Dynamic shifts in the owl s auditory space map predict moving sound location

Transcription

1 6 Nture Pulishing Group Dynmic shifts in the owl s uditory spce mp predict moving sound loction Iln B Witten 1,, Joseph F Bergn 1, & Eric I Knudsen 1 The optic tectum of the rn owl contins mp of uditory spce. We found tht, in response to moving sounds, the loctions of receptive fields tht mke up the mp shifted towrd the pproching sound. The mgnitude of the receptive field shifts incresed systemticlly with incresing stimulus velocity nd, therefore, ws pproprite to compenste for sensory nd motor delys inherent to uditory orienting ehvior. Thus, the uditory spce mp is not sttic, ut shifts dptively nd dynmiclly in response to stimulus motion. We provide computtionl model to ccount for these results. Becuse the model derives predictive responses from processes tht re known to occur commonly in neurl networks, we hypothesize tht nlogous predictive responses will e found to exist widely in the centrl nervous system. This hypothesis is consistent with perceptions of stimulus motion in humns for mny sensory prmeters. Predicting the future stte of the world is essentil for generting dptive ehvior. For exmple, to orient the eyes towrd moving stimulus, n niml must predict the future position of the stimulus in order to compenste for the sustntil delys etween senstion nd motor output. Without such prediction, n niml would orient to position in spce tht lgs ehind the stimulus true position. Here we descrie neurl circuit in the rn owl s optic tectum (homolog of the mmmlin superior colliculus) tht mkes such prediction in response to the motion of n uditory stimulus. Motion hs systemtic effects on spce-dependent response properties, even in popultions of neurons tht re not tuned for the direction of motion. In the retin, moving rs of light cn cuse the sptil distriution of neurl ctivity to shift, nd the direction of the shift is pproprite to compenste for sensory delys 1. However, the mgnitude of the shift does not increse with stimulus speed, even though lrger shift is needed for the prediction to e dptive t higher speeds. In ddition, stimulus motion hs een shown to hve systemtic effects on uditory responses t vrious sites in the centrl uditory system. These studies hve shown tht the direction nd speed of moving sound chnges the spce-dependent response properties of neurons 7. In these studies, unit responses were mesured using single stimulus tht swept cross the receptive field, so tht responses to different sptil loctions were mesured t different times fter stimulus onset. Becuse uditory sptil receptive fields cn shrpen mrkedly fter stimulus onset, not controlling for time fter stimulus onset confounds onset-dependent receptive field shrpening with shifts in receptive field loction. To resolve the effects of sound motion on receptive field size nd loction, seprtely, requires tht oth receptive field edges e mesured t identicl time points following stimulus onset. Only shift in receptive field loction could id in predicting the future loctions of moving stimuli. Here, we descrie new stimulus protocol for mesuring the effect of motion on receptive field size nd loction nd demonstrte tht uditory receptive fields in the owl s optic tectum shift sustntilly following the onset of moving sound. Moreover, the time course over which receptive field shifts develop is ehviorlly relevnt nd the mgnitude of these shifts is pproprite for guiding dptive ehvior. The optic tectum is midrin structure tht prticiptes in orienting the owl s gze towrd uditory stimuli 9. The uditory system derives stimulus loction y nlyzing vrious monurl nd inurl cues. The primry cue for the horizontl position (zimuth) of sound source is interurl time difference (ITD), cused y the dely etween sound reching the ner versus the fr er 1.Theprimrycueforthe verticl position (elevtion) is interurl level difference (ILD) for high frequency components (44 khz), cused y physicl symmetry of the owl s externl ers 11,1. Neurons in the owl s optic tectum re shrply tuned for oth ITD nd ILD, nd re orgnized ccording to the cue vlues to which they