Aberrant(development(of(parvalbumin(inhibitory(circuits(underlies(cortical(dysfunction(in(Rett(Syndrome(Research(Director:(Dr.(Michela(Fagiolini((Rett(Syndrome((RTT)(is(a(leading(cause(of(mental(retardation(in(girls(caused(by(loss(of(function(mutations(to(the(methyl(CpG(binding(protein(2((MeCP2).(Much(recent(evidence(indicates(that(RTT(is(caused(by(abnormal(excitatory/inhibitory(balance(of(cortical(circuits.(Vision,(highly(regulated(by(inhibitory(activity,(first(develops(normally(in(RTT(animals,(but(begins(to(regress(after(postnatal(day(30((P30),(while(WT(acuity(remains(high.(Here(we(examine(parvalbumin((PV)(positive(neurons(in(the(binocular(zone(of(visual(cortex(in(MeCP2(knockout((KO)(and(wildtype((WT)(mice,(as(their(maturation(regulates(the(development(of(vision.(Overall(intensity(of(the(PV(stain(throughout(the(binocular(zone(was(increased(in(the(KO(animal(in(adulthood((P60)(compared(to(WT(littermates((p<0.01).(The(number(of(perisomatic(PV(puncta(onto(pyramidal(cells(was(also(increased(in(the(KO(animal((p<0.01)(at(P60.(Interestingly,(both(increased(puncta(and(PV(stain(intensity(were(present(as(early(as(P15,(before(the(regression(in(visual(function.(DarkVrearing(was(able(to(reduce(the(PV(stain(intensity(and(number(of(puncta(in(the(KO(animal(to(WT(levels(at(P60(and(improve(visual(acuity.(Heterozygous(deletion(of(the(NR2A(subunit(of(the(NMDA(receptor(also(rescued(the(RTT(phenotype,(reducing(the(number(of(puncta(and(PV(stain(intensity(starting(at(P15,(further(suggesting(that(an(imbalance(of(excitatory/inhibitory(transmission(underlies(the(behavioral(phenotype(and(aberrant(circuitry(in(RTT.(Taken(together,(these(experiments(suggest(an(underlying(pathology(in(the(maturation(of(cortical(inhibitory(circuits(of(RTT(mice,(which(is(rescued(through(proper(excitatory/inhibitory(balance(or(a(delay(in(maturation.(( (

Abnormalities(in(Neural(Structures(of(Attention(and(their(Relation(to(Impaired(Social(and(Role(Functioning(in(Schizophrenia(Research(Director:(Dr.(Christine(Hooker((Schizophrenia(is(a(disabling(mental(illness(characterized(by(deficits(in(brain(structure,(cognition,(and(social(functioning.(Although(each(of(these(impairments(has(been(investigated(individually,(few(studies(have(drawn(a(connection(between(the(underlying(neuroanatomical(abnormalities(in(schizophrenia(and(both(cognitive(performance(and(social(outcome.(The(present(research(sought(to(explore(this(unanswered(question,(thereby(addressing(a(significant(gap(in(the(schizophrenia(literature.(We(specifically(hypothesized(that(decreased(cortical(thickness(in(the(anterior(cingulate(cortex((ACC)(would(predict(impairments(in(sustained(attention(and(social(functioning(among(individuals(with(schizophrenia.(25(schizophrenia(patients(and(25(healthy(controls(matched(for(age,(education,(IQ,(and(gender(participated(in(the(study.(Subjects(underwent(structural(magnetic(resonance(imaging((MRI),(which(was(analyzed(using(surfaceVbased(morphometry(to(allow(for(subVmillimeter(calculation(of(regional(brain(volumes,(cortical(thickness,(surface(area,(and(sulcal(depth(and(curvature.(Sustained(attention(was(measured(using(the(identical(pairs(version(of(the(Continuous(Performance(Task((CPTVIP),(a(computerVbased(test(in(which(subjects(are(presented(with(a(rapid(series(of(2V,(3V,(or(4Vdigit(numbers(and(must(respond(with(a(mouse(click(only(when(the(same(number(appears(twice(in(sequence.(Social(functioning(was(evaluated(with(the(Social(Adjustment(ScaleVSelf(Report((SASVSR),(which(is(a(selfVreport(measure(that(evaluates(social(functioning(and(social(life(satisfaction.(We(found(decreased(ACC(cortical(thickness(and(increased(ACC(cortical(surface(area(among(schizophrenia(patients,(which(was(correlated(with(impaired(performance(on(the(CPTVIP(and(social(functioning(deficits(as(measured(by(the(SASVSR.(( (

Alterations(in(Excitatory(Input(to(Retinal(Ganglion(Cells(in(DBA/2J(Glaucoma(and(Optic(Nerve(Crush(Mouse(Models(Research(Director:(Dr.(Tatjana(Jakobs((Early(synapse(loss(has(been(implicated(in(many(neurodegenerative(diseases.(Molecular(components(involved(in(developmental(synapse(elimination(become(upregulated(in(early(glaucoma,(suggesting(that(synapses(may(be(lost(early(in(the(disease(as(well.(The(primary(objectives(of(this(thesis(include(determining(whether(synapse(loss(occurs(prior(to(whole(retinal(ganglion(cell((RGC)(loss(in(glaucoma(and,(if(so,(characterizing(the(spatial(manner(in(which(the(process(occurs.((In(order(to(determine(if(glaucoma(results(in(synapse(loss,(I(compared(the(expression(of(a(marker(for(excitatory(input(to(RGCs(in(healthy(retinas(with(that(found(in(retinas(of(two(mouse(models(of(glaucoma.(I(labeled(postsynaptic(densities(of(excitatory(input(to(RGCs(with(an(intravitreal(injection(of(an(adenoVassociated(virus(expressing(PSD95VGFP,(a(marker(of(excitatory(synaptic(input.(I(visualized(the(RGC(dendrites(along(which(synapses(lied(with(an(antibody(against(SMI32(neurofilament.(Through(a(quantitative(analysis(of(digitally(reconstructed(dendritic(trees,(I(find(that(the(linear(density(of(PSD95(puncta((number(of(puncta/length(of(dendritic(segment)(and(spacing(between(neighboring(puncta(are(relatively(uniform(throughout(the(dendritic(arbors(of(αVganglion(cells(in(retinas(of(healthy(mice.(I(also(find(that(linear(density(decreases(and(puncta(spacing(becomes(irregular(in(αVganglion(cells(from(retinas(of(DBA/2J(and(C57/BL6(mice(that(received(an(optic(nerve(crush.(Taken(together,(these(results(suggest(that(RGCs(lose(excitatory(synaptic(input(prior(to(cell(death(in(glaucoma.((( (

BTC(family(proteins(as(critical(controls(over(cortical(projection(neuron(development(Research(Director:(Dr.(Jeffrey(Macklis((The(mammalian(neocortex(is(composed(of(numerous(functionally(distinct(neuronal(subtypes.(Corticothalamic(projection(neurons((CThPN)(and(other(cortical(projection(neuron(subtype(populations(originate(from(progenitors(in(the(ventricular(and(subventricular(zones.(Certain(transcriptional(regulators(exercise(key(roles(in(the(precise(molecularVgenetic(programs(of(control(over(neuronal(subtype(specification.(These(regulators(will(both(control(the(development(of(the(cerebral(cortex(and(its(circuitry,(central(to(cognitive,(motor,(sensory,(and(associative(functions,(and(might(potentially(be(important(for(future(directed(differentiation(approaches(with(therapeutic(applications(for(degenerative(diseases.((In(this(thesis,(I(investigate(potential(roles(of(two(members(of(the(Groucho/Grg/BTC((BetaVTransducin(repeat(containing(Corepressor)(protein(family,(BTCVlike(and(BTC,(in(controlling(cortical(projection(neuron(differentiation(and(specification.(Members(of(the(Groucho/TLE((TransducinVlike(Enhancer(of(split)(family(of(transcriptional(corepressors(play(important(roles(in(vertebrate(neurogenesis,(hematopoiesis,(and(organogenesis.(BTC(family(members(generally(show(nonVoverlapping(expression(patterns(in(different(tissues(during(development,(suggesting(distinct(nonVredundant(roles(during(differentiation.((In(the(murine(neocortex,(BTCVlike(is(expressed(in(cortical(progenitors(and(layer(II/III(projection(neurons(while(BTC(is(expressed(primarily(in(layer(VI.(As(a(first(step(to(investigate(BTCVlike(and(BTC(roles(in(cortical(development,(I(determined(their(temporal(course(and(cellVtype(expression.(To(investigate(the(roles(of(BTCVlike(and(BTC,(I(used(BTCVlike(and(BTC(knockout(mouse(models,(and(applied(a(combination(of(experimental(approaches(to(study:(1)(potential(changes(in(neurogenesis(and(migration,(by(BrdUVpulse(birthdate(analysis,(2)(potential(changes(in(fate(specification,(by(immunocytochemical(labeling(or(in(situ(hybridization(for(established(markers,(and(by(axonal(retrograde(labeling(to(identify(projection(neuron(connectivity.(((These(studies(indicate(that(BTC(is(highly(expressed(by(CThPN(during(postmitotic(differentiation,(while(BTCVlike(is(expressed(by(progenitors(in(VZ/SVZ(and(by(postmitotic(neurons(in(the(upper(cortical(layers.(Loss(of(functional(BTC(protein(causes(a(striking(increase(in(the(number(of(subcerebral(projection(neurons((SCPN)(at(the(expense(of(CThPN,(though(it(does(not(alter(the(production(or(migration(of(CThPN.(In(the(BTC(null(cortex,(layer(VI(CThPN(abnormally(differentiate,(expressing(molecular,(morphological(and(hodological(characteristics(of(layer(V(SCPN.(Therefore,(BTC(is(required(for(the(appropriate(fate(specification(of(CThPN,(and(their(differentiation(from(other(closely(related(projection(neuron(subtypes.((Preliminary(results(from(loss(of(BTCVlike(function(studies(reveal(that(it(is(not(required(for(either(generation(of(neurons(from(progenitors(or(for(differentiation(of(upper(cortical(neurons.(However,(additional(experiments(are(required(to(investigate(potential(function(of(BTCVlike(in(cortical(development,(since(there(are(precedents(for(other(factors(potentially(compensating(for(its(gene(deletion.(I(am(currently(investigating(the(hypothesis(that(another(family(member(may(have(a(synergistic(effect(with(BTCVlike,(and(thus(may(be(able(to(compensate(for(the(absence(of(BTCVlike.((These(experiments(are(ongoing.((( (

