Different effects of unexpected changes in environmental conditions on prepulse inhibition in rats and humans

Di e en e ec s o unexpec ed changes in en i onmen al condi ions on p epulse inhibi ion in a s and humans L.G. De la Casa1, A. Fe nandez1, J. La au i2, A. Mena1, A. Puen es1, E. Quin e o1, and N. Schmajuk2 1 Depa men o Expe imen al Psychology, Uni e si y o Se ille, 41018 Se ille, Spain 2 Depa men o Psychology and Neu oscience, Duke Uni e si y, Du ham, NC 27708, Uni ed S a es Add ess co espondence o: L.G. De la Casa Dp . Psicologia Expe imen al Facul ad de Psicología C/ Camilo José Cela, s/n 41018 Se illa (Spain) Tel.: (34) 954557682 Fax: (34) 954551784 E-mail: [email p o ec ed] Abs ac The educ ion o he s a le esponse o an audi o y s imulus caused by he p esen a ion o ano he s imulus o lowe in ensi y closely p eceding i , a phenomenon known as p epulse inhibi ion (PPI), can be modula ed by changes in dopamine gic ac i i y. Schmajuk, La au i, De la Casa, and Le in (2009) demons a ed ha his dopamine gic modula ion o PPI in a s can be in luenced by manipula ing he expe imen al con ex , speci ically by in oducing changes in he ambien ligh ing condi ion ha include no el elemen s. In his pape we analyse he e ec s o in oducing changes in con ex illumina ion on PPI in male a s (Expe imen 1) and humans (Expe imen 2). The esul s wi h a s showed a educ ion o PPI when he illumina ion condi ion swi ched om da k o ligh , bu no om ligh o da k. In he expe imen wi h human pa icipan s he educ ion o PPI occu ed o bo h changes in illumina ion condi ions. The animal expe imen esul s a e in e p e ed in e ms o compe ing explo a o y beha io ha appea when he con ex is illumina ed a e he da k- ligh ansi ion; while in he case o human pa icipan s a pe cep ual and/o a en ional mechanism a e bo h illumina ion ansi ions is p oposed, which may esul in a educed p ocessing o he p epulse and subsequen lowe PPI. Keywo ds: P epulse inhibi ion; No el y; Dopamine; Ra s; Humans. 1. In oduc ion. The s a le esponse includes, among o he beha io s, he in olun a y con ac ion o he skele al muscles and occu s a e he p esen a ion o a s imulus o some in ensi y [1,2]. Typically, he s a le esponse is assessed by quan i ying he in ensi y o muscle con ac ion a e he s imulus p esen a ion. The s a le esponse is suscep ible o modula ion h ough a ious manipula ions such as he epea ed p esen a ion o he s imulus, which can lead o habi ua ion o sensi iza ion o he esponse [3,4], he induc ion o a pa icula emo ional s a e p io o s imulus p esen a ion [5,6] o o changes in en i onmen al condi ions in which he s imulus is p esen ed [7]. Ano he o m o modula ion o he s a le esponse ha has ecei ed much a en ion om esea che s in he ield o psychophysiology in he las decades is p epulse inhibi ion (PPI), a phenomenon ha occu s when a s imulus o lowe in ensi y p ecedes he p esen a ion o a s a ling s imulus, esul ing in he educ ion o he esponse o he la e [8]. The occu ence and in ensi y o PPI depends on a numbe o a iables such as he ime in e al be ween he p epulse and pulse s imuli [9], hei in ensi y [10] o he backg ound noise le el in which he s imuli a e p esen ed [11]. PPI is belie ed o e lec senso imo o ga ing abili ies, i.e., he abili y o espond o po en ially ele an s imuli, simul aneously inhibi ing he p ocessing o o he s imuli and/o esponses ha migh hinde he in-dep h p ocessing o a s imulus unde analysis [12]. Acco ding o his poin o iew, PPI would e lec an e ec i e inhibi ion o he mo o esponse o he s imulus o g ea e in ensi y (pulse), ensu ing an in-dep h analysis o he p epulse s imulus (which p eceded he pulse p esen a ion), and hus ep esen ing a simple example o senso imo o modula ion [13]. The neu al ci cui y ha egula es bo h he s a le esponse o audi