re tuned, forming topogrphic mp of uditory spce 13. To test the effect of stimulus motion on uditory sptil tuning, we presented sounds through erphones (dichoticlly) nd simulted stimulus motion in zimuth with continuous chnges in ITD cues. Presenting sounds dichoticlly llowed us to rndomly interleve virtul motion sweeps of different velocities nd cross different portions of spce. Motion in zimuth is redily mimicked in quntittive nd compelling mnner ecuse, cross lrge portion of frontl spce, ITDs vry linerly with zimuth nd re consistent cross frequencies 14,15 ; indeed, sounds presented dichoticlly with constnt ITD elicit predictle zimuthl hed turns in ehving 1 Deprtment of Neuroiology, Stnford University Medicl School, Stnford, Cliforni 9435, USA. These uthors contriuted eqully to this work. Correspondence should e ddressed to E.I.K. (eknudsen@stnford.edu). Received 6 July; ccepted 1 Septemer; pulished online 1 Octoer 6; doi:1.13/nn171 NATURE NEUROSCIENCE VOLUME 9 [ NUMBER 11 [ NOVEMBER

2 6 Nture Pulishing Group c e Leftwrd motion d Rightwrd motion reltive to sound onset (ms) f owls 1. In contrst, quntittive simultion of stimulus motion in elevtion is complicted ecuse ILD vlues vry nonmonotoniclly with oth elevtion nd zimuth nd re highly frequency dependent 14,15. Hence, our nlysis ws restricted to the effects of simulted motion in zimuth. Therefore, whenever we use the term spce in this pper, we re referring exclusively to zimuth. However, ecuse elevtion, like zimuth, is represented topogrphiclly in the optic tectum, we hypothesize tht similr effects would e oserved for oth dimensions. RESULTS Moving sounds cuse predictive RF shifts We presented rndomly interleved, virtul motion sweeps tht egn t evenly spced ITD vlues spnning the receptive field of the recording site (Fig. 1,). The sounds, which swept either to the left or to the right, were presented one t time. By compiling the responses to the stimulus sweeps, we could construct neuron s sptil receptive field to moving stimuli for ny time point following sound onset tht is, neuron s sptiotemporl receptive field to moving stimuli. This nlysis demonstrted oth shrpening of receptive fields over time following stimulus onset, s well s predictive shifts in receptive field loctions. These dt llowed us to quntify the time 6 Spikes per s Figure 1 s in sptiotemporl receptive fields in response to stimulus motion ( ms ITD per s) for single optic tectum unit. ( f) Left column, leftwrd motion; right column, rightwrd motion. Horizontl lck lines in c f indicte the est ITD mesured with sttionry stimuli. (,) Ech rrow represents single moving uditory stimulus. Ech stimulus ws presented one t time in rndomly interleved fshion. The shded region indictes the portion of the mesured sptiotemporl receptive field tht is plotted in susequent pnels. (c,d) Rster plots showing the responses to the set of moving uditory stimuli. Gry digonl rrows indicte the stimulus trjectories shown s red rrows in nd. Points overlid on ech rrow represent spikes tht occurred, for ech of 5 repetitions, t the corresponding sptil nd temporl positions of the stimulus. Points plotted on other digonls represent the responses to stimuli eginning t other ITDs. (e,f) Contour plots of responses shown in c nd d. Asterisks indicte the est ITD vlue for ech time in. course of the effects of motion on receptive field structure, nd to relte such chnges to ehvior. The sptiotemporl receptive field of single optic tectum unit ws mesured in response to simulted motion t speed of ms ITD per s, or B31 per s (Fig. 1c f; for rn owls,.5 ms ITDE 11, ref. 16). Responses to ech ITD sweep (Fig. 1c,d, digonls) incresed s the stimulus entered the unit s receptive field. The verge responses to ll stimuli ws clculted s function of ITD nd time reltive to sound onset (Fig. 1e,f). Ner sound onset, the receptive field ws reltively rod nd centered on 17 ms ITD with the right er leding (B71 right). Within 1 ms of sound onset, the receptive field hd shrpenedmrkedlynd,y3ms,thereceptivefieldhdshifted towrd more right er leding ITDs for leftwrd motion (Fig. 1e, sterisks) nd towrd more left er leding