Contribution(of(secretory(leukocyte(protease(inhibitor(to(the(generation(and(maintenance(of(inflammatory(pain,(The(Research(Director:(Dr.(Clifford(Woolf((Pain,(long(considered(one(of(the(cardinal(signs(of(inflammation,(is(a(dynamic(sensation(whose(complex(molecular(and(cellular(etiologies(are(not(completely(understood.(It(serves(in(most(cases(as(an(adaptive(mechanism(that(promotes(protective(behavior,(preventing(the(organism(from(interfering(with(its(inflammatory(and(wound(healing(processes.(We(show(that(secretory(leukocyte(protease(inhibitor((SLPI),(a(known(antiVinflammatory,(proVhealing(mediator,(also(generates(hypersensitivity(in(adult(mice.(Consistent(with(its(previously(described(roles,(SLPI(is(expressed(in(a(model(of(sterile(injuryVbased(inflammation(by(fibroblasts,(basal(keratinocytes(and(some(immune(cells,(with(peak(levels(reached(early(after(injury.(When(introduced(into(uninjured(mice,(its(recombinant(form((rSLPI)(produced(spontaneous(pain(as(well(as(mechanical(and(cold(hypersensitivity.(This(effect(was(doseVdependent(and(returned(to(baseline(by(24(hours.(Interestingly,(there(was(no(effect(on(heat(hypersensitivity.(Furthermore,(SLPIVmediated(pain(was(eliminated(in(vivo(by(the(addition(of(antibodies(to(the(SLPI(binding(partner(annexin(II,(a(protein(involved(in(shuttling(the(Nav1.8(sodium(ion(channel(to(the(neuronal(cell(surface.(This(channel(has(been(shown(to(play(an(integral(role(in(inflammatory(pain.(Together,(these(results(suggest(that(SLPI(promotes(a(balance(between(the(continuation(of(wound(healing(and(the(maintenance(of(inflammatory(pain(hypersensitivity,(likely(via(the(annexin(IIVNav1.8(pathway.(( (

Development(of(the(Implicit(Learning(Mechanism(in(Children:(An(fMRI(Study(Research(Director:(Dr.(Margaret(Sheridan((For(most(aspects(of(cognition(and(behavior,(differences(are(obvious(between(adults(and(children.(However,(implicit(memory(in(particular(is(a(cognitive(function(that(has(been(demonstrated(to(remain(consistent(with(age.(In(this(implicit(pathway,(encoding(can(be(incidental(or(unintentional,(and(the(retrieval(can(occur(outside(of(conscious(awareness.(Since(implicit(learning(is(associated(with(neural(structures(that(mature(early,(it(is(believed(to(have(a(different(developmental(time(course(than(explicit(learning.(It(is(believed(that(implicit(learning(is(carried(out(by(the(earlyVmaturing(basal(ganglia((BG),(which(then(provides(the(feedback(that(helps(to(‘train’(the(slower(to(mature,(explicit(learning(pathways(in(the(frontal(cortex,(specifically(the(prefrontal(cortex((PFC).(This(suggests(that(although(there(is(evidence(for(a(fast,(implicit(and(a(slow,(explicit(pathway,(there(is(a(good(amount(of(interaction(required(between(the(two(in(order(to(give(rise(to(the(most(significant(learning(results.(The(main(aim(of(this(study(was(to(understand(how(children(achieve(nonVverbalizable(implicit(learning(and(how(it(is(manifested(in(the(developing(brain.(To(do(so,(this(study(had(participants(aged(8(through(11(learn(associations(of(unique(button(presses(for(categories(of(visual(abstract(stimuli(they(were(presented(with(while(measuring(changes(in(fMRI(BOLD(signal.(It(is(anticipated(that(functional(changes(in(BG(and(PFC(will(arise,(with(compensatory(BG(recruitment(as(a(result(of(the(still(maturing(PFC,(providing(evidence(for(the(interaction(of(these(distinct(learning(pathways.(( (

Directed(Differentiation(of(Human(Pluripotent(Stem(Cells(into(Hypothalamic(Arcuate(Nucleus(Neurons(Research(Director:(Dr.(Chad(Cowan((The(arcuate(nucleus(of(the(hypothalamus(functions(as(a(key(regulator(of(hunger(and(satiety.(Study(of(these(cells(faces(significant(difficulty(due(to(the(low(quantities(of(hypothalamic(neuronal(subtypes(found(in(primary(samples.(To(better(study(these(neurons(in(humans,(my(project(seeks(to(establish(a(method(to(direct(the(differentiation(of(key(hypothalamic(neurons(from(human(pluripotent(stem(cells.(The(lentivirusV(induced(overexpression(of(BrnV2(in(iPSCVderived(neural(progenitor(cells(resulted(in(a(3.7Vfold(increase(in(endogenous(Nkx2.1(expression,(a(key(marker(of(the(developing(hypothalamus.(Overexpression(of(combinations(of(Nkx2.1,(Ascl1,(DLX2,(and(SFV1(resulted(in(increased(Nkx2.1(and(POMC,(a(key(hypothalamic(neuronal(subtype(implicated(in(satiety.(The(results(suggest(that(forced(overexpression(of(key(transcription(factors(may(push(cells(towards(a(hypothalamic(fate,(opening(the(door(for(the(generation(of(hypothalamic(neurons(in(vitro,(allowing(for(future(studies(sigh(as(highVthroughput(chemical(screens.(( (

Downstream(effects(of(mTOR(hyperactivation(in(Tsc2Qdeficient(neurons(increase(Eph(receptor(degradation(Research(Director:(Dr.(Mustafa(Sahin((Tuberous(Sclerosis(Complex((TSC)(is(a(disease(caused(by(mutations(in(either(TSC1(or(TSC2(genes(and(is(characterized(by(symptoms(such(as(the(formation(of(benign(tumors,(epileptic(seizures,(mental(retardation,(and(autism.(The(proteins(encoded(by(the(TSC1(and(TSC2(genes(form(a(dimer(complex(that(inhibits(the(mTOR(pathway.(Strikingly,(most(of(deficits(in(Tsc1(or(Tsc2(mutant(mice(are(reversible(by(rapamycin,(a(drug(that(directly(suppresses(mTOR,(suggesting(that(the(disease(is(a(result(of(mTOR(hyperVactivation.(In(physiological(context,(a(negative(feedback(loop(has(recently(been(uncovered(in(which(activated(mTOR(phosphorylates(and(stabilizes(the(adaptor(protein(Grb10,(which(in(turn(attenuates(the(PI3KVAkt(and(MAPK(signaling(upstream(of(mTOR.(However,(the(site(and(mechanism(of(Grb10Vmediated(regulation(have(not(been(fully(understood.(Interestingly,(Grb10(forms(a(constitutive(complex(with(NEDD4,(an(E3(ubiquitinase,(and(appears(to(recruit(specific(substrates(for(ubiquitination.(Among(the(known(substrates,(tyrosine(kinase(receptors(such(as(EGFR,(VEGFR,(Insulin(receptor(and(IGFV1R(are(downVregulated(by(NEDD4.((We(hypothesized(that(in(TscVdeficient(neurons,(constitutive(activation(of(mTOR(may(abnormally(activate(the(NEDD4/Grb10(mediated(ubiquination(of(Eph(receptors(that(play(fundamental(roles(in(axon(guidance(and(synapse(formation.(Our(results(show(decreased(EphB2(levels(in(Tsc2Vdeficient(neurons(compared(to(control(neurons(when(stimulated(with(ephrinB1VFc.(Surprisingly,(NEDD4(is(detected(in(EphB2(immunoprecipitates(from(Tsc2Vdeficient(neurons(but(not(from(the(control(neurons.(We(have(also(found(that(the(amount(of(Grb10(associated(with(NEDD4(is(increased(in(Tsc2Vdeficient(hippocampal(neurons(compared(to(the(control(cells.((Taken(together,(our(data(has(provided(a(linkage(between(mTOR(and(EphB(signaling,(which(might(contribute(to(the(axonal(phenotype(in(TscVdeficient(neurons.((( (

Dreaming(hinders(overnight(motor(skill(improvement(in(extended(learning(while(highQfrequency(spindle(activity(predicts(such(improvement(in(the(shortQterm(Research(Director:(Dr.(Robert(Stickgold((Dreaming(about(a(learned(task(has(been(shown(to(increase(performance(on(that(task,(thereby(suggesting(a(direct(link(between(dreaming(and(memory(processing.(However,(the(same(approach(has(not(been(as(rigorously(applied(to(dreams(following(REM(sleep(and(daytime(mentation(and(most(studies(do(not(focus(on(an(extended(period(of(time.(Therefore,(we(devised(a(10Vday,(atVhome(experiment(in(which(participants(played(an(audiovisual(motor(task((the(videogame(Dance(Dance(Revolution,(“DDR”),(recorded(their(performance(statistics(and(provided(mentation(reports(during(wake,(sleep(onset(and(REM.(We(have(demonstrated(that(NREM%(increases((while(REM%(decreases)(with(time(and(that(dreaming(about(the(learned(task(is(dependent(on(sleep(stage((occurring(most(frequently(at(sleep(onset)(and(is(predictive(of(overnight(increases(in(performance.(Meanwhile,(a(more(biological(approach(to(sleepVdependent(learning(leads(to(a(plethora(of(literature(that(addresses(the(role(of(the(sleep(spindle,(12V15(Hz(brain(wave(bursts(that(occur(mostly(during(stage(2(sleep.(Nonetheless,(what(remains(to(be(seen(is(whether(the(correlations(between(spindle(activity(and(learning(can(be(extended(from(simple(experiments(involving(finger(tapping(and(mirrorVtracing(tasks(to(the(complex(audiovisual(but(predominantly(motorVrelated(task(of(DDR.(Resultantly,(we(developed(an(overnight,(inVlab(experiment(in(which(EEG(was(used(to(record(spindle(activity.(Our(results(show(that(increases(in(task(performance(were(dependent(on(stage(2(sleep%(and(the(quantity(and(frequency(of(spindles.(In(addition,(initial(performance(on(the(task(was(found(to(be(predictive(of(subsequent(spindle(activity.((( (

