suspiggycase

InhibitionHasLittleEffectonResponseLatenciesintheInferiorColliculusZOLTANM.
FUZESSERY,1JEFFREYJ.
WENSTRUP,2JIMC.
HALL,3ANDSCOTTLEROY21DepartmentofZoologyandPhysiology,UniversityofWyoming,Laramie,WY82071,USA2DepartmentofNeurobiologyandPharmacology,NortheasternOhioUniversitiesCollegeofMedicine,Rootstown,OH44272,USA3DepartmentofBiochemistryandCellularandMolecularBiology,UniversityofTennessee,Knoxville,TN37996,USAReceived:27November2001;Accepted:3June2002;Onlinepublication:19August2002ABSTRACTTheinferiorcolliculiofallmammalsarecharacter-izedbyawiderangeofrst-spikeresponselatenciesthatcangreatlyexceedtheminimumtimerequiredforthetransmissionofinputthroughthelowerbrainstem.
Themechanismsthataccountforlongresponselatenciesofupto50msareunclear,butonehypothesisisthatanearlyinhibitionplaysaroleinshapinglatency.
Totestthishypothesis,responsela-tenciesweremeasuredintheinferiorcolliculiofthepallidandmustachedbatsbeforeandduringtheblockadeofGABAaandglycinereceptors.
Theeffectofblockinginhibitiononresponselatencywascom-paredunderstimulusconditionsthatproducedtheshortestlatencyinthepredrugcondition.
Multibarrel''piggyback''electrodeswereusedtoiontophoreti-callyapplybicucullineandstrychninesequentiallywhilerecordingfromsingleneurons.
Predruglaten-ciesrangedfrom9to26msinthepallidbatandfrom4to17msinthemustachedbat.
Despitelargein-creasesinresponsemagnitudeandresponsedurationfollowingdisinhibition,theblockadeofinhibitoryreceptorshadmodesteffectsonresponselatency.
Inthepallidbat,blockingGABAreceptorsproducedlatencychangesthatrangedfrom)3.
8to+0.
2ms,whileblockingglycinereceptorsproducedchangesfrom)0.
1to+1.
7ms.
Similarly,inthemustachedbat,blockingGABAreceptorscausedchangesrangingfrom)10.
3to+1.
4ms;blockingglycinereceptorsinthemustachedbatcausedchangesfrom)3.
6to+1.
0ms.
Thelargechangeof)10.
3mswasanexception.
Inbothspecies,themajorityofneuronsshowedchangesof40kHz)arelocatedmoremediallyanddonotextendtothelateralwalloftheIC(Fig.
2).
NeuronsinthelateralIChaveresponselatenciesasshortas5ms,theshortestrecordedintheIC(Fig.
2).
Basedontheaboveestimateofthearrivaltimesofafferentinput,theseresponselatenciesprobablyrepresenttheshortestpossibleresponsetimesinthepallidbatICC.
Incontrast,fewneuronstunedtothesamelow-frequencyrangeinthemedialIChadre-sponselatenciesof50kHz(Fig.
4).
Onlyonehadalowerbestfrequencyof25.
4kHz.
Allneuronswerecombi-nation-sensitive,asdescribedinPortforsandWenst-rup(1999).
Theirpredrugresponselatenciesrangedfrom4.
0to17.
2ms(Fig.
4),arangewhichissimilartothosereportedinpreviousstudiesofneuronstunedtothehigherharmonicsoftheecholocationpulse(HattoriandSuga1997;PortforsandWenstrup2001),butwhichdoesnotincludethemuchlongerlatencies(upto45ms)reportedinthehypertrophied60kHzregionofthemustachedbatinferiorcollicu-lus(ParkandPollak1993).
Inall38neuronstestedinthepallidbat,andin21ofthe52neuronstestedinthemustachedbat,re-sponselatenciesbeforeandduringdisinhibitionweremeasuredovertheirdynamicintensityrangebecauseintensitylevelcanhavealargeeffectonlatency(e.
g.