o y s imuli as well as PPI has been cha ac e ized in de ail [8]. The neu al sys ems o bo h he s a le esponse and PPI a e modula ed by a numbe o neu o ansmi e s such as dopamine, GABA, glu ama e and ace ylcholine, which egula e he magni ude o he s a le esponse and i s inhibi ion [8]. Zhang e al. [18] s udied he e ec o indi ec dopamine (DA) agonis s on PPI in a s, and showed ha amphe amine adminis a ion esul ed in a dec ease in he magni ude o PPI. S udies wi h schizoph enic pa ien s, a diso de cha ac e ized among o he hings by a hype ac i i y o he dopamine gic sys em, suppo he hypo hesis ela ing ele a ed dopamine elease wi h PPI a enua ion [21]. In addi ion o pha macological manipula ions, he e a e en i onmen al changes ha can cause changes in dopamine gic ac i i y, such as he exposu e o a no el s imulus o con ex [22,23]. An inc ease in co ical dopamine gic ac i i y in a s indica es ha a no el s imulus is p esen ed o he animal, an e ec ha is no ound wi h neu al o habi ua ed s imuli [24]. Wi h ega ds o he subco ical dopamine sys em, he elease o dopamine in he nucleus accumbens is ela ed o he pe cep ion o no el y [25]. Acco ding o he esul s p esen ed abo e, ex e nal changes in ol ing he in oduc ion o new elemen s in he expe imen al si ua ion, such as a manipula ion o he illumina ion condi ion in he a ea whe e he subjec is loca ed, would impac he dopamine gic ac i i y and p oduce a modula ing e ec on PPI [26]. Ou aim in his pape is o analyze he e ec ha en i onmen al changes –namely, a a ia ion in he illumina ion condi ions- ha e on he s a le esponse and PPI in bo h a s and humans. Based on he esul s epo ed by Schmajuk e al [26] we expec ha exposu e o no el en i onmen al si ua ions would p oduce a ansien inc ease in dopamine elease in bo h co ical and subco ical egions [24] and he e o e cause a educ ion in PPI in bo h a s and humans. Howe e , i is possible ha he e ec s on PPI may depend on he ype o no el s imulus ha appea s in he expe imen al si ua ion, since p e ious esul s wi h a s indica e ha PPI is educed a e a da k o ligh ansi ion, bu no when he change is om ligh o da k [26]. I is possible ha his lack o symme y in animals is es ic ed o he ansi ion om da k o ligh due o he inc ease in su ounding isual s imuli ha occu s wi h a sudden illumina ion inc ease. 2. Expe imen 1 The i s expe imen is designed o ep oduce he esul s ob ained by Schmajuk e al. [26], namely he educ ion o he s a le esponse and PPI a e a change o illumina ion in he expe imen al condi ion. Some changes o he Schmajuk e al. [26] design we e in oduced in his expe imen : i s , a 90 dB SPL p epulse was used ins ead o a 70 dB SPL s imulus, since in pilo s udies in ou labo a o y no consis en PPI was ound wi h he la e p epulse in ensi y. A second majo change was he use o male a s in ou expe imen , hus elimina ing he sou ce o a iabili y ela ed o he ho monal changes ha occu pe iodically in emale a s in es us unc ion [27], ha ha e been shown o in luence PPI [28]. Thi d, in ou expe imen s Wis a a s we e used, ins ead o he Sp ague-Dawley s ain es ed in Schmajuk e al. [26]. Fou h, in ou expe imen he animals we e main ained unde a egula ligh -da k cycle, ins ead unde a e e sed cycle ( hus, in ou expe imen he animals we e es ed in hei ligh phase). A inal impo an change in he design was ha his expe imen used a be ween-subjec s design in which each g oup o animals ecei ed only one o he en i onmen al changes (ligh o da k [L/D] o da k o ligh [D/L]) e sus he wi hin-subjec design used in Schmajuk e al. [26]. Based on he p e ious esul s ob ained by Schmajuk e al. [26], we expec ha he illumina ion change would p oduce an a enua ion o PPI, bu only when he change in ol es a ansi ion om da k o ligh . 