ITDs for rightwrd motion (Fig. 1f, sterisks). By the lst ms of the stimulus, leftwrd motion hd induced 14 ± 1.5 ms shift (men ± s.e.m.; B61) nd rightwrd motion hd induced 1 ± 1.9 msshift(b51) in the weighted verge of the responses (est ITD; Methods) reltive to the est ITD for the receptive field mesured in response to sttionry stimuli (horizontl lckline).thedynmicllyshiftedestitdsforleftwrdndrightwrd motion, mesured from responses 1, ms fter sound onset, were ech significntly different from the est ITDs mesured for interleved, -ms-long sttionry stimuli (P o.1, two-tiled t-test). The verge receptive field shifts induced cross the entire popultion of smpled sites (n ¼ 17) ws mesured in response to speed of ms ITDpers(B31 per s; Fig. ). The shifts developed rpidly over the first severl hundred milliseconds (exponentil fit, time 4 Leftwrd motion Rightwrd motion 1 Percent of mx. Figure s in sptiotemporl receptive fields in response to stimulus motion for the popultion. (,) Averge responses for ll sites to moving uditory stimuli ( ms ITD per s). Individul receptive fields were normlized nd centered ( ms ITD) reltive to the est ITD mesured with sttionry stimuli (horizontl lines). (c,d) Schemtic illustrtion of the effect of stimulus motion on the distriution of uditory responses cross the neurl mp of spce in the optic tectum. Blck ovls represent the re of optic tectum ctivted y sttionry sound nd red ovls represent the re of optic tectum ctivted y moving sound t the sme loction. Arrows indicte the direction of stimulus motion cross the neurl representtion of spce. c reltive to sound onset (ms) d 144 VOLUME 9 [ NUMBER 11 [ NOVEMBER 6 NATURE NEUROSCIENCE

3 6 Nture Pulishing Group constnt ¼ 6 ms). The mgnitudes of the finl shifts were 7 ± 1 ms (B31) for oth leftwrd nd rightwrd motion (Fig.,, sterisks). For motion of ms ITD per s, est ITD vlues shifted in the predictive direction for every site tested (mesured from 1, ms fter sound onset). The est ITDs to leftwrd motion were significntly different from the est ITDs to rightwrd motion for 14 of the 17 individul sites (mesured from 1, ms fter sound onset; P o.5, two-tiled t-test). For the popultion, est ITDs for rightwrd nd leftwrd motion (mesured from 1, ms fter sound onset) were ech significntly different from the est ITDs mesured for -ms-long sttionry stimuli (P o.1, pired two-tiled t-test). The predictive shifts in receptive fields could e medited y chnge in either of the receptive field orders: the order tht the stimulus pproched first (leding edge) or the order t which the stimulus exited the receptive field (lgging edge). In fct, we found tht oth edges shifted significntly in the predictive direction (Fig. 3; P o.5, two-tiled t-test). Thus, overll receptive field shpe nd the extent of the popultion response in the optic tectum were mintined in response to motion. Becuse spce is represented topogrphiclly in the optic tectum, the popultion receptive field (Fig.,) cn e used to infer the verge distriution of neurl ctivity cross the optic tectum spce mp, s function of time, in response to moving sound. The region of the tectl mp tht responded to sttionry stimuli of given ITD vlue (Fig. c,d, lck ovl) ws different from the region tht responded to moving stimuli of the sme ITD vlue (Fig. c,d, red ovl). The optic tectum encodes gze chnges s topogrphic motor mp tht is ligned with the uditory mp mesured with sttionry stimuli 17. Assuming tht this motor mp remins constnt, the motion-induced shift in uditory responses cross the optic tectum encodes gze chnge to the future loction of moving uditory stimulus. Shift of est , reltive to sound onset (ms) Shift of RF edge (µs ITD) Leding edge Lgging edge reltive to sound onset (ms) 1, Slope of lgging edge (µs ITD per s) Receptive field shifts compenste for sensorimotor delys In order for neuronl ctivity in the optic tectum to predict sound source loction t some future time, the mgnitude of receptive field shifts must increse with stimulus speed. This ws found to e the cse. We defined receptive field shifts s hlf the difference etween the est ITDs for rightwrd nd leftwrd motion (Fig. 4). At