,IrvineandGago1990;Klugetal.
2000),withlatencytypicallydecreasingwithincreasingintensitylevel(Figs.
5and6,rightcolumns).
ThechangeinlatencyascribedtodisinhibitionwasmeasuredattheintensitylevelthatproducedtheshortestlatencyinFIG.
3.
Left:ThreeelectrodepenetrationsthroughthepallidbatIC,varyinginlateromediallocation.
Right:Thelatenciesandbestfrequenciesofneuronsrecordedinthethreepenetrationsshowingthatlatencyvariedasafunctionofbestfrequencyandlocation.
FIG.
2.
Left:TransversesectionofthepallidbatICshowingisofrequencycontoursandfunctionallydenedmedialandlateralregions(verticaldashedline).
Right:ThedistributionofresponselatenciesinthepallidbatICasafunctionofbestfrequencyandlocationinthemedial(lledcircles)andlateral(opensquares)regionsoftheIC.
NeuronsinthelateralICaretunedto0.
5mswereobservedonlywhenglycinereceptorswereblocked.
Similarchangesinlatencywereobservedacrossbestfrequencies(Fig.
7C)andalsoacrosstherangeofpredruglatencies(Fig.
7A).
TheaveragelatencychangewhenblockingGABAareceptorswas)0.
7ms(range=)3.
8to+0.
2ms,SD=1.
0ms).
Theaveragechangewhenblockingglycinereceptorswas)0.
1ms(range=)1.
3to+1.
7ms,SD=0.
8ms).
Inthemustachedbat,changesinresponselatencyrangedfromadecreaseof10.
3mstoanincreaseof1.
4ms,but,asinthepallidbat,themajorityshowedchangesof0.
65).
RepresentativechangesintemporalresponsepropertiesareshowninFigure8.
Inthepallidbat(Fig.
8,leftcolumn),theneuroninFigure8A,Bshowedanaverage0.
8msdecreaseinlatencyinre-sponsetobicuculline.
Inthepredrugcondition,theneuronredonespike.
Duringbicucullineapplica-tion,itredtwospikesinthisintialburst,therstspikeoccurring0.
5–12msearlierthaninthepredrugcondition,followedbyathirdspikeofirregulartim-FIG.
4.
ThedistributionofnormalresponselatenciesofneuronsintheICsofthepallidbat(left)andmustachedbat(right)priortoblockadeoftheirinhibitoryinputs.
Forthemustachedbat,neuronsinwhichresponselatenciesweretestedoverthedynamicintensityrangeoftheneuronareindicatedbyopencircles.
Thosetestedat10dBabovethresholdareindicatedbylledcircles.
FUZESSERYETAL.
:InhibitionandResponseLatency65ing.
Bicucullineappearedtoreleasethisneuronfrominhibitionthatoccurredbothbeforeandafterthenormalexcitation.
DisinhibitionbybicucullinehadsimilarbutgreatereffectsontheneuroninFigure8C,D.
Itsometimesredarstspikeapproximately2msearlierthaninthepredrugcondition,butbecausethisearlyresponsewasinconsistent,itsaveragela-tencywaslongerandtherewasonlya0.
8msdiffer-enceinmeanlatenciesunderthetwoconditions.
Thetimingofthesecondpeakofrst-spiketimingduringbicucullineapplicationissimilartothatoftherstpeakinthepredrugcondition.
ThisresultsuggeststhatbicucullineblockedanearlyGABAergicinhi-bitionthatretardedtheresponselatencyofthisneuron.
Asinthepreviousneuron(Fig.
8A,B),bic-ucullinealsoremovedalateinhibitionandgreatlyincreasedtheresponseduration.
TheneuroninFigure8E–Gwassequentiallyex-posedtobicucullineandstrychnine.