2.1. Me hod 2.1.1. Subjec s Six een male Wis a a s, expe imen ally naï e, pa icipa ed in his expe imen . The mean weigh a he s a o he expe imen was 342 g . ( ange 297-410). Food and wa e we e a ailable ad libi um h oughou he expe imen . Ra s we e indi idually housed in he colony wi h a egula ligh -da k cycle o 12:12 hou s. All es ing occu ed du ing he 12-h ligh pe iod (s a ing a 10:00 AM). Fou days be o e he s a o he expe imen al sessions, each o he animals was handled 5 minu es daily. 2.1.2. Appa a us and s imuli Fou Panlab chambe s (model LE 111) designed o de ec and eco d he s a le esponse in a s we e used. Each chambe was enclosed in a sound- p oo module (model LE 116), and inside each chambe a pe spex cylinde o 8 cm in diame e was a ached o he loo o he expe imen al chambe , es ing on a pla o m ha egis e ed and eco ded each animal’s mo emen . A loudspeake was p esen a he op o each chambe , which p oduced a cons an backg ound whi e noise o 65 dB SPL. The pulse s imulus was a 20 ms, 120 dB SPL whi e noise, and he p e-pulse was a 20 ms, 90 dB SPL whi e noise. The lead in e al in he p epulse-pulse ials was 100 ms, and he in e - ial in e al was 30 sec (+/- 5). A 24V, 2W key ligh (ligh in ensi y o app oxima ely 180 lx) was loca ed on he le side o he chambe . Vib a ions o he Plexiglas enclosu e caused by he whole-body s a le esponse o he animal we e con e ed in o analog signals by a piezoelec ic uni a ached o he pla o m. These signals we e digi ized and s o ed by a compu e as a linea pa ame e . The a e age s a le ac i i y was measu ed in a 100-ms ime window s a ing a he onse o he sound s imulus, whe eas he a e age baseline ac i i y was measu ed by selec ing he highes esponse in he in e al be ween ials. 2.1.3. P ocedu e Fo he L/D g oup (n = 8) he key ligh inside he expe imen al chambe was on om he beginning o he expe imen , while in he case o he D/L g oup (n = 8) he key ligh was o . Once he a s we e in oduced in he expe imen al chambe s, hey wen h ough a 5-minu e acclima ion pe iod in which he only audi o y s imula ion p esen ed was he cons an 65-dB SPL backg ound noise, which emained h oughou he expe imen . Following he acclima ion pe iod, 4 pulse-alone s imuli we e p esen ed wi h a mean in e - ial in e al ITI o 30 sec. A e 6.5 addi ional minu es, 6 pulse-alone and 6 p epulse-pulse ials we e andomly p esen ed, wi h a mean ITI o 30 sec (+/- 5). In p epulse-pulse ials he in e al be ween he p epulse and pulse was 100 ms. Following his sequence o ials, he change in ligh ing condi ion (ligh o da k o ice e sa, depending on he g oup) was in oduced, and he same 6 pulse-alone and 6 p epulse-pulse ial sequence was p esen ed. 2.1.4. Resul s A p elimina y 4 x 2 ANOVA (T ials x Condi ion: D/L s. L/D) conduc ed on mean s a le esponses o he 4 pulse-alone ials p esen ed a he beginning o he session e ealed no signi ican main e ec s o in e ac ions (all ps>.19) Figu e 1 shows s a le esponses (exp essed in a bi a y uni s) o pulse- alone and p epulse-pulse ials du ing he expe imen al phase. I also shows mean esponse du ing in e ial in e als (no s imulus ials) compu ed by collapsing he maximum spon aneous esponse by con iguous Pulse and P epulse-pulse ITIs. Panel A p esen s he s a le esponses o a s in g oup L/D, in which he i s block o ials ook place wi h he key ligh on, and he second block wi h he key ligh o . Panel B shows he esul s o a s in g oup D/L, in which he illumina ion condi ions we e e e sed. As seen in bo h panels o Figu e 1, du ing he i s block he di e ence be ween esponses o pulse- alone and p epulse-pulse ials (i.e., PPI) emained cons an . Howe e , he in oduc ion o changes in illumina ion condi ions had a di e en ial e ec on he s a le esponse in pulse-alone ials: while no change was obse ed in g oup L/D (Panel A), PPI disappea ed ansien ly in g oup D/L du ing