
    the terminal into the synaptic cleft (space
    between the presynaptic and postsynaptic neuron).

12
Major events at a synapse
  • Neurotransmitters, once released into the
    synaptic cleft, attach to receptors and alter
    activity of the postsynaptic neuron.
  • The neurotransmitters will separate from their
    receptors and (in some cases) are converted into
    inactive chemicals.
  • In some cells, much of the released
    neurotransmitter is taken back into the
    presynaptic neuron for recycling. In some cells,
    empty vesicles are returned to the cell body.

13
Major events at a synapse
  • Although not conclusively proven, it is likely
    that some postsynaptic cells send negative
    feedback messages to slow further release of
    transmitter by the presynaptic cells

14
Neurotransmitters
  • Chemicals released by one neuron at the synapse
    and affect another neuron are neurotransmitters.

15
Neurotransmitters
  • Amino acids Acids containing an amine group
    (NH2).
  • Peptides Chains of amino acids. A long chain is
    called a polypeptide a still longer chain is a
    protein.
  • Acetylcholine A chemical similar to an amino
    acid, with the NH2 group replaced by an N(CH3)3
    group.

16
Neurotransmitters
  • Monoamines Neurotransmitters containing an
    amine group (NH2) formed by a metabolic change of
    an amino acid.
  • Purines Adenosine and several of its
    derivatives.
  • Gases Includes nitric oxide (NO) and possibly
    others.

17
Synthesis of neurotransmitters
  • Catecholamines (Dopamine, Epinephrine, and
    Norepinephrine Three closely related compounds
    containing a catechol and an amine group.
  • Choline is the precusor for acetylcholine.
    Choline is obtained from certain foods or made by
    the body from lecithin.
  • The amino acids phenylalanine and tyrosine are
    precursors for the catecholamines.
  • The amino acid tryptophan is the precursor for
    serotonin. The amount of tryptophan in the diet
    controls the levels of serotonin.

18
Transport of Neurotransmitters
  • Certain neurotransmitters, such as acetylcholine,
    are synthesized in the presynaptic terminal.
    However, larger neurotransmitters, like peptides,
    are synthesized in the cell body and transported
    down the axon to the terminal.
  • Transporting neurotransmitters from the cell body
    to the axon terminal can take hours or days in
    long axons.

19
Release and Diffusion of Transmitters
  • Neurotransmitters are stored in vesicles (tiny
    nearly spherical packets) in the presynaptic
    terminal. (Nitric oxide is an exception to this
    rule, as neurons do not store nitric oxide for
    future use). There are also substantial amounts
    of neurotransmitter outside the vesicles.

20
Release and Diffusion of Transmitters
  • When an action potential reaches the axon
    terminal, the depolarization causes
    voltage-dependent calcium gates to open. As
    calcium flows into the terminal, the neuron
    releases neurotransmitter into the synaptic cleft
    for 1-2 milliseconds. This process of
    neurotransmitter release is called exocytosis.

21
Release and Diffusion of Transmitters
  • After being released by the presynaptic neuron,
    the neurotransmitter diffuses across the synaptic
    cleft to the postsynaptic membrane where it will
    attach to receptors.
  • The brain uses dozens of neurotransmitters, but
    no single neuron releases them all.

22
Release and Diffusion of Transmitters
  • Each neuron releases the same combination of
    neurotransmitters at all branches of its axon.
  • A neuron may receive and respond to many
    neurotransmitters at different synapses.

23
Postsynaptic Cell
  • A neurotransmitter can have two types of effects
    when it attaches to the active site of the
    receptor ionotropic or metabotropic effects.

24
Postsynaptic Cell
  • Ionotropic effects Neurotransmitter attaches to
    the receptor causing the immediate opening of an
    ion gate (e.g., glutamate opens Na gates).

25
Postsynaptic Cell
  • Metabotropic effects Neurotransmitter attaches
    to a receptor and initiates a cascade of
    metabolic reactions. This process is slower and
    longer lasting than ionotropic effects.
    Specifically, when the neurotransmitter attaches
    to the receptor it alters the configuration of
    the rest of the receptor protein enabling a
    portion of the protein inside the neuron to react
    with other molecules.