Bicucullinein-creasedthedurationandmagnitudeofitsresponseanddecreasedresponselatencyanaverageof1.
0ms(Fig.
8G).
Incontrast,strychnineincreaseditslatencybyanaverageof1.
7ms(Fig.
8F).
AswastypicallytheFIG.
5.
FourneuronsfromthepallidbatICshowingtheeffectofblockingGABAergicinputwithbicuculline(Bic)orglycinergicinputwithstrychnine(Strych)relativetothepredrug(Pre)condition.
Leftcolumnshowstheeffectofdisinhibitiononintensity–ratefunctions.
Rightcolumnshowstheeffectofresponselatencyasafunctionofintensitylevel.
Thearrowsintherightcolumnindicatetheintensitylevelatwhichchangesinresponselatencyweremeasured.
Thesamesymbolsareusedinthepairsofguresintheleftandrightcolumnstoindicatedrugandpredrugconditions.
66FUZESSERYETAL.
:InhibitionandResponseLatencycase,bicucullineincreasedresponsemagnitudemorethanstrychnine.
Similarchangesinpoststimulustimehistogramswereseeninthemustachedbat(Fig.
8,rightcol-umn).
Figure8H,Ishowsthelargestlatencychangeobservedafterapplicationofanantagonistinthisstudy,10.
3ms.
Incontroltests,theunitrespondedonaveragewithonespiketothebestfrequencystimulus.
Therstspikeoccurredaslittleas11msafterstim-ulusonset,but,becauseofthehighvariability(SD=6.
0ms),themedianlatencywas17.
5ms.
Withbicuculline,theresponserateincreasedbyafactorof5.
Theearliestlatenciesdecreasedto7msandthedistributionoflatencieswasmuchtighter(SD=1.
1ms,medianlatency=7.
2ms).
Thus,bicucullinere-vealedtwolargeeffectsofGABAainhibitiononla-tency:adecreaseintherst-spiketimingandanincreaseintheconsistencyoftherstspike.
Suchlargecombinedeffectswerenotseeninotherunits.
Figure8J,Kshowsaverysmalleffectofbicucullineonlatencydespiteamajoreffectonresponsemagni-tude.
Theunit(alsoshowninFig.
6G,H)respondedweaklyinthecontrolcondition,butthelatencyofresponsevariedlittle(SD=0.
8ms,medianlaten-FIG.
6.
FourneuronsfromthemustachedbatIC.
ThesameconventionasinFig.
4wasusedtoshowtheeffectsofbicucullineand/orstrychnineonintensity–ratefunctionsandintensity–latencyfunctions.
FUZESSERYETAL.
:InhibitionandResponseLatency67cy=8.
4ms).
Withbicuculline,theresponseratein-creasedbyafactorof6butneitherthelatencynoritsvariabilitychangedmuch(SD=0.
6ms,medianlaten-cy=8.
7ms).
TheunitinFigure8L–Nshowedonlysmalleffectsofbothbicucullineandstrychnineonresponsela-tency(seealsoFig.
6C,D).
Theunit'scontrolre-sponsewasweak,partlyaresultofinhibitionoccurringathigherstimuluslevels.
Medianrstspikelatencywas10.
7ms,withlittlevariation(SD=1.
2ms).
Withstrychnine,theresponselevelroughlydoubled,butrst-spikelatencyremainednearlythesamewithlittlevariation(SD=1.
3ms,medianla-tency=10.
6ms).
Withbicuculline,theresponserateincreasedfurther,butthemedianrst-spikelatencydecreasedtoonly9.
8ms(SD=1.
5ms).
DISCUSSIONThisstudyfocusedontheroleofGABAandglycin-ergicinputinregulatingtherst-spikeresponsela-tenciesofICneurons.
Inbothspeciestested,inhibitionhadpronouncedeffectsonthedurationandmagnitudeofresponses,aswellasontheshapesofintensity–ratefunctions,butonlymodesteffectsonresponselatency.