sound onset, receptive field shifts lgged ehind the stimulus, s evidenced y the negtive difference etween leftwrd nd rightwrd est ITDs. This lg ws due to the B ms uditory response ltency of the optic tectum units. Leftwrd nd rightwrd est ITDs were identicl (Fig. 4, dshed line) only fter unit tuning hd shifted enough to compenste for response ltency, which hd occurred for ll stimulus speeds y ms fter sound onset. Incresing stimulus speeds cused systemtic increses in the mgnitude of the finl shifts (mesured 1, ms fter sound onset; P o.1, one-wy nlysis of vrince (ANOVA)). The receptive field shifts demonstrted here were of the pproprite direction nd mgnitude to generte dptive ehvior. We clculted the time-led tht corresponded to prticulr receptive field shift y dividing the difference etween the est ITDs mesured for moving nd sttionry stimuli y the speed of the moving stimulus. Predictive time-leds rnged from 7 ms to 144 ms for the speeds tested (Fig. 4). -leds greter thn zero indicte tht the receptive field shifts compensted eyond the sensory response delys. The time-leds mtched the motor delys for the circuit, s sccdic gze Slope of leding edge (µs ITD per s) Figure 3 s of the leding nd lgging edges of the receptive field mesured t ms ITD per s. () Averge shift in the two receptive field edges. At ech time in, edges re defined s the ITD vlue tht genertes 5% of the mximum response of the finl time in. Error rs re ootstrp s.e.m () Shift of leding versus lgging edge during the finl 9 ms of the stimulus (slope of line fit to ech edge s function of time). Positive vlues indicte shifts in the predictive direction. Blck sterisks re the shifts of edges for ll optic tectum sites. The white dot indictes the shift resulting from the computtionl model with the sme prmeters s in Figure 5. Predictive time led (ms) Sound speed (µs ITD per s) Figure 4 Receptive field shifts increse with stimulus velocity. (), verged cross the popultion, s function of time reltive to sound onset, for speeds of 5,, 4 nd ms ITDpers (thicker lines correspond to fster speeds). The predictive shift is defined s one-hlf the difference etween the est ITD vlues mesured with leftwrd versus rightwrd motion. The dshed line indictes no difference in est ITDs, wheres positive vlues indicte predictive shifts of est ITD. () Predictive time-leds for ll speeds tested. The horizontl line t 1 ms indictes the time-led pproprite for orienting movements. The horizontl line t ms indictes the time-lg expected due to the uditory response delys. All points represent the verge predictive shift in est ITD from the lst ms of pnel divided y the stimulus speed. Error rs re ootstrp s.e.m. for oth nd. chnges evoked y electricl microstimultion of the owl s optic tectum re completed in pproximtely 1 ms (ref. 17). Thus, the shifts were lrge enough to compenste for motor s well s sensory delys for ll speeds tested. Our results demonstrte tht the representtion of moving uditory stimulus in the optic tectum shifts dynmiclly, nd compenstes dptively for the direction nd speed of stimulus motion. Immeditely following NATURE NEUROSCIENCE VOLUME 9 [ NUMBER 11 [ NOVEMBER

4 6 Nture Pulishing Group ITD Stimuli Shift of est ITD Sttionry receptive field g Gin function h , reltive to sound onset (ms) Feedck filter Threshold Slope of lgging edge (µs ITD per s) sound onset, stimulus loction is represented reltively rodly in the spce mp. Within 1 ms of sound onset, the representtion shrpens mrkedly nd the motion of the stimulus cuses the representtion to egin shifting in the predictive direction. By 5 ms fter sound onset, the representtion hs ecome centered t loction in the mp tht predicts where the stimulus source will e pproximtely 1 ms lter. Computtionl model simultes receptive field shifts To identify potentil mechnisms tht could ccount for motioninduced dynmic receptive field shifts, we constructed model for computing optic tectum responses tht ws sensitive to stimulus motion (Fig. 5). The model ws sed on similr model for the retin 1. The sensitivity of the model to the direction of stimulus motion ws ccomplished y hving pst responses modify future