he i s ials in he p esence o ligh (immedia ely a e he ansi ion) o g adually eco e o e he emaining ials (panel B). The esponses du ing he no-s imulus pe iods emains low and s able ac oss he en i e du a ion o he expe imen , hus disca ding any possible loo e ec o he s a le esponse on he expe imen al ials, bu showing a gene al inc ease a e he illumina ion ansi ion. ----------------------------------------- Figu e 1 abou he e ----------------------------------------- These imp essions we e con i med by a subsequen s a is ical analysis. Speci ically, a 6 x 2 x 2 x 2 ANOVA es (T ials x T ial ype: pulse-alone s. p epulse-pulse x Posi ion: i s block o six ials s. second block x G oup: L/D s. D/L, wi h he i s h ee ac o s being wi hin-subjec ) on mean s a le esponses e ealed a signi ican main e ec o T ial Type, F(1,14) = 35.54; p < .001, η2 = .72, e lec ing he o e all PPI e ec . A signi ican T ials x Posi ion in e ac ion was also ound, F(5,70) = 6.77; p < .001, η2 = .33, due o a gene al end o s a le ampli ude o dec ease ac oss ials in he i s block o six ials, and o inc ease in he second block. Finally, he 3-way T ial ype x Posi ion x G oup in e ac ion was also signi ican , F(1,14) = 7.61; p < .05, η2 = .35. No addi ional signi ican main e ec s o in e ac ions be ween ac o s we e ound (all ps>.09). In o de o iden i y he sou ce o he 3-way in e ac ion, we conduc ed sepa a e 2 x 2 ANOVAs (T ial ype x Posi ion) o L/D and o D/L g oups. The ANOVA o he L/D g oup e ealed only a signi ican main e ec o T ial ype, F(1,7) = 14.05; p < .01, η2 = .66, due o he gene al e ec o PPI. The ANOVA es on mean s a le esponses o he D/L g oup e ealed a signi ican main e ec o T ial ype, F(1,7) = 21.95; p < .01, η2 = .77, due o he PPI e ec , and a end owa d a signi ican T ial ype x Block in e ac ion was ound, F(1,7) = 4.84; p = .064, η2 = .35. The in e ac ion e lec s a end owa ds a lowe s a le esponses in pulse-alone ials in he i s block o ials (mean = 42.24, SEM = in e ac ion was also signi ican , F(3,66) = 3.26; p < .05, η2 = .13, e lec ing he o e all dec ease o he s a le esponse ac oss ials due o habi ua ion in he p e- ansi ion block ha did no appea in he pos - ansi ion ials, whe e he s a le esponse was al eady habi ua ed. No addi ional main e ec s o in e ac ions we e ound o be signi ican (all ps>.11). Figu e 2 shows mean s a le esponses o pulse-alone and p epulse- pulse ials, exp essed in a bi a y uni s. Panel A p esen s he s a le esponse o g oup D/L ( he i s ials in da kness and he las es s in he p esence o ligh ), while Panel B shows hese esponses o g oup L/D (wi h he i s six ials in he p esence o ligh and he las six in he da k). In bo h cases, he esponse pa e n was simila , wi h mo e in ense esponses in he i s six pulse- alone ials compa ed o p epulse-pulse ials ( e lec ing he PPI) and an inc ease in esponse o p epulse-pulse ials in he second block o ials, a e he in oduc ion o he illumina ion change ( om ligh o da k o om da k o ligh ). -------------------------------------- Figu e 2 abou he e -------------------------------------- A mixed 6 x 2 x 2 x 2 ANOVA (T ials x T ial ype: pulse-alone s. p epulse-pulse x Posi ion: i s block o six ials s. second block x G oup: L/D s. D/L, he i s h ee ac o s being wi hin-subjec ) e ealed signi ican main e ec s o T ials and T ial ype, F(5,110) = 8.67; p < .001, η2 = .29, and F(1,22) = 32.44; p < .001, η2 = .60, espec i ely. The main e ec o T ials e lec s a gene al dec ease o he s a le esponse ac oss ials due o a habi ua ion p ocess; he main e ec o T ial ype was due o an o e all PPI e ec , wi h highe s a le esponse o pulse-alone han p epulse-pulse ials (mean = 0.56, SD = 0.38, and mean = 0.42, SD = 0.30, espec i ely). The T ials x T ial ype in e ac ion was also signi ican , F(5,110) = 2.36; p < .05, η2 = .10, e lec ing a dec ease o s a le in ensi y ac oss ials o he Pulse-alone, bu no o he P epulse-Pulse ials. The T ial ype x Posi ion was also signi ican , F(1,22) = 14.39; p = .001, η2 = .40, due o he PPI e ec ob ained in he i s block o ials ha anished on he second block. Finally, he T ials x T ial ype x Posi ion in e ac ion was signi ican , F(5,110) = 4.06; p < .01, η2 = .16. An explo a ion o his 3-way in e ac ion e ealed i was due o a dec ease ac oss ials o he PPI e ec on he i s block o ials, and an absence o such PPI e ec on he second block o ials. No addi ional main e ec s o in e ac ions we e ound o be signi ican (all ps>.16) 4. Discussion The esul s o bo h expe imen s show ha he p esen a ion o a no el s imulus, speci ically he in oduc ion o a change in ambien illumina ion condi ions, has an impo an e ec on he s a le esponse and PPI. In he i s expe imen we ound ha he s a le esponse o a s in pulse-alone ials dec eases as a esul o no el y –bu only a e he change was om da k o ligh -, causing a dec ease PPI. In Expe imen 2, changes in illumina ion condi ions – ega dless o hei di ec ion- caused an inc ease in he s a le esponse on p epulse-pulse ials in humans, and a consequen dec ease in PPI. Al hough yielding a simila ou come in e ms o PPI educ ion, he esul s o bo h expe imen s a e clea ly di e en a ending o he way in which changes in en i onmen al condi ions a ec he s a le esponse in pulse-alone and p epulse-pulse ials. The esul s o animal expe imen s ep oduce exac ly hose ob ained by Schmajuk e al. [26], namely he dec ease in s a le esponse in pulse-alone ials. Al hough ou Expe imen 1 did no o e any di ec neu obiological da a, he beha io al da a a e consis en wi h he hypo hesis ha conside s he obse ed s a le educ ion o he pulse media ed by he elease o dopamine in he NAC induced by he in oduc ion o a no el s imulus ( he change in ambien illumina ion). Acco ding o his iew, he ac i a ion o he dopamine gic sys em would lead o he de elopmen o explo a o y beha io s ha would compe e wi h he gene a ion o s a le esponses in pulse-alone ials, hus dec easing hei ampli ude [26]. Se e al indings suppo his hypo hesis: Fi s , he e is expe imen al e idence showing ha inc eased explo a o y beha io is nega i ely co ela ed wi h he in ensi y o he s a le esponse o in ense s imuli [32]; in addi ion, se e al s udies ha e e ealed ha con ex ual changes in ol ing no el y a e posi i ely co ela ed wi h inc eased dopamine elease in he NAC [33,34]. Thus, when Sp ague-Dawley a s we e exposed o an un amilia no el en i onmen , an inc ease o dopamine loca ed in he NAC ha pe sis s o abou 25 seconds was obse ed [35] Rebec e al. (1997). Using mic odialysis s udies, dopamine elease in he NAC inc eased when Long- E ans a s we e exposed o an en i onmen con aining no el objec s [36]. Such phasic dopamine inc ease seems o be linked o he ac i i y o neu ons in Ven al Subiculum (VS), since neu ons in his egion ac i a e glu ama e ecep o s in he VTA (Ven al Tegmen al A ea) ha esul s in an inc ease o dopamine in he NAC o no el s imuli. The e is also he possibili y ha VS di ec glu ama e gic p ojec ions o neu ons o he NAC induce an inc ease in dopamine o no el y, o ha i is ela ed o a ci cui in ol ing VS p ojec ions o he p e on al co ex, which in u n in ol es glu ama e gic p ojec ions o VTA [36]. In he case o change in he ambien illumina ion condi ion om ligh o da k, i is possible ha he explo a o y beha io s ha compe e wi h he s a le esponse in pulse-alone ials do no appea since he numbe o isual s imuli a ailable o explo a ion in his condi ion dec eases. This possibili y was con i med by he analysis o explo a o y beha io conduc ed on wo ials be o e and a e he illumina ion change: an inc ease in explo a o y beha io was obse ed only