Themajorityofneuronsshowedlatencyshiftsof5ms)inresponselatencywereob-servedintheguineapig(LeBeauetal.
1996),theywerespecicallyassociatedwithneuronswithsus-tainedresponses.
Neuronselicitingphasicburstsatonsettypicallyshowedlesschange.
ParkandPollak(1993)alsonotedthelargestlatencychangesinneuronswithsustaineddischargesandsuggestedthatitwasbecauseGABAergicdisinhibitionallowstheirrstspikestooccurinatightertemporalregister,therebydecreasingtheiraverageresponselatencies.
Thiswouldsuggestthatinhibitiondecreasestheoverallresponsivenessofthesetonicrespondersbutdoesnotnecessarilydeterminerst-spikelatency.
Incontrasttothesemodesteffects,ParkandPollak(1993)reportedthat17%ofneuronsinthehyper-trophied60kHzrepresentationofmustachedbatICshoweddecreasesrangingfrom5to25ms.
NeuronswiththelargestdecreasesinlatencywereOFFre-sponders(neuronsthatrespondedonlyattheendofastimulus)thatwereconvertedtoONresponderswhendisinhibited.
Suchneuronscanbediscountedfromthepresentdiscussionsincetheirresponsela-tenciesaredependentonstimulusduration,andla-tencychangesobservedfollowingdisinhibitionwillFIG.
8.
Representativeexamplesofthepoststimulustimehistogramsofneuronsfromthepallidbat(leftcolumn)andmustachedbat(rightcolumn)beforeandduringdisinhibition.
Theverticaldashedlinesshowmeanrst-spikelatenciesinthepallidbatandmedianrst-spikelatenciesinthemustachedbatfordifferentconditions(seetext).
Allneuronsweretestedwithstimulusparametersthatevokedthegreatestresponsesandshortestresponselatencies.
Forthepallidbat(leftcolumn)allweretestedwithbestfrequencytonesat15–20dBaboveresponsethreshold.
Sincetwooftheseneurons(A,BandE–G)weredurationselective,theyweretestedattheirbestdurationsof5and1ms,respectively.
TheneuroninC,Dwastestedwitha10msdurationtone.
FUZESSERYETAL.
:InhibitionandResponseLatency69alsodependuponstimulusduration.
However,thiscannotaccountforallofthelargedecreasesobservedinthemustachedbat.
AtrendnotedbyParkandPollak(1993)isthatneuronsinthedorsalpartofthe60kHzrepresentationintheIChadthelongestla-tencies(seealsoHattoriandSuga1997),andthispopulationshowedthegreatesteffectofdisinhibitiononresponselatency.
Presentresultsfromneuronsinthemustachedbat's60kHzrepresentationshowin-dicationsofasimilartrend(Fig.
6B);thelongestla-tencyneuronstunedto60kHzweretheonlyonestoshowlatencydecreasesof3msormorefollowingremovalofinhibition.
Ifmore60kHzneuronswithlongerresponselatencieshadbeenincluded,ourresultsmightbemoresimilartothoseofParkandPollak.
Therewasnoevidenceofthistrendamongneuronstunedinthe72–95kHzrangeinmustachedbats,orinthepallidbat(Fig.
6A).
Basedontheirdata,ParkandPollak(1993)pro-posedthatGABAergicinhibitionshapeslatencymapsthroughoutthetonotopicallyorganizedIC.
Theyfurthermoreproposedthattheorganizationofla-tencyintheICcouldprovidedelaylinesnecessaryfortheconstructionofcoincidencedetectorsselectiveforpulse-echodelay(seealsoSaitohandSuga1995;HattoriandSuga1997).
Althoughtherangeofla-tenciesinthe60kHzrepresentationofthemus-tachedbatICisnotunusual,norisitsorganizationoflatency,thedependenceoflatencyoninhibitionisremarkable.