Effect(of(Firing(State(on(Gap(Junction(Strength(in(the(Thalamic(Reticular(Nucleus,(The(Research(Director:(Dr.(Carole(Landisman((The(neurons(of(the(thalamic(reticular(nucleus((TRN)(have(two(different(firing(states:(tonic(firing,(associated(with(wakefulness,(and(burst(firing,(associated(with(synchronized(activity(during(deep(sleep(and(epilepsy.((Electrical(synapses,(because(of(their(prevalence(in(the(TRN(and(their(ability(to(synchronize(neuronal(activity,(may(be(involved(in(the(shift(between(these(two(firing(states.((This(thesis(analyzes(the(effect(of(firing(state(on(electrical(synapse(strength(in(the(TRN.((Hyperpolarizing(currents(during(dual,(wholeVcell(recordings(in(vitro(were(used(to(determine(the(coupling(strength(of(electrical(synapses(between(pairs(of(neighboring(TRN(neurons.((For(those(pairs(that(had(relatively(strong(electrical(connections,(a(low(calcium(extracellular(solution(was(washed(in(to(preference(the(cells(toward(burst(firing.((Electrical(synapse(strength(was(reassessed.((While(the(results(are(inconclusive(for(TRN(neurons(as(a(population,(some(individual(cell(pairs(did(significantly(change(coupling(strength(in(response(to(this(wash((both(increases(and(decreases(in(coupling(strength(were(observed.)((This(suggests(that,(while(further(research(is(necessary,(electrical(synapses(may(undergo(plasticity(in(response(to(a(change(in(firing(state.((Because(all(measurements(were(taken(with(hyperpolarizing(currents(rather(than(by(eliciting(action(potentials,(this(plasticity(could(be(involved(in(affecting(firing(patterns(within(a(particular(state(rather(than(resulting(from(them.(If(further(research(supports(these(data,(this(would(suggest(a(role(for(electrical(synapse(plasticity(resulting(from(a(change(in(firing(states(in(affecting(activity(patterns(in(the(TRN.(((( (

Emotional(Experiences(during(Motor(Task(Acquisition(and(their(Relationship(to(SleepQDependent(Learning,(TaskQRelated(Dreaming,(and(Sleep(Architecture(Research(Director:(Dr.(Robert(Stickgold((Although(the(function(of(sleep(continues(to(be(perplexing,(there(is(growing(interest(in(the(informationVconsolidation(theory(which(postulates(that(humans(sleep(in(order(to(consolidate(memory,(i.e.;(to(learn(by(processing(information(acquired(throughout(the(day(and(moving(it(from(short(to(longVterm(storage.(Research(in(this(field(has(suggested(that(memory(consolidation(may(be(dependent(on(sleep(stages,(and(in(particular(that(emotionally(salient(memories(may(be(processed(during(rapid(eye(movement((REM)(sleep.((This(has(important(implications(for(human(learning(behaviors(and(their(relationship(to(sleep(and(sleep(patterns,(as(evidence(suggests(that(memories(with(an(emotional(component(are(preferentially(selected(to(consolidation.(We(sought(to(explore(the(effects(of(adding(an(emotional(component(to(a(visual(motor(task(on(longVterm(sleep(architecture,(on(sleep(mentation,(and(on(task(acquisition(by(continuing(an(experiment(designed(by(another(researcher.(Moreover,(we(designed(an(experiment(to(assess(changes(in(sleeping(brainwaves(after(a(visual(motor(task(is(begun(and(to(explore(how(the(addition(of(an(emotional(component(affects(brainwaves(and(task(acquisition.(Results(not(available,(soon(to(follow.(( (

Epigenetic(Pathways(in(Zebrafish(Hair(Cell(Regeneration(Research(Director:(Dr.(ZhengVYi(Chen((Most(hearing(loss(is(caused(by(the(death(of(hair(cells,(the(sensory(neurons(in(the(inner(ear(that(convert(sound(waves(into(electrical(signals.(((Mammals(are(unable(to(regenerate(these(cells,(so(hearing(is(never(recovered(when(hair(cells(die.((The(goal(of(this(study(was(to(investigate(a(model(system(that(can(regenerate(hair(cells,(the(zebrafish,(in(order(to(identify(important(pathways(and(molecules(underlying(the(regeneration(process.(When(zebrafish(hair(cells(die,(the(cells(surrounding(them(are(reprogrammed(to(change(their(fate(and(become(new(hair(cells.(The(identification(of(necessary(pathways(in(the(zebrafish(was(carried(out(in(the(hopes(of(translating(the(findings(to(mammals(as(a(potential(new(therapy(for(deafness.(Thus,(in(this(study,(we(selected(several(molecular(pathways(involved(in(epigenetic(reprogramming(to(test(for(their(relative(importance(in(the(natural(process(of(zebrafish(hair(cell(regeneration(by(either(blocking(or(upregulating(them(with(administration(of(drugs.((We(hypothesized(that(blocking(a(necessary(or(important(pathway(would(lead(to(a(decreased(number(of(regenerated(hair(cells(72(hours(postVhair(cell(death,(the(time(needed(for(a(full(recovery(of(hair(cells(in(zebrafish.((Four(of(the(drugs(tested(–(Zebularine,(CIV994,(Panobinostat,(and(Garcinol(V(showed(significant(results,(suggesting(the(importance(the(histone(deacetyltransferase(and(DNA(methylation(pathways(in(which(they(act.((These(pathways(are(involved(in(changes(to(the(chromatin(that(allow(a(cell(to(reprogram(its(fate.((Activation(of(these(pathways(in(combination(with(other(therapies(could(potentially(induce(hair(cell(transdifferentiation(in(mammals,(reversing(hearing(loss.(((((( (

Evidence(for(Neuroplasticity(after(Neurocognitive(Training(in(Individuals(AtQRisk(for(Developing(Psychosis(Research(Director:(Dr.(Christine(Hooker((This(research(project(focused(on(the(neural(correlates(of(social(cognition(and(how(these(correspond(to(the(behavioral(deficits(that(are(symptomatic(of(individuals(at(risk(for(developing(schizophrenia(and(other(psychotic(disorders.(The(project’s(objective(was(to(assess(the(potential(of(neurocognitive(training,(as(a(protective(treatment,(for(harnessing(neural(plasticity(in(individuals(atVrisk(for(developing(psychosis.(It(was(expected(that(neurocognitive(training(would(stimulate(brain(functioning(and(structure(in(our(test(population(of(atVrisk(individuals,(corresponding(to(improvements(in(their(social(cognition(and,(thus,(their(reported(symptoms(and(behavioral(performance.(To(test(this,(my(investigation(utilized(structural(neuroimaging(to(analyze(grey(matter(volume(changes(in(our(test(population(after(the(completion(of(the(neurocognitive(training(period.(To(gauge(the(efficacy(of(neurocognitive(training(in(improving(the(symptom(outlook(and(disease(prognosis(of(the(test(population,(their(brain(volume(changes(were(compared(with(volume(changes(in(a(demographically(and(clinicallyVmatched(population(that(received(placebo(training.(In(comparison(to(the(placebo(population,(the(test(population(exhibited(modest(volume(increases(in(the(right(superior(temporal(lobe(and(left(amygdala(volumes(and(these(increases(correlated(with(participants’(improvements(on(behavioral(measures(of(social(and(global(cognition(completed(before(and(after(the(test(training.(The(results(indicate(the(viability(of(neurocognitive(training(as(an(effective(treatment(for(the(behavioral(symptoms(of(atVrisk(individuals(and(suggest(the(treatment’s(potential(for(diminishing(the(risk(of(psychosis(onset(in(this(population.(( (

Examining(the(Role(of(the(muQcrystallin(gene(Crym(in(oxidative(stress(metabolism(and(connectivity(in(the(CNS(Research(Director:(Dr.(Paola(Arlotta((The(mammalian(cerebral(cortex(contains(a(staggering(variety(of(projection(neurons,(and(a(number(of(studies(have(recently(identified(genes(that(may(lead(to(their(individual(specification(during(development.(For(the(clinically(relevant(subpopulation(of(corticospinal(motor(neurons((CSMN),(which(degenerate(in(patients(with(Amyotrophic(Lateral(Sclerosis((ALS),(a(series(of(genes(have(been(identified(whose(expression(is(restricted(to(CSMN(and(excluded(from(closely(related(populations.(One(of(these(genes(was(Crym,(a(novel(gene(that(codes(for(the(protein(muVcrystallin(and(is(expressed(at(increasing(levels(during(embryonic(development.(In(the(presence(of(the(important(metabolic(molecule(nicotinamide(adenine(dinucleotide(phosphate((NADPH),(Crym(dimerizes(to(bind(two(molecules(of(thyroid(hormone((T3)(in(the(cytoplasm.(Since(both(NADPH(and(T3(are(two(molecules(known(to(regulate(oxidative(stress(pathways(and(neuronal(development,(we(hypothesized(that(Crym(might(provide(CSMN(with(some(protection(against(oxidative(stress(during(critical(periods(of(development.(Here,(we(first(provide(a(detailed(expression(profile(of(Crym(in(the(cortex.(Next,(we(compare(the(behavioral(and(physical(response(of(Crym+/+,(Crym+/V(and(CrymV/V(mice(to(induced(oxidative(stress.(Finally,(we(determine(whether(Crym’s(role(during(cortical(development(relates(to(synaptogenesis(by(comparing(the(number(of(synapses(in(the(hippocampuses(of(Crym+/+,(Crym+/V(and(CrymV/V.(Through(these(experiments,(we(can(begin(to(elucidate(the(precise(role(that(Crym(plays(during(cortical(development(and(how(this(gene(might(be(linked(to(the(degeneration(observed(in(ALS.( (

