Neuroscience Answers

498. neuroscience

Instructions        for         Fundamentals  of           Neuroscience   assignment        This       exam    is            intended                to           determine         how      well       you       have     grasped the       concepts             presented          in                class      and       supplemented by          your      readings.            You       can        use        your      notes,  textbooks,          journals,             and       your      handouts            to           help      you       answer these   questions.                Any       resource             except each     other!  All          questions           are        in           essay format,    and                are        intended            to           make    you       think     and       integrate            the        material              presented           to           you.      In           general,              answers              should be approximately           2             pages    in           length, but        remember,        quantity              is            not        necessarily         equivalent         to                quality!                                You       are        welcome,           if appropriate   and       utile,     to           include figures, drawings,           diagrams             etc,       but        be          wise!    And       all           material              from     published            sources should be          cited     appropriately.  Please  answer ALL        of           these   questions:                Question            1             –                            Question            2             –                            Question            3             –                  Question            4             –                            Question            5             –                            Question            6             –                                Question            7             –

  Question            1     

1)           Describe             three    ways     that       the        synthetic            activity  of           tyrosine              hydroxylase      can        be increased,    and       discuss differences        in           the                mechanism        and       the        time      frame   over      which   each     of           these   processes           works.  2) Describe        how      each     of           these   processes           links      changes              in           catecholamine  neurotransmission         to:                                                                                                                                                                                                                                                          a)           changes in          neuronal             activity of           catecholamine  neurons,             and                                                                                                                                                                                                                                                        b)           changes              in           the        internal               (body) or                external              (world) environment     3)           Discuss the        modulatory       effects of           catecholamines on          their     target   circuits,                and       how      each     of           the        TH-­‐regulatory processes            might   produce              different             functional           changes              in           these   modulatory                effects.

 Question            2   

It            is            well-­‐known    that       a             key        mechanism        by                which   drugs    increase              locomotor          activity (i.e.       cause   hyperactivity)   is            by          increasing            extracellular      dopamine.         In           preclinical           tests,    investigators     found   that       a                novel compound             (called  “hyper”)             increased           locomotor          activity in           mice.                     The       investigators     wanted               to           know    the        mechanism        by          which “hyper”  produced            this        behavioral          effect   and       asked   the        question,            “Is          the        increased                locomotor          activity induced               by          “hyper”               due to  an          action   of           the        novel     compound         to           increase              extracellular      dopamine          by          inhibiting            dopamine                uptake via         the        dopamine          transporter        in           vivo?”                  Based   on          material                covered              in           the        “Neurotransmitter         Transporter”     lectures,             and       your      supplemental readings, design  experiments     to           answer their     question.            Hint:                     Design your                answer as           if            you       were    writing a             short    research proposal           (therefore         your                answer should be          longer  than      a             few       pages). Your      research             proposal             should  have     the        following            sub-­‐ sections: 1.           Background       and       rationale             for         the                proposed           experiments     2.           Hypothesis        to           be          tested  3. Experiments to           be                carried out        4.           Expected            results 5.           Alternative        outcomes           if            you       do                obtain  the        expected            results 6. Literature      cited     Note:                   Providing            definitions                of           the        techniques        you       would  use        is            NOT      a             sufficient            answer.                                Use       your      training                in           neuroscience    and       pharmacology  to           provide                an          answer that       demonstrates  critical  thinking               and       appropriate experimental           design.

 Question            3  

You       have     created               a             transgenic          mouse which   expresses            an          inhibitory            Gi-­‐coupled DREADD    from     the        GFAP    promoter.          Long-­‐term                administration  of           CNO      from     P0-­‐P21              during  brain     development   leads    to           the reduction            in           the        density of           excitatory           synpases            in           CA1       of           the        hippocampus.   Given   that       astrocytes          are        known to           secrete many    proteins              which   regulate               synapse              formation,         you       suspect               that       there    is            an          activity-­‐dependent         protein that       is            secreted             by astrocytes    that       increases            synapse              density.

1) Design             an          experiment       to           prove   that       an          astrocyte-­‐secreted      factor   is            involved               in           the        phenotype        of           the        GFAP-­‐inhibitory           DREADD              mouse.

2) Assuming       that       you       have     proven that       a             secreted             factor   is            responsible,      design   experiments     to           identify               this        secreted             factor.

 

Question            4    

In           the        CNS,     myelin is            produced           by          oligodendrocytes.           Recently,            we         found   that       the brain-­‐derived        neurotrophic    factor   (BDNF) is            important           for         oligodendrocyte              development.  Propose              a             research                project to investigate   the        role       of           one       of           BDNF    in           neuron-­‐oligodendroglia                interaction,        myelination,      and       neural  circuit   development   in           the CNS.             Design a                research             project including             the        rationale             (or         hypothesis),      the        experimental                approaches       (methods           and techniques),             the        expected            results, and       the        possible               explanation       (their    roles     in           the        brain).

NAME:                  Question            5             You       have     found   a             novel    therapeutic       compound         and                are        concerned         that       it            may      have off-­‐target             effects in           the        hippocampus.   Provide               three    distinct approaches       (i.e.       behavioral          and       non-­‐ behavioral)                you would          use        to           evaluate             these   potentially         deleterious        effects. Please  include a             detailed              rationale,            experimental    design, and        potential             conclusions        for                each.

  Question            6            

 You       have     isolated               a             substance          from     fire        ants      that       produces            a             profound             mechanical        allodynia             when   injected              into mice.                           The       initial    pharmacology   studies demonstrate    the        following            properties:

1. Design a series   of           experiments     to           determine         the        site        of           action   of                this        substance:
2. Design additional experiments     to           determine         its          mechanism        of           action.

     Question            7             While   walking                through               the        woods, your      less-­‐than-­‐intelligent            hiking   partner                scrapes                the bottom        of           their     foot      (since   they      weren’t wearing               any        shoes), and       complains           of           massive,             throbbing           pain      an                hour     later.    While   you       consider              the        most     effective             treatment          for         addressing          this        form     of           nociception,      please  provide               your      friend with         an          accurate               assessment       of           the        biochemical       changes              occurring            in           the        primary afferent              neurons              innervating        the        affected tissue. Specifically,        identify               and                characterize      the        kinases,               kinase  targets,               neuronal             phenotype(s),  and       appropriate        treatment(s)     needed               to           diagnose             and       remedy               this        issue     for                your      intellectual         troglodyte          of           a             companion.       Please  cite references as           needed,               and       yes,       they      are        needed.