Thisledtospeculationthatthedepen-denceoflatencyoninhibitionisaspecializedfeatureusedbythemustachedbatfortheconstructionofcoincidencedetectorstoanalyzesonarechoes(LeBeauetal.
1996).
However,resultsofseveralrecentstudiesshowthat(1)coincidencedetectorsarecre-atedintheIC,notinthemedialgeniculatebodyastheseproposalsrequire(MittmannandWenstrup1995;WenstrupandLeroy2001);(2)latencymapsintheIChavenoapparentrelationshipwiththedelaytuningofcoincidencedetectorsintheIC(PortforsandWenstrup1999,2001;Wenstrupetal.
1999);and(3)amongthedelay-tunedneuronsrecordedfromthemustachedbat'sICinthepresentstudy(withBFsof72–89kHz),neitherGABAergicnorglycinergicinhibitionappearstocontributesignicantlytothelatencyofresponsetoBFsignals.
Moregenerally,thepresentresultsinbats,asinothermammals,showthatGABAergicandglycinergicinhibitionsdonotcontributesignicantlytoresponselatencyinthegreatmajorityofthepopulationofICneurons.
MechanismsshapingresponselatencyAshorteningofresponselatencyfollowingtheblockadeofGABAaorglycinereceptors,regardlessofthemagnitudeoftheeffect,indicatesthatashort-latencyinhibitoryinput,eitherprecedingorcoin-cidingwiththearrivalofexcitatoryinput,isabletocounterdepolarizationanddelayspikegeneration(ParkandPollak1993;Halpeaetal.
1994;SaitohandSuga1995;CassedayandCovey1995).
PrecedingIPSPsintheIChavebeenobservedinwhole-cellpatch-clamp(Coveyetal.
1996)andintracellular(NelsonandErulkar1963;Kuwadaetal.
1997)re-cordingsaswellasintracellularbrainslicerecordings(Smith1992;Wagner1996;Lietal.
1999).
TheseearlyIPSPswereobservedevenwhenaneuronwaspresentedwithitsmostexcitatorystimulus(Cassedayetal.
1994;Coveyetal.
1996).
Inadditiontoinu-encingtheonsetofaresponse,inhibitionalsoshapesitsdurationandoffset,sinceblockinginhibitionof-tenconvertsneuronswithphasicresponsestotonicresponderswhoseresponsedurationslastwellbeyondthestimulusduration(e.
g.
,Fig.
8).
Thislattereffectofdisinhibitionistypicallymoreprofoundthantheeffectonrst-spikelatency.
Inadditiontodecreasingresponselatency,block-inginhibitoryreceptorscanalsoincreaselatencybyupto3ms.
Inthepresentstudyofthepallidbat,thisoccurredonlywhenglycinergicinputwasblocked.
Inthemustachedbat,thisoccurredfollowingblockadeofeitherglycinergicorGABAergicinput.
Inbothspecies,neuronswereobservedthatshowedde-creasedlatenciesinresponsetobicucullineandin-creasedlatenciesinresponsetostrychnine.
Otherstudies(ParkandPollak1993;Luetal.
1997)haveobservedthiswhenblockingGABAergicinput.
Whyresponselatenciesshouldincreaseduringdisinhibi-tionisnotclear.
Onepossibilityisthatinhibitoryin-putsthemselvesaresubjecttoinhibition,andareleasefromthisinhibitionwouldallowtheinhibi-toryinputtoexertagreaterinhibitoryeffectontherecordedneuron.
If,forexample,alocalGABAergicinhibitoryneuronclosetothesiteofdrugapplicationreceivedinhibitionfromaglycinergicinput,thentheapplicationofstrychninewouldreleasetheinhibitoryneuronfrominhibition,allowingittoexertagreaterinhibitoryeffectontherecordedneuronandin-creaseitsresponselatency.
Asecondpossiblemechanismisthatareboundfrominhibitionmaycontributetoexcitationinsomeneurons.