Exploring(the(brain's(potential(for(an(immune(response(to(metastases(Research(Director:(Dr.(Lois(Lampson((Recently,(immunotherapy(for(primary(brain(tumors(is(showing(promise(as(a(therapeutic(technique.(Since(primary(brain(tumors(and(metastases(differ(in(their(inherent(biologies,(it(is(important(in(developing(immunotherapeutic(techniques(to(examine(and(understand(the(potential(for(an(immune(response(in(the(brain.((A(key(portion(of(this(study(was(devoted(to(examining(the(background(literature(on(immunotherapy(for(primary(brain(tumors(and(metastases.(Following(this(understanding(of(the(immune(response(to(primary(brain(tumors,(sections(of(rat(brains(that(had(been(stained(for(metastatic(breast(cancer(tumor(foci(and(immune(responding(cells((T(cells,(monocytes,(and(macrophages/microglia)(were(examined(under(a(microscope.(Locations(of(the(foci(and(immune(responding(cells(were(noted(and(compared(in(an(effort(to(understand(if(the(pattern(of(immune(responding(cells(relative(to(metastatic(tumor(foci(is(different(for(various(regions(of(the(brain.((The(study(found(that(the(brain(has(an(inherent(potential(for(immune(response(to(metastases.(Immune(responding(cells(are(observed(in(relation(to(metastatic(tumor(foci(in(all(regions(of(the(brain,(although(more(research(is(needed(to(determine(there(are(regional(differences(with(regards(to(the(robustness(of(the(immune(response.(This(work(will(provide(a(foundation(for(continued(research(on(the(interactions(of(breast(cancer(metastases(with(the(potential(for(an(immune(response(in(the(brain(that(will(be(crucial(to(developing(more(effective(immunotherapeutic(treatments(for(metastases.((((( (

How(Abstractions(Affect(Image(Discrimination(in(Monkeys(Research(Director:(Dr.(Margaret(Livingstone((Humans(and(monkeys(have(the(ability(to(recognize(images(that(have(been(subtly(abstracted.(Visual(abstractions(drastically(change(an(image(on(the(pixel(level(yet(maintain(elements(of(the(image’s(original(content.(The(principal(objective(of(this(thesis(was(to(explore(the(neurobiological(mechanisms(underlying(visual(perception(of(abstracted(images.(I(developed(a(prototypeVbased(behavioral(touchscreen(task(for(three(adult(Rhesus(monkeys((Macaca(mulatta)(to(test(the(monkeys’(ability(to(discriminate(between(images(that(had(been(abstracted(along(combinations(of(three(different(dimensions:(color,(acuity,(and(orientation.(The(abstractions(were(design(to(help(study(the(direct(effect(of(visual(manipulation(on(behavioral(response.(Each(image(set(was(observed(to(be(of(similar(difficulty(for(the(monkeys.(I(found(that(the(variables(of(image(familiarity,(color(differences,(and(form(differences(had(no(significant(effect(on(behavioral(response.(Most(surprising(was(the(result(that(the(combined(manipulation(of(color(and(acuity(yielded(the(lowest(recognition(percentages.(The(color(and(acuity(abstractions(independently(yielded(the(highest(scores,(but(when(the(abstractions(were(combined,(the(score(plummeted.(Color(and(acuity(are(both(functions(of(the(parvocellular(pathway;(these(results(suggest(that(there(is(an(additive(effect(of(visual(abstractions(that(tamper(with(the(performance(of(the(same(visual(pathway.(The(findings(indicate(a(direct(relationship(between(visual(manipulation(and(behavioral(recognition,(which(could(be(explained(by(the(rudimentary(differences(between(magnocellular(and(parvocellular(ganglion(cells.(( (

Identifying(Neural(Substrates(of(GSKQ3(Involved(in(Neuroplasticity(and(Mood(Regulation(Research(Director:(Dr.(Stephen(J.(Haggarty((Bipolar(disorder(is(a(devastating(illness(whose(symptoms(are(often(difficult(to(manage(and(treat.((The(persistence(of(two(phases—manic(and(depressive—makes(the(disorder(even(more(challenging(and(life(threatening,(often(necessitating(a(complex(treatment(plan.((Lithium(has(been(the(firstVline(treatment(for(bipolar(disorder(since(its(efficacy(was(discovered(over(50(years(ago.((However,(lithium’s(mechanism(of(action(is(still(unknown,(and(many(patients(are(unresponsive(to(the(drug.((Research(in(recent(years(has(highlighted(the(significance(of(the(enzyme(Glycogen(Synthase(Kinase(3,(or(GSKV3,(in(mood(regulation.((More(specifically,(a(proteomics(isotopic(labeling(experiment(identified(various(proteins(whose(regulation(and(expression(was(affected(by(GSKV3.((Using(Western(Blotting(and(immunofluorescent(imaging,(we(studied(the(effects(of(lithium,(a(direct(and(indirect(GSKV3(inhibitor,(and(the(novel(compound(CHIR99021,(a(direct(GSKV3(inhibitor,(on(induced(pluripotent(stem((iPS)(cellVderived(neural(progenitor(cells(and(neurons.((Overall,(we(observed(an(increase(in(VGF((not(an(acronym,(involved(in(organismal(homeostasis(and(energy(balance)(in(response(to(lithium(but(not(CHIR99021.((Our(results(also(demonstrated(an(increase(in(PHLPP1((Ph(domain(and(Leucine(rich(repeat(protein(phosphatase,(involved(in(cell(survival)(in(response(to(CHIR99021(but(not(lithium.((Furthermore,(we(discovered(a(complete,(consistent(disappearance(of(phosphoVCRMP2((Collapsin(Response(Mediator(Protein(2,(involved(in(neuronal(differentiation(and(axonal(guidance)(in(response(to(both(drugs.((We(expanded(on(our(potential(discovery(of(phosphoVCRMP2(as(a(reliable(reporter(of(GSKV3(inhibition,(and(developed(an(assay(to(screen(for(novel(GSKV3(inhibitors.( (

Improving(Detection(of(fMRIQbased(Brain(Activity(in(Addiction(Networks:(Methods(and(Application(to(Nicotine(Addiction(Research(Director:(Dr.(Anne(Eden(Evins((Introduction:(Nicotine(addiction(is(a(worldwide(problem(with(farVreaching(public(health(and(economic(consequences.(To(improve(development(of(effective(treatments,(we(need(novel(neuroimaging(methods(for(understanding(the(neurobiology(of(nicotine(addiction.(The(goal(of(this(study(is(to(identify(the(best(fMRI(statistical(analysis(approach(for(mapping(out(key(brain(regions(involved(in(nicotine(addiction.(Methods:(BloodVoxygen(level(dependent(fMRI((BOLD(fMRI)(data(were(collected(from(14(nicotineVdependent(smokers(during(passive(viewing(of(neutral(and(smokingVrelated(visual(cues.(Three(statistical(analysis(approaches(–Statistical(and(Parametric(Mapping(Version(8((SPM8)(with(segmentation(only,(SPM8(with(Diffeomorphic(Anatomical(Registration(Through(Exponentiated(Lie(Algebra((DARTEL),(and(Advanced(Normalization(Tools((ANTs)(were(used(to(preVprocess(and(analyze(the(data.(SPM8(with(segmentation(only/DARTEL(averaged(individual(brain(images(to(produce(a(standard(template,(while(ANTs(used(a(more(refined(process(to(create(a(highly(localized(standard(template.(Results:(Although(ANTs(required(more(execution(time,(occupied(larger(memory(and(was(used(with(other(software,(all(methods(allowed(for(quick(numerical(and(visual(assessment(of(results.(ANTs(generated(greater(fMRI(activation(intensities(in(small,(variable,(subcortical(regions(implicated(in(the(visual(smoking(cueVinduced(craving(phase(of(nicotine(addiction.(Functional(connectivity(analyses(are(pending(resolution(of(technical(issues.(Discussion:(Overall,(ANTs(is(a(superior(fMRI(statistical(analysis(strategy(to(SPM8(with(segmentation(only/DARTEL.(While(SPM8(is(the(more(widely(used(statistical(analysis(strategy(across(the(neuroimaging(community,(our(study(suggests(that(future(fMRI(research(should(look(to(ANTs(as(the(new(gold(standard(approach(for(statistical(analysis.(( (