responses through negtive feedck: strong responses decresed the susequent gin of neurl responses nd wek responses incresed the susequent gin. The gin ws clculted y filtering responses with n exponentil, nd then inputting the filtered responses (h) into gin function (g(h)). The gin function hd negtive slope t the origin, creting n inverse reltionship etween the strength of previous responses nd the gin of responses during the susequent time step. This model replicted the mgnitude, time course nd speed dependence of the receptive field shifts (Fig. 5). c 1 1 Firing rte Responses ITD Motion receptive field 1 1 Slope of leding edge (µs ITD per s) Figure 5 Computtionl model reproduces receptive field shifts. () A model tht ccounts for predictive shifts of uditory tuning curves in response to motion. Moving uditory stimuli were convolved with smple receptive field mesured with sttionry stimuli (sttionry receptive field) nd multiplied y gin fctor (g) to otin response. The gin fctor ws clculted y filtering the responses with n exponentil (feedck filter) nd inputting the filtered response (h) into the gin function. The response ws then thresholded. Finlly, the responses to ll sound sweeps were comined to otin the sptiotemporl receptive field to the moving stimuli (motion receptive field). The horizontl line indictes est ITD for sttionry stimuli. The sterisks indicte est ITDs s function of time for moving stimuli. () Shift in est ITD s function of time reltive to stimulus onset, for the dt (from Fig. 4; thin lines) nd the model (thick lines). Speeds: 5 (green), (lue), 4 (purple) nd (red) ms ITD per s. (t ¼ 5 ms; I ¼.5 mx(r e (x,t)); B ¼ 1 per s; y ¼ ) (c) Shift of leding versus lgging edges, quntified in the sme mnner s in Figure 3, for the computtionl model over wide rnge of prmeter vlues (t ¼ 15 to 35 ms; B ¼ to 7 per s; y ¼ min(f) tomx(f)). Gry dots, feedck with n inhiitory surround (I ¼.5 mx(r e )); lck dots, feedck without n inhiitory surround (I ¼ ); Asterisk, no feedck (B ¼ ). Negtive feedck ws essentil to yield predictive shifts of oth the lgging nd leding edges of the receptive fields. As the sound crossed the excittory receptive field, responses ecme stronger (incresed h), cusing the gin (g) to decrese ecuse of the negtive slope of the gin function (Fig. 5). This decrese in gin resulted in lower firing rte y the time the sound reched the lgging edge, cusing the lgging edge to shift towrd the pproching sound. Such negtive feedck on excittory drive would correspond to response dpttion, for exmple. However, decrese in gin cused y strong responses lso cused the leding edge of the receptive field to shift in the nonpredictive direction (Fig. 5c, lck dots), indicting tht n dditionl element ws needed to fully explin the dt. Adptive shifts in the leding edge were ccomplished y dding n inhiitory surround to the sttionry receptive field. As sound crossed the inhiitory surround nd pproched the excittory receptive field, inhiition suppressed responses (decresed h), therey cusing n increse in the gin g ecuse of the negtive slope of the gin function (Fig. 5). By the time the sound reched the leding edge of the receptive field, the gin ws lrge, therey dvncing the leding edge in the predictive direction. This increse in gin cused y inhiition would correspond to postinhiitory reound, for exmple. By dding n inhiitory surround to the excittory receptive field, we were le to replicte the predictive shifts tht occurred t oth edges (Fig. 5c, gry dots). As expected, neither receptive field edge shifted without feedck (Fig. 5c; sterisk). The model indicted tht negtive feedck is needed to simulte predictive receptive field shifts in the optic tectum: there must e decrese in unit responsiveness following excittion nd n increse in unit responsiveness following inhiition. These mechnisms should lso shpe unit responses to sequentil, sttionry stimuli tht originte from different loctions in unit s receptive field. We exmined this prediction quntittively, nd compred the results with unit responses recorded in the optic tectum. For oth the model nd the dt, we first presented 5-ms-long priming