Thus,eliminationofanearlyinhibitioncouldslowdepolarizationandincreaselatency.
In-creasedexcitationfollowinghyperpolarizationhasbeenreportedinvitrointhecochlearnucleus(Manis1990)andinthedorsalnucleusofthelaterallem-niscus(WuandKelly1995),aswellasintheIC(Smith1992;Perruzietal.
2000).
Invivo,basedonwhole-cellpatch-damprecordings,Cassedayetal.
(1994)haveproposedthatareboundfromearlyin-hibition,coincidingwitharrivalofalateexcitatoryinput,mayunderlieaselectivityforsoundduration70FUZESSERYETAL.
:InhibitionandResponseLatencyobservedintheICofthebigbrownbat.
Additionalevidencethatinhibitionmaycontributetoexcitationintheinferiorcolliculuscomesfromarecentstudyofcombination-sensitiveneuronsinthemustachedbat(WenstrupandLeroy2001).
Thefacilitatedresponseproducedbyappropriatecombinationsoftonesiseliminatedbyblockinginhibitoryglycinergicinput.
Thisparadoxicalresultcouldbetheresultofblock-ingapostinhibitoryreboundthatcontributestoex-citation.
Inhibitioncanindeedinuencetheresponsela-tencyofICneurons,but,withtheexceptionoflong-latencyneuronsinthemustachedbat(ParkandPo-llak1993),therathersmalleffectsobservedinotherspeciesafterblockinginhibitioncannotaccountforthewiderangeoflatenciespresentinthemidbrain.
Othermechanismsrequiregreaterattention.
Wavepropogationtimesalongthecochlearbasilarmem-branecancontributetoashort,frequency-dependentdelayofaround1ms,withhigher-frequencyinputarrivingrst(RhodeandSmith1986).
TheinuenceofthiscochleardelayonICresponselatenciesismostlikelyinsignicant,particularlyinthelateralregionofthepallidbatIC,whereneuronswithlowbestfre-quencieshavetheshortestresponselatencies.
Whiletherangeoflatenciesatlowfrequencieshasbeenfoundtobebroader,minimumlatencieshavebeenfoundtobelargelyindependentoffrequencytuning(e.
g.
,LangnerandSchriener1988;Halpeaetal.
1994).
Otherfactorsthatcaninuenceresponselatencyareaxonlength,conductionvelocity,thenumberofsynapsesalonganascendingpathway,andsynapticintegrationtimes.
ThecontributionofeachofthesefactorsinICresponselatenciesislikelytovaryacrossneurons.
Forexample,studiesthatusedelectricalstimulationoftheauditorynerve(Snyderetal.
1995)anddorsalcochlearnucleus(SempleandAitkin1980)inplaceofnormalacousticstimulationreportawiderangeofresponselatenciesintheIC,leadingtotheconclusionthatitisunlikelythataxonlengthsorthenumberofintercalatedsynapsescouldaccountfor10–20msdifferencesinresponselatenciesintheIC(Snyderetal.
1995).
Theincreaseinresponsela-tenciesalongtheaxisoftheIC(e.
g.
,LangnerandSchriener1988;HattoriandSuga1997)isdifculttoaccountforthroughadditionaltraveltime.
ThissamegradientofresponselatencieswasobservedinthepallidbatIC,wheremorethan10msincreasesinlatencyoccuroveraseparationofonly1.
5mm.
Instead,muchofthedelayinresponseonsetmayresideinmechanismsthatareintrinsictotheIC.
IntracellularbrainslicerecordingsoftheICC(Wag-ner1996)reportlongresponselatencies(to12ms),evenwhenneuronsareexcitedbyelectricalstimula-tionofthelaterallemniscusimmediatelyventraltotheIC.
InthecorticesofthecatIC,regionsthatre-ceiveprimarilyintracollicularandneocorticalinputs,excitatorypostsynapticpotentials(EPSP)latenciesofupto11mswerereportedfollowingstimulationofthecommissureoftheIC(Smith1992).