Influence(of(the(Median(Raphe(on(Hippocampal(Theta(Oscillations(as(Revealed(by(Electrophysiology(and(Optogenetics,(The(Research(Director:(Dr.(Bernat(Kocsis((The(hippocampus(of(the(mammalian(brain(is(known(to(play(a(crucial(role(in(processes(such(as(long(and(shortVterm(memory(consolidation(and(spatial(navigation.((Theta(rhythms(generated(within(the(hippocampus(indicate(increased(hippocampal(activity(linked(to(longVterm(potentiation(and(learning.((Two(major(brain(structures,(the(median(raphe(nucleus((MRN)(and(reticular(pontis(oralis((RPO),(modulate(hippocampal(theta(oscillations(through(regulation(of(key(neurotransmitters(like(serotonin,(GABA,(and(glutamate.((While(the(RPO,(a(major(glutamatergic(synchronizing(structure,(and(the(MRN,(a(major(serotonergic(desynchronizing(structure,(have(been(known(to(affect(hippocampal(theta(rhythms,(their(influences(have(only(been(studied(independently(of(each(other.((((The(purpose(of(this(study(was(to(delineate(the(influence(of(the(RPO(and(MRN(on(hippocampal(theta(oscillation(through(simultaneous(stimulation(of(the(left(and(right(RPO(structures(and(then(simultaneous(stimulation(of(the(MRN(and(RPO.((Experiments(were(performed(on(a(total(of(19(rats.((In(9(rats,(electrodes(were(surgically(inserted(into(either(the(left(and(right(RPO(or(the(right(RPO(and(MRN,(and(a(recording(electrode(was(inserted(into(hippocampus(between(the(dentate(gyrus(and(the(CA1.((Brain(wave(oscillations(were(recorded(using(electroencephalography(technology((EEG)(and(analyzed(using(DasyLab(7.0.(Results(showed(that(dual(stimulation(of(the(left(and(right(RPO(produced(a(power(dependent(increase(in(theta(frequency(relative(single(RPO(stimulation.((The(increase(in(theta(frequency(from(dual(RPO(stimulation(relative(to(single(RPO(stimulation(is(contrary(to(what(was(expected.((The(result(suggests(that(during(electrical(stimulation(of(the(RPO,(some(current(may(be(leaking(to(structures(surrounding(the(RPO(like(the(MRN.((((When(the(right(RPO(was(stimulated(simultaneously(with(the(MRN,(the(frequency(at(which(theta(appeared(increased,(but(the(power(of(theta(declined.((This(result(challenges(previous(notions(that(increased(activation(of(the(MRN(suppresses(hippocampal(theta(oscillation(by(decreasing(theta(power(and(theta(frequency(and(calls(for(clarification(of(the(serotonergic(input(of(the(MRN(to(the(hippocampus.((((To(address(this(concern,(the(second(part(of(the(study(focused(on(selectively(activating(5VHT(neurons(of(the(MRN(through(optogenetic(technology.(In(the(remaining(group(of(10(rats,(each(animal(was(either(injected(with(lentivirus(expressing(a(GFP(protein(under(the(TPH(promoter(or(a(twoVcomponent(adenovirus(system(under(control(of(the(TPH(promoter(and(CRE(recombinase.((In(1(of(the(4(rats(injected(with(the(lentivirus,(5VHT(neurons(of(the(MRN(showed(GFP(expression.((None(of(the(6(rats(injected(with(the(twoVcomponent(adenovirus(system(showed(GFP(expression(in(5VHT(neurons(of(the(MRN.((Future(experiments(will(focus(on(tweaking(the(twoVcomponent(adenovirus(system(to(successfully(insert(the(channelrhodopsin(gene(in(5VHT(neurons(of(the(MRN(before(selectively(stimulating(these(neurons(with(light(and(recording(changes(in(hippocampal(theta(oscillations.((Optogenetics(will(reveal(a(clearer(mechanism(of(5VHT(influence(on(hippocampal(theta(oscillations.((( (

Investigating(the(use(of(Electroencephalography((EEG)(as(a(diagnostic(tool(in(the(predictor(of(ADHD(in(early(childhood(Research(Director:(Dr.(Margaret(Sheridan((AttentionVDeficit/Hyperactivity(Disorder((ADHD)(is(a(common(neurobehavioral(developmental(disorder(with(an(estimated(prevalence(of(approximately(3V5%(in(schoolVaged(children.((Children(with(ADHD(struggle(with(prominent(hyperactivity,(impulsivity,(and(inattention.(Often(these(impairments(in(both(cognitive(and(behavioral(functioning(result(in(limitations(in(multiple(domains.(Poor(academic(performance,(conduct(disorders,(lower(occupational(success(are(among(many(problems(associated(with(ADHD.(In(a(disorder,(which(has(lifelong(implications,(early(intervention(is(essential.(However,(currently,(ADHD(is(commonly(over(diagnosed,(especially(among(children(ages(3(to(4.(When(diagnosed(in(this(age(range,(only(approximately(50%(continue(to(meet(the(diagnostic(criteria(at(the(age(of(7.(Alternatively,(ADHD(diagnosis(at(age(7(and(older(maintains(diagnostic(stability.(In(the(current(study,(I(investigate(the(use(of(electroencephalography((EEG)(as(a(diagnostic(tool(for(ADHD(in(early(childhood.((I(examine(whether(established(EEG(data(abnormalities,(such(as(higher(theta/alpha(ratio(and(increases(in(theta(and(alpha(power,(found(in(ADHD(children(ages(7(years(old(and(older(can(be(found(in(children,(as(early(as(3(years(old,(who(have(high(ADHD(symptomology.((In(addition,(I(investigate(whether(differences(exist(between(high(and(low(ADHD(symptomology(in(children(ages(of(3(to(6(years(old.((Significant(differences(in(children(with(high(and(low(ADHD(symptomology(in(this(range,(will(suggest(the(potential(of(EEG(as(a(diagnostic(tool(in(ADHD(and(open(the(door(to(earlier,(more(accurate(ADHD(diagnosis.(( (

Investigation(of(Bilateral(Innervation(by(the(Facial(Nerve(on(the(Interscutularis(Muscle(Research(Director:(Dr.(Jeff(W.(Lichtman((One(part(of(the(motor(system(of(critical(importance(to(humans(is(the(motor(output(to(facial(muscles(via(cranial(nerves.(This(pathway(is(responsible(for(innervating(the(muscles(of(facial(expression(which(humans(depend(on(to(convey(emotions.(The(lower(motor(neurons(leave(the(brainstem,(where(the(facial(nerve’s(motor(nuclei(are(situated,(and(innervate(facial(muscles.(Conventional(thought(has(described(lower(motor(pathways(as(unilateral(tracts,(since(there(are(no(known(anatomical(connections(between(neurons(that(innervate(homologous(right(and(left(body(parts.(However,(previous(studies(have(established(that(this(assumption(can(bring(about(misleading(results,(because(for(reasons(unknown,(the(contralateral(side(is(sometimes(affected(by(perturbations(on(the(ipsilateral(side.(The(motivation(for(my(research(results(from(an(unanticipated(finding(that(detected(contralateral(effects(following(surgery(on(the(ipsilateral(side(of(the(interscutularis(muscle,(which(is(innervated(by(the(facial(nerve(that(attaches(to(the(base(of(the(ear(and(to(the(middle(of(the(skull.(The(present(data(showed(unexpected(denervations(of(some(neuromuscular(junctions((NMJs)(on(the(contralateral(interscutularis.(The(purpose(of(my(project(is(to(discover(the(cause(of(this(surprising(result.(My(hypothesis(is(that(the(muscles(are(connected(peripherally,(and(so(the(facial(nerve(would(bilaterally(innervate(the(intercutularis(muscles(that(are(situated(on(each(side(of(the(skull.(To(test(this(possibility,(I(have(retrogradely(labeled(the(motoneurons(of(the(interscutularis(muscles(with(fluorescent(Alexa(Fluor(conjugates(of(cholera(toxin(subunit(B.(My(results(are(still(pending.(( (

Maternal(separation(effects(in(GABAQdeficient(GAD65(KO(mice(Research(Director:(Dr.(Takao(Hensch((Early(life(stress,(such(as(maternal(separation,(in(rodents(results(in(lasting(changes(within(neural(circuits.(Maternal(separation(in(mice(results(in(increased(anxiety(and(fear(behavior(with(levels(differing(by(gender.(However,(variation(in(early(stress(effects(due(to(differing(genetics(has(been(little(studied.(This(study(explored(the(maternal(separation(effects(on(behavioral(and(genetic(changes(in(GAD65(V/V(mice(and(genetic(changes(in(Gclc(+/V(targeted(at(the(parvalbuminVpositive(interneurons(in(mice((PVVGclc(+/V).(Maternal(separation(was(performed(on(C57BL/6(+/+,(GAD65(V/V,(and(PVVGclc(+/V(mice(from(P2(through(P21(for(2(hours(per(day(in(parallel(with(nonVseparated(controls.(As(a(biomarker(of(stress,(qPCR(assays(of(telomere(length(on(ear(samples(collected(within(a(twoVweek(span(at(P75(and(P180(suggest(no(effects(of(maternal(separation(or(genotype(on(telomere(length(in(mice(at(P75,(but(reveal(that(maternally(separated(female(mice(had(longer(telomeres(than(their(controls,(whereas(male(mice(experienced(the(inverse(at(P180.(Prepulse(inhibition(of(acoustic(startle(response(revealed(that(maternally(separated(and(GAD65(V/V(male(mice(had(significantly(lower((p(<(0.05)(levels(of(prepulse(inhibition(as(compared(to(nonVseparated(and(C57BL/6(male(mice,(respectively.(These(results(suggest(a(gender(difference(in(maternally(separated(GAD65(V/V(mice(and(corroborate(evidence(that(GAD65(V/V(mice(experience(deficiencies(in(sensorimotor(gating.(Furthermore,(these(results(suggest(that(maternal(separation(do(not(affect(telomere(length(by(P75(and(that(early(life(stress(takes(a(greater(toll(on(GABA(deficient(mice.(( (

Neural(responses(to(facial(expressions(of(emotion:(A(comparison(study(in(three(developmental(populations(Research(Director:(Dr.(Charles(A.(Nelson((Past(research(suggests(that(both(biological(and(experiential(factors(contribute(to(the(ability(to(process(emotions(in(faces.((However,(this(ability(and(its(development(are(incompletely(understood.((I(examined(neural(and(behavioral(responses(to(facial(expressions(of(emotion(in(twelveVyearVolds(from(three(developmental(populations((typically(developing,(autism(spectrum,(and(institutionVreared),(with(two(main(objectives:((1)(to(characterize(responses(underlying(each(group’s(face(processing(and((2)(to(explore(how(biological(and(experiential(factors(might(shape(those(responses.((I(analyzed(eventVrelated(potentials((P100,(N170)(recorded(during(passive(viewing(of(neutral(faces(and(faces(with(lowVintensity(expressions(of(emotion((happy,(fearful,(angry)(and(results(from(a(behavioral(sorting(task(that(tested(emotion(recognition.((((My(analysis(is(in(its(early(stages,(so(I(was(unable(to(include(results(in(this(description,(but(these(data(should(provide(a(partial(characterization(of(each(group’s(face(processing.((Moreover,(by(comparing(these(populations,(I(hope(to(offer(insight(into(the(nature(and(development(of(this(ability,(with(particular(attention(to(the(roles(of(experience(and(biologically(inherited(circuitry.((((( (