26
Metabotropic effects
  • Activation of the receptor by the
    neurotransmitter leads to activation of
    G-proteins which are attached to the receptor.

27
Metabotropic effects
  • G-proteins A protein coupled to the
    energy-storing molecule, guanosine triphosphate
    (GTP).
  • Second messenger Chemicals that carry a message
    to different areas within a postsynaptic cell
    the activation of a G-protein inside a cell
    increases the amount of the second messenger.

28
Neuromodulators
  • Neurotransmitters, mainly the peptide
    neurotransmitters, that do not by themselves
    strongly excite or inhibit a neuron, instead they
    alter (modulate) the effects of a
    neurotransmitter.

29
Hormones
  • A hormone is a chemical that is secreted
    primarily by glands but also by other cells and
    conveyed by blood to other organs whose activity
    it influences.
  • Unlike neurotransmitters which are released
    directly to another neuron, hormones convey
    messages to any organ that can receive it.
  • Endocrine glands produce hormones.

30
Hormones
  • Protein hormones and peptide hormones are
    composed of chains of amino acids. Protein and
    peptide hormones bind to membrane receptors and
    activate a second messenger within the
    cellexactly the same process as at a
    metabotropic synapse. Some chemicals can act as
    both neurotransmitters and hormones such as
    epinephrine, norepinephrine, insulin and
    oxytocin.

31
Hormones
  • Hormones secreted by the brain control the
    secretion of other hormones.
  • The pituitary gland is attached to the
    hypothalamus and consists of two distinct glands,
    the anterior pituitary and the posterior
    pituitary.

32
Hormones
  • The posterior pituitary is composed of neural
    tissue like the hypothalamus. Two hormones,
    oxytocin and vasopressin (also known as
    antidiuretic hormone) are released from the
    posterior pituitary however both of these
    hormones are synthesized in the hypothalamus.

33
Hormones
  • The anterior pituitary is composed of glandular
    tissue and synthesizes and releases six hormones.
    The hypothalamus controls the release of these
    six hormones by secreting releasing hormones that
    stimulate or inhibit the release of the following
    hormones adrenocorticotropic hormone, thyroid
    stimulating hormone, prolactin, somatotropin
    (also known as growth hormone),
    follicle-stimulating hormone, luteinizing hormone.

34
Inactivation and Reuptake of Neurotransmitters
  • Neurotransmitters become inactive shortly after
    binding to postsynaptic receptors.
    Neurotransmitters are inactivated in different
    ways.
  • Acetylcholinesterase (AChE) Found in
    acetylcholine (ACh) synapses AChE quickly breaks
    down Ach after it releases from the postsynaptic
    receptor.

35
Inactivation and Reuptake of Neurotransmitters
  • After separation from postsynaptic receptor,
    serotonin and the catecholamines are taken up by
    the presynaptic neuron. This process is called
    reuptake it occurs through specialized proteins
    called transporters.
  • Some serotonin and catecholamine molecules are
    converted into inactive chemicals by enzymes such
    as COMT (converts catecholamines) and MAO
    (converts both catecholamines and serotonin).

36
Negative Feedback From the Postsynaptic Cell
  • Autoreceptors presynaptic receptors sensitive to
    the same neurotransmitter they release.
    Autoreceptors detect the amount of transmitter
    released and inhibit further synthesis and
    release after it reaches a certain level.

37
Negative Feedback From the Postsynaptic Cell
  • Postsynaptic neurons can respond to stimulation
    by releasing special chemicals that travel back
    to the presynaptic terminal where they inhibit
    further release of transmitter. Nitric oxide,
    anandamide, and 2-AG (sn-2 arachidoylglycerol)
    are three such chemicals.

38
Drugs and Synapses
  • Drugs can affect synapses by either blocking the
    effects (an antagonist) or mimicking (increasing)
    the effects (an agonist) of a neurotransmitter.
    A drug that is a mixed agonist-antagonist is an
    agonist for some behavioral effects or doses and
    an antagonist for others.