Theselonglatenciesfollowingintracollicularelectricalstimula-tionsuggestthatmultisynapticcircuitsand/orlongsynapticintegrationtimeswithintheICcanpoten-tiallyimposeadelayinresponsethatcanbelongerthanthetimerequiredforthetransmissionofin-formationfromthecochleatotheIC.
Indeed,Halpeaetal.
(1994)emphasizedthat,inthebigbrownbat,theminimumresponselatenciesfromthelevelsofthecochlearnucleustothelaterallemniscalnucleitotheICdonotincreaseappreciably.
Rather,itistherangeofresponselatenciesthatincreasesdramati-callyasoneascendstheauditorybrainstem.
OnemechanismthatmaycontributetothewidelatencyrangeisadifferenceinthetypesofexcitatoryandinhibitoryreceptortypesacrosstheICandthemannerinwhichtheyinteracttocontrolthetimingofsynapticintegration.
AMPAandNMDAglutamatereceptors,forexample,arereportedtoactivatefastandslowpostsynapticexcitatorypotentials,respec-tively(Yangetal.
1999;KellyandKidd2000;ZhangandKelly2001).
Similarly,GABAaandGABAbre-ceptorsappeartoberesponsibleforinhibitorypo-tentialswithdifferenttimecourses(CrunelliandLeresche1991),andarereportedtobedifferentiallydistributedacrosstheIC(Vateretal.
1992;Fubaraetal.
1996).
SincethepresentstudyexaminedtherolesofonlyfastinhibitoryeventsmediatedbyGABAaandglycinereceptors,thepossiblerolesofotherreceptortypesmediatingslower,longer-lastingexcitatoryandinhibitoryeventsinshapingresponselatencywerenotrevealed.
Inconclusion,thisreportdoesnotquestiontheimportanceofinhibitioninregulatingthetimingofresponsesinthecentralauditorysystem.
Thereisgrowingevidencethatthetimingofinhibitoryandexcitatoryinputsplaysanimportantroleinshapingresponseselectivityfortemporalfeatures,suchasduration,andforcomplex,behaviorallyrelevantsounds,particularlythosewithcomponentsthataredelayedintime.
Moreover,neuronswithOFFre-sponsesduetoinhibitionimposedduringthecourseofasoundwillexhibitlongdelaysthatvarywithsoundduration.
Rather,thepresentstudyexaminedICneuronsthatrespondedatsignalonset,someofwhichhadlongrst-spikelatencies(10–25ms)thatfarexceededtheminimumtimerequiredforinputtotheIC.
Weaskedwhethertheselatenciescouldbefurtherdecreasedbytheblockadeofinhibitoryin-putswhencarehadbeentakentoensurethatthesoundspresentedevokedresponsesattheshortestpossiblelatenciespriortodisinhibitionbyinhibitoryFUZESSERYETAL.
:InhibitionandResponseLatency71transmitterblockers.
Despitelargeeffectsonre-sponsemagnitudeandduration,theblockadeofGABAaandglycinereceptorstypicallyproducedsmallchangesinresponselatency(<1ms).
Thisnding,coupledwiththosefrommostspecies,sug-geststhatfastinhibitorypathwaysmaynotplayadominantroleincreatingthewiderangeofresponselatenciesobservedinthemammalianIC.
ACKNOWLEDGMENTSWethankCarolGrosefortechnicalassistanceandTerriZumstegforeditingthemanuscript.
WearegratefultotheWildlifeSectionoftheMinistryofAgriculture,Land,andMarineResourcesofTrinidadandTobagoforpermissiontoexportmustachedbats.
ResearchwassupportedbyfundsfromtheNationalInstitutesofHealth(RO1DC00054toZMFandRO1DC00937toJJW)andtheNationalScienceFoundation(IBN-9828599toZMF).
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