NKCC1(Expression(on(Oligodendrocytes(During(Development(and(Following(Perinatal(HypoxiaQIschemia:(Conferring(Vulnerability(to(Periventricular(Leukomalacia?(Research(Director:(Dr.(Frances(E.(Jensen((Periventricular(leukomalacia((PVL)(is(the(major(type(of(hypoxicVischemic((HI)(brain(damage(observed(in(preterm(infants,(and(is(characterized(by(significant(white(matter(injury,(hypomyelination(and(damage(to(immature(oligodendrocytes((OLs).The(chloride(cotransporter(NKCC1(has(been(implicated(in(the(pathophysiology(of(epilepsy(and(adult(ischemia,(yet(little(is(known(about(its(role(in(PVL.(Thus,(we(aimed(to(1)(investigate(the(developmental(expression(of(NKCC1(in(cerebral(cortex(and(white(matter;(2)(characterize(the(spatiotemporal(changes(in(NKCC1(expression(following(HI;(and(3)(determine(whether(bumetanide,(an(NKCC1(blocker,(is(protective(in(HI.(NKCC1(protein(expression(was(assessed(using(immunohistochemistry(in(both(naïve(and(HI(LongVEvans(rats(and(PLPVEGFP(mice(from(postnatal(day((P)6V13.(In(separate(groups(of(mice(and(rats,(bumetanide((0.3(mg/kg)(administration(commenced(immediately(following(HI(and(was(given(q12(for(48h(until(euthanasia(at(P9(and(P13.(Semiquantitative(analyses(reveal(NKCC1(is(expressed(on(OLs((and(subplate(neurons(throughout(the(investigated(timecourse(with(a(peak(in(expression(at(P5VP7.(Following(HI(at(P6,(NKCC1(is(significantly(upregulated(on(OLs,(subplate(and(cortical(neurons(at(6h(and(24h((p<0.05).(This(increase(in(expression(coincides(with(region(specific(OL(cell(death(and(significant(increases(in(TUNELVpositive(OLs(up(to(72h(postVHI((p<0.05).(PostVHI(administration(of(bumetanide(reduced(the(number(of(FluoroJadeVpositive(degenerating(cells(in(the(cortical(mantle(and(underlying(white(matter(at(P13.(This(is(the(first(demonstration(that(NKCC1(is(expressed(on(OLs(during(normal(brain(development(and(is(upregulated(in(white(matter(and(cortex(acutely(following(HI.(It(is(also(the(first(evidence(for(a(protective(effect(of(bumetanide(in(an(animal(model(of(PVL.(Taken(together,(these(data(suggest(that(the(relative(overexpression(of(NKCC1(in(the(preterm(window(coincides(with(heightened(vulnerability(of(the(white(matter(to(HI(and(the(features(of(PVL.(( (

Novel(model(of(social(defeat:(The(divergent(effects(of(lithium,(valproic(acid,(and(resveratrol(in(Drosophila(melanogaster(Research(Director:(Dr.(Edward(A.(Kravitz((Approximately(one(in(six(Americans(will(suffer(from(major(depressive(disorder,(which(is(predicted(to(become(a(leading(cause(of(disability(worldwide(by(2020.(Unfortunately,(all(of(the(medications(in(widespread(use(for(depression(are(based(on(a(few(molecular(mechanisms(that(were(identified(almost(fifty(years(ago.(((Animal(models(can(be(used(to(discover(novel(treatment(mechanisms.((We(are(using(a(relatively(new(behavioral(paradigm(in(the(fruit(fly,(Drosophila(melanogaster.(((Of(particular(relevance(to(psychiatric(research(is(the(finding(that(the(experience(of(losing(a(fight(affects(the(defeated(fly(in(a(profound(and(longVlasting(manner;(after(a(single(defeat,(the(loser(will(lose(subsequent(fights(approximately(90%(of(the(time.(I(treated(flies(with(different(pharmacological(compounds(and(determined(their(effect(on(losing(or(winning.((I(found(that(different(pharmacological(interventions(relevant(for(human(mood(disorder(patients(affected(Drosophila(social(defeat(behavior(in(divergent(ways.((5VHydroxytryptophan,(the(chemical(precursor(to(serotonin,(increased(the(resilience(of(losers(to(future(losses.((Lithium(also(increased(resilience(of(losing(flies(such(that(losers(lost(only(46%(of(subsequent(fights.((Valproic(acid(treatment(seemed(to(stabilize(the(winnerVloser(status(between(fights(such(that(losers(lost(100%(of(second(fights(while(winners(won(75%(of(second(fights.((Resveratrol(increased(resilience(in(losers(allowing(them(to(lose(only(40%(of(second(fights.((Drosophila(social(defeat(behavior(was(found(to(be(responsive(to(relevant(pharmacological(treatments(used(in(human(patients(and(may(lay(the(foundations(for(the(discovery(of(novel(treatments(for(depression.((((( (

Optical(control(of(behavior(in(the(trained(mouse:(Neuronal(processing(examined(through(psychometric(slope(and(reaction(time(Research(Director:(Dr.(John(Maunsell((The(quest(to(understand(how(neural(circuits(control(behavior(remains(a(fundamental(aim(in(systems(neuroscience.((A(major(complicating(factor(for(studying(circuits(is(the(issue(of(noise,(which(derives(from(numerous(sources,(is(ubiquitous(through(the(processing(pathway,(and(correlates(across(neurons.(Research(into(neural(circuits(and(noise(has(largely(been(confined(to(the(theoretical(domain(due(to(technological(limitations(precluding(the(precise(activation(of(wellVdefined(neural(populations.(In(this(study,(we(employed(novel(optogenetic(techniques(on(the(behaving(mouse(in(order(to(overcome(this(limitation.(We(have(shown(that(mice(can(be(trained(to(respond(reliably(near(threshold(levels(to(optical(stimulation.(We(have(compared(psychophysical(measurements(of(noise(and(threshold(for(animals(responding(to(visual(and(photo(stimuli.([Results(and(conclusions(in(progress.(We(hope(that(this(study(will(help(elucidate(the(mechanisms(of(preVcortical(noise.(We(also(seek(to(demonstrate(the(potential(of(optical(stimulation(for(the(study(of(neural(coding,(and(to(make(observations(about(methods(for(collecting(psychophysical(data.(This(will(be(done(in(the(near(future.](( (

Quantitative(behavioral(analysis(of(central(brain(circuits(for(light(avoidance(in(Drosophila(larvae(Research(Director:(Dr.(Aravi(Samuel((Most(animals(have(developed(mechanisms(to(extract(and(respond(to(directional(signals(from(the(environment.(In(complex(animals,(the(neural(connections(between(sensory(input(and(motor(output(are(beyond(our(current(understanding.(However,(we(can(gain(insight(into(principles(of(the(circuitry(by(studying(a(genetically(tractable(organism(such(as(the(Drosophila(larva.(The(larva(also(exhibits(strong(navigational(behaviors(that(facilitate(the(study(of(sensorimotor(transformations.(In(studying(navigation(away(from(light,(one(important(target(is(the(group(of(clock(neurons(responsible(for(setting(circadian(rhythms;(these(neurons(have(internal(molecular(cycles(that(can(be(entrained(by(lightVdark(cycles.(The(main(goal(of(this(project(was(to(investigate(the(role(of(timelessVexpressing(clock(neurons(in(light(avoidance(behavior(of(Drosophila(larvae.(We(created(mutant(timeless(UAS)VGal4(x(UASVshibirets(larvae(whose(timelessVexpressing(neurons(were(conditionally(silenced(above(the(restrictive(temperature;(we(then(tracked(their(movements(in(response(to(a(directional(light(source.(Silencing(the(timelessVexpressing(neurons(did(not(affect(overall(navigation(or(any(parameters(we(measured.(Given(the(prior(conflicting(evidence(on(the(role(of(clock(neurons(in(larval(phototaxis,(this(result(suggests(that(phenotypic(changes(in(light(avoidance(may(be(too(subtle(to(be(detected(by(some(assays,(and(suggests(that(the(developmental(effects(of(disrupting(the(clock(circuit(should(be(examined(more(closely.(( (

Searching(for(molecular(markers(of(feedback(neurons(in(mouse(visual(cortex(Research(Director:(Dr.(Richard(T.(Born((In(the(mammalian(brain,(the(visual(system(is(organized(in(a(hierarchy(of(cortical(areas.((The(connections(between(regions(in(this(hierarchy(are(thought(to(play(an(important(role(in(visual(perception.((Feedforward(neurons(project(from(lower(to(higher(visual(areas(and(are(thought(to(integrate(basic(stimulus(features,(while(the(function(of(feedback(projections,(which(descend(from(higher(to(lower(areas,(remains(poorly(understood.(A(recent(study(has(shown(that(feedforward(and(feedback(neurons(comprise(largely(independent(populations(in(the(upper(layers((2/3)(of(the(mouse(visual(cortex,(but(it(is(unknown(whether(gene(expression(can(differentiate(feedback(from(feedforward(neurons.((To(search(for(molecular(markers(of(feedback(neurons,(we(used(a(candidate(gene(approach.((We(injected(a(retrograde(tracer(into(primary(visual(cortex((V1)(of(adult(mice(to(label(feedback(neurons(in(lateromedial(secondary(visual(cortex((LM)(as(well(as(feedforward(neurons(in(the(lateral(geniculate(nucleus((LGN).((For(two(candidate(genes(expressed(primarily(in(cortical(layer(2/3,(Cux2(and(Pvrl3,(we(performed(in(situ(hybridization(on(tissue(sections(containing(labeled(feedback(and(feedforward(neurons(and(looked(for(coVlocalization(of(gene(expression(and(tracerVlabeling(in(LM(and(LGN.(((Preliminary(results(show(that(86%(of(LM(feedback(cells(express(Cux2,(in(contrast(to(only(53%(of(LGN(feedforward(cells,(and(similar(analyses(are(being(performed(for(Pvrl3.((Our(results(show(that(the(candidate(gene(approach(can(reveal(genes(that(may(be(expressed(preferentially(in(feedback(neurons.((In(addition,(our(approach(would(allow(the(validation(of(genes(identified(by(a(comparative(microarray(screen(of(feedback(and(feedforward(neurons,(and(thus(is(an(important(step(in(the(identification(of(molecular(markers(for(these(populations.(( (