39
Drugs and Synapses
  • Drugs can influence synaptic activity in many
    ways, including altering synthesis of the
    neurotransmitter, disrupting the vesicles,
    increasing release, decreasing reuptake, blocking
    its breakdown into inactive chemicals, or
    directly simulating or blocking postsynaptic
    receptors.

40
Drugs and Synapes
  • Affinity How strongly the drug attaches to the
    receptor.
  • Efficacy The tendency of the drug to activate a
    receptor.

41
Drugs
  • Drugs are categorized by their predominant
    actions. For example, amphetamine and cocaine
    are stimulants, opiates are narcotics and LSD is
    a hallucinogen. Despite these differences,
    nearly all abused drugs directly or indirectly
    stimulate the release of dopamine in the nucleus
    accumbens (a small subcortical area rich in
    dopamine receptors).

42
Drugs
  • Stimulant drugs (e.g., amphetamines, cocaine,
    etc.) produce excitement, alertness, elevated
    mood, decreased fatigue, and sometimes motor
    activity. Each of these drugs increases activity
    at dopamine receptors, especially at D2, D3, and
    D4 receptors. Stimulant drugs are often highly
    addictive.

43
Stimulants
  • Amphetamine increases dopamine release from
    presynaptic terminals by reversing the direction
    of the dopamine transporter.
  • Cocaine blocks the reuptake of catecholamines and
    serotonin at the synapse. The behavioral effects
    of cocaine are believed to be mediated primarily
    by dopamine and secondarily by serotonin.
  • The effects of amphetamine and cocaine are both
    short-lived, because of the depletion of dopamine
    stores and tolerance.

44
Stimulants
  • Prolonged use of cocaine can cause long-term
    changes in brain metabolism and blood flow,
    increasing the risk of stroke, epilepsy, and
    memory impairments.
  • Methylphenidate (Ritalin) Stimulant currently
    prescribed for Attention Deficit Disorder (ADD)
    works like cocaine by blocking reuptake of
    dopamine at presynaptic terminals. The effects
    of methylphenidate are much longer lasting and
    less intense as compared to cocaine.

45
Stimulants
  • Methylenedioxymethamphetamine (MDMA or ecstasy)
    is a stimulant at low doses primarly increasing
    the levels of dopamine, however at higher doses
    it also releases serotonin and produces
    hallucinogenic effects.
  • MDMA destroys serotonin axons in laboratory
    animals. Deficits in serotonin synthesis and
    release have also been found in humans.

46
Nicotine
  • Compound found in tobacco. Stimulates the
    nicotinic receptor (a type of acetylcholine
    receptor) both in the central nervous system and
    neuromuscular junction of skeletal muscles can
    also increase dopamine release by attaching to
    neurons that release dopamine in the nucleus
    accumbens. Repeated use of nicotine leads to
    decreased sensitivity in nucleus accumbens cells
    responsible for reinforcement.

47
Opiates
  • Derived from (or similar to those derived from)
    the opium poppy. Common opiates include
    morphine, heroin, and methadone. Opiates have a
    net effect of increasing the release of dopamine
    by stimulating endorphin receptors. Opiates also
    decrease activity in the locus coeruleus which
    results in decreased response to stress and
    decreased memory storage.

48
Marijuana
  • Contains the chemical ?9-tetrahydrocannabionol
    (?9-THC) and other cannabinoids (chemicals
    related to ?9-THC) ?9-THC works by attaching to
    cannabinoid receptors. Anandamide and sn-2
    arachidonylglycerol (2-AG) are brain chemicals
    that bind to cannabinoid receptors.

49
Marijuana
  • Marijuana can be used medically to relieve pain
    or nausea, combat glaucoma (eye disorder) and to
    increase appetite. Common psychological effects
    of marijuana include intensification of sensory
    experience and the illusion that time is passing
    very slowly. Prolonged marijuana use is
    associated with impaired memory performance.

50
Hallucinogenics
  • Drugs that distort perception. Many
    hallucinogenic drugs like lysergic acid
    diethylamide (LSD) resemble serotonin and bind to
    serotonin type 2A (5-HT2A) receptors.
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