sound either t the receptive field s excittory center (est ITD; Fig. 6,, white rrowheds) or in the inhiitory surround (est ITD + 6 ms; Fig. 6,, lck rrowheds). The second 5-ms-long test stimulus ws presented from loctions tht spnned the receptive field. The model produced decrese in responsiveness to the sttionry test stimulus when it ws presented immeditely fter the excittory priming stimulus (Fig. 6, white circles). Conversely, the model produced n increse in responsiveness to sttionry test stimulus when it ws presented immeditely fter the inhiitory stimulus (Fig. 6, lck circles). The predictions of the model were tested experimentlly t suset of optic tectum sites (n ¼ 19). The experimentl dt followed the predictions of the model: unit responsiveness decresed following n excittory stimulus (Fig. 6, white 144 VOLUME 9 [ NUMBER 11 [ NOVEMBER 6 NATURE NEUROSCIENCE

5 6 Nture Pulishing Group Normlized response Model Test Inhiitory priming No priming Excittory priming Test Figure 6 Effects of n excittory or inhiitory priming stimulus on responses to susequent test stimulus. () Predictions of the model. () Popultion verge for experimentl dt from the optic tectum (n ¼ 19 sites). Both the priming nd the test stimuli were 5-ms-long noise ursts. White rrowheds indicte the ITD of the excittory priming stimulus; lck rrowheds indicte the ITD of the inhiitory priming stimulus. The curves indicte the verge responses during the susequent test stimulus. White circles (J) re responses to stimuli following the excittory priming stimulus; lck circles () re responses to stimuli following the inhiitory priming stimulus. Dshed lines re responses to the test stimulus lone. In nd, responses were normlized y the mximum firing rte in response to the test stimulus lone. In, dt were ligned reltive to the est ITD for ech site (indicted s ms ITD); error rs represent ootstrp s.e.m. circles; two-tiled t-test, P o.1) nd incresed following n inhiitory stimulus (Fig. 6, lck circles; two-tiled t-test, P ¼.4). DISCUSSION Stimulus motion ffects uditory responses in severl neurl circuits. A numer of studies in the inferior colliculus of gerils, guine pigs nd ts hve demonstrted tht neurl response ptterns chnge with stimulus motion nd tht responses to prticulr vlues of uditory sptil cues depend on the recent history of stimultion,3,5,6. Consistent with our conclusions, these effects hve een ttriuted to dpttion nd postinhiitory reound 6,1,19. However, in these studies the effect of motion ws mesured with single stimulus tht swept cross the receptive field. Such stimulus could not ssess the effects of motion on oth receptive field edges t the sme times fter stimulus onset. Therefore, lthough these studies show tht receptive fields chnge in response to motion, the dt could not distinguish etween shrpening nd shifting of the receptive fields. By using stimulus protocol tht mesured the entire receptive field t equivlent times fter stimulus onset, we demonstrted tht uditory receptive fields in the optic tectum spce mp oth shrpen nd shift following the onset of moving stimulus. Thus, this is the first unequivocl demonstrtion tht uditory receptive fields shift predictively in response to stimulus motion. Moreover, detiled knowledge of the function nd functionl orgniztion of the optic tectum llows us to interpret quntittively the dptive vlue of the motion-induced shifts in receptive field loction. Becuse spce is represented topogrphiclly in the optic tectum,we cn infer the effect of stimulus motion on the distriution of neurl ctivity cross the optic tectum from the effects of motion on the receptive fields of single units (Fig. c,d). In ddition, the ehviorl significnce of the distriution of ctivity in the optic tectum is known: the locus of ctivity encodes chnges in gze direction 17.Thesegze chnges re crried out y sccdic movements of the eyes nd hed, t ltencies nd for durtions tht hve een mesured. The motion-induced shifts in receptive field loction scle nerly linerly with velocity cross the entire rnge tested nd, in this mnner, Dt 6 predict the loction of moving sound B1 ms in the future. This is pproximtely the time