Significance(of(the(putative(dsRNA(transporter(SidT2(in(mammalian(behavior(Research(Director:(Dr.(Craig(P.(Hunter((Systemic(RNAi(in(C.(elegans(relies(on(the(transmembrane(protein(SIDV1,(a(dsRNA(transporter.(The(gene(for(this(protein(is(highly(conserved(in(animals.(Although(systemic(RNAi(has(not(been(observed(in(vertebrates,(all(known(vertebrates(share(sidV1(homologs(called(SidT1(and(SidT2.(The(functions(and(purposes(of(these(genes(have(not(been(fully(characterized.(This(study(focused(on(SidT2,(which(is(strongly(expressed(in(the(brain(among(other(tissues.(The(aim(of(the(study(was(to(clarify(the(role(of(SidT2(in(the(mammalian(brain.((The(question(was(addressed(in(a(SidT2(knockdown(mouse(model.(First,(SidT2(knockdowns(were(compared(to(wildVtype(controls(on(a(battery(of(standard(behavioral(tests,(covering(the(areas(of(sensory(acuity;(motor(activity(and(function;(learning(and(memory;(prepulse(inhibition((a(correlate(of(psychosis);(fear(and(anxiety;(and(depression.(Knockdowns(and(controls(performed(similarly(on(most(tests,(but(there(were(notable(differences(on(some(anxiety(and(depression(assays.(On(two(of(three(types(of(depression(assay,(the(knockdowns(showed(increased(depressionVlike(behavior.(The(third(result(was(ambiguous.(Knockdowns(showed(decreased(anxietyVlike(behavior(on(freezing(and(marble(burying(tests,(but(increased(anxietyVlike(behavior(on(three(other(anxiety(assays,(specifically(in(the(form(of(decreased(exploratory(behavior.(Other(than(exploratory(behavior,(the(results(were(consistent(with(the(reported(behavioral(effects(of(SSRI(antidepressants.((A(BrdU(assay(ruled(out(a(difference(in(adult(hippocampal(neurogenesis.(Hippocampal(mass(and(morphology(were(also(similar(as(far(as(could(be(observed.(((Regarding(the(antidepressant(and(anxiolytic(effects(of(SidT2(knockdown,(it(is(speculated(here(that(SidT2(has(a(role(in(serotonin(regulation.(The(decrease(in(exploratory(behavior(is(not(yet(explained,(but(may(be(due(to(undetected(differences(in(sensory(acuity(or(processing.((( (

Sleep(and(ecological(memory(Research(Director:(Dr.(Robert(Stickgold((The(consolidation(of(memories(that(occurs(during(sleep(has(been(investigated(using(word(pairs(and(other(laboratory(produced(visual(and(audio(stimuli.(It(has(been(found(that(many(memories,(both(declarative(and(nonVdeclarative(are(remembered(better(after(sleep,(suggesting(that(memories(for(the(stimuli(tested(are(consolidated(more(during(sleep(then(they(are(during(wake.((However,(it(is(not(memories(for(laboratoryVproduced(stimuli(that(help(shape(the(decisions(that(we(make(in(every(day(life.(It(is(autobiographical(memories(of(real(life(events(that(we(use(to(make(decisions(in(the(future.(This(study(looks(at(how(a(nap(affects(memory(for(autobiographical(events.((During(the(morning(the(participants(wearing(a(sense(came((a(small(camera(worn(around(the(neck)(travelled(to(the(Museum(of(Science,(participated(in(32(different(activities(within(the(museum(and(then(travelled(to(the(lab.(While(at(the(lab(they(either(napped((90(minutes(with(high(density(EEG)(or(participated(in(quiet(wake(and(then(underwent(an(hourVlong(test,(designed(to(assess(their(memory(of(both(the(activities(they(participated(in(at(the(museum(as(well(as(the(trips(to(and(from(the(museum.((At(this(point(in(analyses(no(difference(in(performance(on(the(memory(test(has(been(seen(between(the(sleep(and(wake(group.(This(is(very(interesting(and(suggests(that(perhaps(there(is(a(difference(between(the(memories(produced(in(a(laboratory(environment(and(those(that(occur(naturally(during(dayVtoVday(life.(Analyses(of(sleep(stages(is(in(progress((( (

Sleep(and(Motor(Memory(Research(Director:(Dr.(Robert(Stickgold((There(is(extensive(research(regarding(the(role(of(sleep(in(memory(consolidation.(In(particular,(procedural(memory,(or(motor(memory,(has(been(found(to(be(sleepVdependent.(In(these(experiments(we(studied(motor(memory(using(an(explicit(motorVsequence(learning(paradigm,(the(Motor(Sequence(Task((MST).(It(has(been(reported(that(performance(on(the(MST(remain(stable(across(periods(of(wake(and(significantly(improves(across(equivalent(periods(of(sleep.(However,(in(some(studies,(performance(on(the(MST(was(found(to(improve(significantly(after(the(first(5V30(minutes(postVtraining,(without(any(sleep;(this(observation(has(been(characterized(as(a(“boost(effect.”(The(observed(boost(was(shortVlived(and(was(followed(by(significant(decreases(in(performance(across(wakefulness,(with(sleep(restoring(and(maintaining(subsequent(performance(to(postrest(level.((Here,(we(further(investigated(both(the(role(of(sleep(in(memory(consolidation(and(the(boost(effect(using(two(studies.(In(Study(1,(participants((n=##)(trained(on(the(MST(were(retested(after(breaks(lasting(5,(30,(90,(and(240(minutes.(In(Study(2,(subjects(were(assigned(to(either(the(wake((n=12)(or(sleep((n=12)(condition(and(were(tested(90(minutes(after(training.((Interestingly,(participant's(performance(during(retest(on(the(MST(significantly(improved,(regardless(of(the(duration(of(the(break.(((( (

Study(of(ERP(response(in(word(recognition(by(toddlers(at(risk(for(Autism(Spectrum(Disorders(Research(Director:(Dr.(Charles(A.(Nelson((Principal(objectives:(To(elucidate(the(nature(of(language(impairments(commonly(found(in(autism(spectrum(disorders((ASD),(I(examined(the(neural(correlates(of(word(processing(in(this(study.(This(project(also(shed(further(light(on(the(endophenotype(associated(with(ASD.(Infants(were(studied(at(24Vmonths(of(age(to(examine(whether(neural(atypicalities(or(deficits(in(processing(individual(words(correlate(with(language(ability(or(symptoms(of(ASD.(Specifically,(two(groups(of(children(were(included:(1)(infants(who(are(at(high(risk(for(developing(ASD(by(virtue(of(having(an(older(sibling(with(the(disorder((HRA)(and(2)(lowVrisk(control(infants(with(only(typicallyVdeveloping(siblings((LRC).(Methods:((Electrophysiological(recordings(were(collected(from(HRA(and(LRC(subjects(in(response(to(words(that(are(either(known(or(unknown(to(most(infants(at(that(age.(I(analyzed(the(negative(eventVrelated(potential((ERP)(component(N300(and(the(positive(P100(to(study(this(response(across(study(groups.(Behavioral(and(language(assessments,(in(addition(to(ASD(diagnostic(measures,(were(obtained(from(all(subjects(to(categorize(their(communicative(development.((Results:(For(both(groups,(word(type((known(versus(unknown)(affected(the(amplitude(of(both(components(studied.((The(lateralization(of(the(N300(was(also(influenced(by(the(child’s(study(group:(a(more(negative(response(was(found(in(the(right(hemisphere(for(group(mean(of(HRA,(and(in(the(left(hemisphere(for(LRC.((Conclusions:((These(findings(suggest(a(potential(reversal(of(hemispheres(for(word(processing(among(participants(at(high(risk(for(ASD,(replicating(results(seen(in(older(subjects(with(ASD.( (

Studying(the(role(of(the(striatum(in(a(DARPPQ32(Tsc1(mouse(model(of(autism(Research(Director:(Dr.(Mustafa(Sahin((The(pathological(mechanism(underlying(the(high(prevalence(of(autism(spectrum(disorders(in(patients(with(Tuberous(Sclerosis(Complex(is(still(largely(unknown.(When(studies(suggested(that(the(high(coVmorbidity(of(these(two(disorders(might(to(be(due(to(dysfunctional(neural(networks(in(multiple(anatomic(areas,(the(cerebral(cortex(and(cerebellum(became(the(predominant(areas(of(interest(due(to(their(historical(association(with(autism(spectrum(disorders.(Consequently,(less(is(known(about(the(potential(involvement(of(other(subcortical(structures,(specifically(the(striatum,(which(have(only(recently(been(linked(to(autism.(This(study(examined(the(role(of(the(striatum(in(the(appearance(of(autistic(behaviors(in(a(mouse(model(of(Tuberous(Sclerosis(Complex,(in(which(a(dopamineVreleasing(protein((DARP)(promoter(was(used(to(localize(the(heterozygote(Tsc1(knockout(to(the(striatum.(Behavioral(tests(were(conducted(to(detect(abnormalities(in(any(of(the(three(behavioral(diagnostic(criteria(of(autism(spectrum(disorders,(which(include(communication(deficits,(impairments(in(social(interaction,(and(ritualistic(or(repetitive(behaviors.(Differences(in(ultrasonic(vocalizations(emitted(by(DARPP(Tsc1(mutant(pups(and(control(pups(when(separated(from(their(mothers(suggest(a(potential(communication(deficit.(However,(no(significant(difference(was(found(in(tests(of(social(interaction(with(other(mice(and(objects,(resistance(to(change(using(the(T(water(maze,(grooming(behaviors,(or(anxiety(using(the(elevated(plus(maze(and(open(field(tests.((The(results(of(these(studies(indicated(that(the(control(mice(were(not(as(social(and(did(not(learn(the(water(maze(task(as(expected.(These(atypical(control(results(make(it(difficult(to(accurately(assess(any(differences(in(mutant(behavior.(( (