in he Da k- o-Ligh g oup. The esul s o Expe imen 2 wi h human pa icipan s exhibi a di e en pa e n om hose ob ained wi h animals. Fi s , he PPI educ ion e ec a e he in oduc ion o he illumina ion change was symme ical, i.e., i was obse ed in changes om da k o ligh as well as om ligh o da k. A second impo an di e ence wi h he esul s ob ained in he expe imen wi h a s is ela ed o he o igin o he obse ed educ ion in PPI. While o oden s PPI dec eased as a consequence o a educ ion o he s a le esponse in he i s pulse-alone ials a e he in oduc ion o he en i onmen al illumina ion change, in humans he educ ion was due o an inc ease in s a le esponses in he i s p epulse-pulse ials ollowing he illumina ion change. An addi ional di e ence be ween a s and humans esul s is ela ed o he leng h o he e ec ha was es ic ed o he i s wo ials in he expe imen wi h a s, bu ex ended ac oss he six pos - change ials in he expe imen wi h humans. Howe e , as can be seen in Figu e 2, he s a le educ ion o he Pulse, p obably due o habi ua ion, had con ibu ed o he appa en a enua ion o PPI. The e o e, acco ding o he expe imen al esul s, he cause o he obse ed PPI educ ion in humans is necessa ily di e en om ha obse ed in oden s, since all changes (no only ha induced by he eme gence o no el s imuli in he en i onmen in oduced in he ligh condi ion, bu also he change caused by he disappea ance o cues when he ligh was u ned o ) educed PPI. An impo an ac o o conside when analyzing hese di e ences is ela ed o he magni ude o he ligh sou ce used in he expe imen s wi h oden s and humans. While in Expe imen 1 he s imulus used was a 2 W ligh , in he case o Expe imen 2 a 36 W LED bulb loca ed 100 cm abo e he head o he pa icipan s was employed. I is possible ha he illumina ion p o ided in he oden ’s case could ha e acili a ed he appea ance o an o ien ing esponse o he no el s imuli, causing he obse ed educ ion in PPI [26], whe eas in he human expe imen , he mo e salien ligh could ha e launched pe cep ual and/o a en ional p ocesses in addi ion o he ones exhibi ed by oden s. Thus, a possible explana ion –albei specula i e- o ou esul s, is ha he in oduc ion o se e e en i onmen al changes in he human expe imen may ha e empo a ily changed he de ec ion h eshold o audi o y s imuli. Using di e en p epa a ions o he ones employed in he p esen expe imen s (e.g., c oss-modal oddball asks), e idence o he e ec s o p esen ing dis ac ing s imuli on he p ocessing o s imuli o di e en senso y modali y wi h human pa icipan s has been epo ed. Thus, using mainly audi o y [37] and ac ile [38] s imuli, hese esea che s showed he exis ence o wha hey call “pos -no el dis ac ion”, a p ocess ha e lec s he need o edi ec a en ional esou ces om a no el o a a ge s imulus in he expe imen al si ua ion [39]. Al hough admi edly specula i e, in addi ion o his dis ac ing e ec , he in oduc ion o changes in ambien illumina ion condi ions in Expe imen 2 may igge a second e ec ela ed o he a en ional shi caused by he p esen a ion o an unexpec ed isual s imulus, which would slow he p ocessing o an audi o y s imulus appea ing immedia ely a e wa ds [40- 41]. This slowing e ec , which esul s in inc eased esponse imes in eac ion ime asks, appea s o be mo e signi ican when he s imuli p esen ed a e unexpec ed [42]. In his case, he obse ed PPI would no indica e a senso imo o ga ing e ec , bu e lec a ailu e o de ec he p epulse. F om a psychophysiological pe spec i e, he dopamine gic ac i a ion p oduced by he p esen a ion o no el s imuli can be ound on he basis o di e en esponses gi en by pa icipan s h oughou he s udy. As men ioned abo e, he e is a s ong co ela ion be ween dopamine elease in he nucleus accumbens and he no el e ec o he con ex [33,34]. 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