Transdifferentiation(of(Nociceptive(Neurons(from(Mouse(Embryonic(Fibroblasts(Research(Director:(Dr.(Clifford(Woolf((Once(pain(ceases(playing(a(protective(role(and(instead(becomes(persistent(and(debilitating,(pain(becomes(a(disease.((Chronic(pain(poses(a(significant(health(problem,(and(the(mechanisms(that(give(rise(to(it(are(still(poorly(understood.((As(a(result,(patients(receive(insufficient(relief(from(current(pain(therapies,(and(are(at(risk(of(severe(or(often(dangerous(side(effects.((Motivated(by(the(need(for(more(accurate(and(reliable(pain(models,(we(aim(to(shift(pain(research(to(human(models(of(human(pain(using(recent(stem(cellVrelated(techniques.((The(goal(of(the(project(was(to(establish(a(protocol(for(reprogramming(mouse(embryonic(fibroblasts((MEFs)(into(painVsensitive(neurons((nociceptors).((First,(we(established(a(nociceptorVspecific(reporter(by(making(Nav1.8::Tomato(MEFs.((We(then(identified(16(transcription(factors(crucial(to(nociceptor(development(and(survival,(inserted(those(factors(into(retroviruses,(and(finally(infected(populations(of(Nav1.8::Tomato(MEFs(with(different(combinations(of(the(viruses.((After(immunostaining(the(reprogrammed(cells(for(nociceptor(markers(and(performing(electrophysiology(and(calcium(imaging(on(the(TomatoVpositive(cells,(we(refined(the(list(of(16(factors(to(a(smaller(subset(sufficient(for(inducing(the(salient(characteristics(of(nociceptors.((The(next(steps(will(be(to(alter(the(transdifferentiation(approach(to(derive(nociceptors(from(mouse(as(well(as(human(induced(pluripotent(stem(cells,(and(to(accomplish(the(same(transdifferentiation(of(human(adult(fibroblasts(specifically(from(patients(with(gain(of(function(mutations(in(Nav1.7(for(further(pain(research.((The(versatility(of(our(work(will(bring(about(important(advances(in(human(diseaseVmodeling,(cell(therapies,(and(drugVtarget(screens.(( (

Using(Brain(Electrical(Source(Analysis((BESA)(to(Localize(Areas(of(Development(of(Face(Processing(in(Infants(at(Risk(for(Developing(Autism(Spectrum(Disorder((ASD)(Research(Director:(Dr.(Charles(A.(Nelson((Studying(the(development(of(face(processing(in(humans(provides(insight(into(both(visual(and(social(development.(Furthermore,(examining(how(infants,(who(are(at(risk(for(developing(Autism(Spectrum(Disorder((ASD),(process(faces(provides(further(information(about(the(social(brain.(The(development(of(their(social(processing(may(already(begin(to(differ(at(6(months(from(a(typically(developing(individual’s.(In(this(study,(we(recorded(the(brain(activity(of(6(month(old(infants(using(electroencephalogram((EEG)(during(a(passive(viewing(paradigm(of(familiar(and(unfamiliar(faces.((When(studying(human(brain(development,(generally(only(noninvasive(techniques(such(as(EEG(are(used(on(healthy(infants,(limiting(the(spatial(resolution(of(measured(brain(activity.(EEG(measures(surface(potentials,(which(result(from(large(numbers(of(neurons(firing(simultaneously(within(the(brain.(These(areas(of(brain(activity(can(be(modeled(as(current(dipoles.(These(dipoles(are(a(separation(of(charge(being(rectified(by(current(flowing(throughout(the(brain.(Thus,(using(a(technique(called(source(analysis(scalp(potentials(can(be(used(to(inversely(solve(for(an(origin(of(activity.(After(performing(source(analysis(with(BESA(software(on(the(segmented(EEG(data,(we(localized(activity(to(the(frontal(lobe,(anterior(cingulate,(cingulate(gyrus,(fusiform(gyrus,(occipital(lobe,(and(areas(of(the(cerebellum(near(the(occipital(regions.([Further(discussion]( (

Visual(Function(in(the(NeuroliginQ3(R451C(Autism(Mouse(Model(Research(Director:(Dr.(Michela(Fagiolini((While(autism(spectrum(disorders((ASD)(are(characterized(by(repetitive(behaviors(and(dramatic(deficits(in(socialization(and(communication,(some(autistic(individuals(also(exhibit(abnormal(sensory(function.(The(development(of(model(systems(is(needed(to(study(the(neural(correlates(of(such(sensory(abnormalities.(In(visually(evoked(potential((VEP)(recording(experiments,(the(anesthetized(neuroliginV3(R451C(knockVin(mouse(model(of(autism(exhibits(higher(visual(acuity(levels(than(littermate(controls,(making(it(a(potentially(salient(model(for(studying(enhanced(visual(function(in(ASD.(However,(without(understanding(the(behavioral(phenotype(of(the(animal,(it(is(difficult(make(claims(about(the(relevance(of(these(findings(in(the(anesthetized(visual(cortex.(We(conducted(two(behavioral(assays,(the(Visual(Water(Task(and(Optomotor(Task,(to(assess(the(visual(acuity(of(NL3(R451C(knockVin(mice.(The(Visual(Water(Task(is(a(twoVchoice(forcedValternative(test(in(which(mice(are(released(in(a(water(tank(and(trained(to(swim(toward(a(grating(stimulus(of(varying(barVwidth.(The(Optomotor(Task(measures(subcortical(visual(acuity(by(detecting(an(innate(headVtracking(response(to(a(drifting(grating(pattern.(The(NL3(R451C(knockVin(mice(unexpectedly(had(lower(visual(acuity(than(wildtype(controls(in(the(Visual(Water(Task,(but(they(also(demonstrated(a(learning(deficiency(during(the(training(phase(of(the(experiment.(In(contrast,(the(knockVin(mice(exhibited(a(trend(of(higher(visual(acuity(in(the(optomotor(task.(While(no(conclusive(results(were(found,(it(is(possible(that(increased(anxiety(in(the(NL3(R451C(mutant(masked(any(detectable(enhanced(visual(acuity(in(the(Visual(Water(Task.(( (

Weight(of(Reward:(The(Neurobiology(of(Deception(Research(Director:(Dr.(Joshua(Greene((It(is(often(assumed(that(the(choice(to(remain(morally(responsible(depends(entirely(on(given(circumstances(and(one’s(personal(convictions(based(on(experience,(not(cellular(mechanisms.(This(study(sought(to(explore(correlations(between(the(relative(size(of(certain(regions(of(the(human(brain(and(the(frequency(of(dishonest(behavior(using(voxelVbased(morphometry((VBM).(We(asked(28(human(subjects(to(play(a(coinVflip(game(with(a(computer(in(an(MRI(scanner(where(existed(a(monetary(incentive(to(lie,(and(were(able(to(look(at(brain(structure(and(behavior(simultaneously.(These(subjects(were(told(to(predict(the(outcome(of(a(coinVflip(and(then(asked(to(report(if(their(prediction(was(correct.(A(positive(answer(yielded(a(monetary(reward(the(size(of(which(was(displayed(before(each(flip.(We(used(Statistical(Parametric(Mapping(software(to(analyze(the(scans,(and(found(that(there(are(multiple(regions(that(play(a(role(in(the(complicated(decisionVmaking(process(of(telling(lies.(Specifically,(based(on(significant(associations(between(frequency(of(dishonest(behavior(and(gray(matter(volume((GMV),(we(concluded(that(the(size(of(the(ventral(striatum(may(contribute(to(one’s(propensity(to(be(dishonest.(This(suggests(that(the(size(of(the(region(that(governs(reward(processing(is(a(significant(indicator(of(the(presence(of(a(very(complex(behavior.(Thus,(it(is(very(possible(that(genetics(and(other(factors(governing(the(structure(of(the(brain(could(conceivably(influence(behavior(in(the(same(ways(that(context(or(past(experiences(can.(( (

Why(Plasticity(Matters:(The(Effects(of(Music(Exposure(during(a(“Critical(Period”(of(Anxiety(Circuit(Development(Research(Director:(Dr.(Takao(Hensch((Anxiety(disorders(are(marked(by(elevated(baseline(or(“state”(anxiety(outside(of(normal(anxietyVprovoking(situations.(Previous(studies(have(traced(a(possible(root(of(these(disorders(to(early(neural(development(and(environmental(exposure.(Interestingly,(music(has(been(tied(to(both(neural(plasticity(and(treatment(of(anxiety,(but(these(aspects(have(only(been(explored(separately.(This(thesis(thus(relates(the(concept(of(anxiety(to(developmental(plasticity(and(music(exposure.(Behavioral(experiments(were(performed(in(C57BL6(mice(exposed(to(music((or(not)(during(fixed(windows(of(development:(postnatal(day(P5V14,(P15V24,(P25V34,(P35V44,(and(adulthood((>P60).(Upon(reaching(P60,(mice(from(each(group(were(run(on(a(novel(twoVchoice(preference(task(that(doubled(as(an(open(field(test(for(anxiety.(Only(those(mice(exposed(during(P15V24(exhibited(a(striking(preference(switch(in(favor(of(music(unlike(the(innate(bias(for(silence(in(control(animals.(Concurrently,(these(mice(showed(the(lowest(levels(of(anxiety((as(measured(by(open(field(center(crossings).((Further(experiments(explored(the(possibility(of(extended(plasticity(and(anxiolysis(by(music(in(adult(animals.(Mice(lacking(the(nicotinic(acetylcholine(receptor(‘brake’(Lynx1,(which(limits(plasticity(in(the(sensory(cortices(of(adult(mice,(were(exposed(to(music(as(adults((>P60)(and(are(currently(being(analyzed.(Overall,(these(results(indicate(a(potential(interaction(between(neural(circuits(underlying(anxiety(and(music(preference(during(development,(as(well(as(a(potential(synergistic(effect(of(music(combined(with(extended(neural(plasticity(in(adulthood(that(leads(to(reduced(anxiety.( (