required for n owl to cquire n uditory trget with its gze 17.Itislikelythtthese predictive receptive field shifts represent shifts occurring, t lest prtilly, t erlier stges in the uditory pthwy, prticulrly in the externl nucleus of the inferior colliculus (ICX) where the uditory mp of spce is creted 1. By the level of the optic tectum, the mtch etween the mgnitude of the receptive field shifts in the optic tectum nd the shifts needed to execute dptive ehvior is remrkle. To llow these receptive field shifts to develop completely, owls would need to listen to moving sound for t lest 5 ms efore progrmming n orienting response to stimulus (Fig. 4). Although owls cn respond with shorter ltencies (o1 ms) to sounds, they often do not, especilly when more thn one stimulus is present in the environment. When n owl does respond to moving sound with ltency of less thn 5 ms, it should underestimte the required compenstion. Our computtionl model indictes tht the responses of optic tectum neurons must e shped y negtive feedck such tht decrese in responsiveness follows excittion nd n increse in responsiveness follows inhiition. These phenomen hve een demonstrted previously in the uditory spce mp of the ICX, which drives uditory responses in the optic tectum 3. ICX neurons dpt strongly fter eing driven y n excittory stimulus 4. The receptive fields of ICX neurons include extensive inhiitory surrounds 5, nd mny ICX units exhiit reound excittion following stimultion of the inhiitory surround. In ddition, we demonstrted directly tht oth kinds of negtive feedck shpe responses in the owl s optic tectum (Fig. 6). The predictive receptive field shifts we oserved would occur in response either to the motion of stimulus reltive to the owl (stimulus motion) or to the motion of the owl reltive to stimulus (self-induced motion). It is unlikely tht owls experience stimulus motion with speeds much ove 11 per s (perpendiculr trnsltion of cm s 1 t distnce of 1 m). While hunting, however, they might experience high speeds of self-induced motion s they fly pst n coustic stimulus tht is offset from the owl s direction of flight. Indeed, the predictive shifts of the optic tectum mp my e prticulrly vlule for mking corrective sccdes to coustic stimuli s the owl pproches its trget. The receptive field shifts oserved in this study er striking resemlnce to motion-induced perceptul effects tht hve een reported in humns for numer of stimulus fetures. For instnce, sound motion shifts our perception of sound loction hed of the true loction of the source 6. Like the receptive field shifts oserved in this study, which develop over severl hundred milliseconds, the perceived loction of moving stimulus is ised more y 3-ms-long sound thn y shorter sound. As with our neurl recordings, the mgnitude of the perceptul effect increses with stimulus velocity. Similr motion-induced perceptul effects hve een oserved for wide vriety of stimulus prmeters, including loction nd frequency in the uditory domin 7, nd luminnce, color nd sptil frequency in the visul domin,9. As demonstrted y our model, motiondependent receptive field shifts cn occur in mpped representtions NATURE NEUROSCIENCE VOLUME 9 [ NUMBER 11 [ NOVEMBER

6 6 Nture Pulishing Group s result of common neurl properties such s dpttion nd reound from lterl inhiition, without the involvement of specilized motion detectors. Therefore, to the degree tht sensory prmeter is processed y neurl circuits tht possess these common properties, the results descried here for the optic tectum indicte tht motion will induce predictive shifts in the representtions of these prmeters throughout the centrl nervous system. METHODS Animls. Twelve dult rn owls were pir-housed in flight viries. Birds were cred for in ccordnce with the US Ntionl Institutes of Helth Guide for the Cre nd Use of Lortory Animls nd the Stnford University Institutionl Animl Cre nd Use Committee. Electrophysiologicl recordings. Owls were nesthetized with 1% hlothne mixed with nitrous oxide nd oxygen (45:55), nd smll stinless steel fstener ws ttched to the rer of the skull with dentl crylic. Crniotomies were opened dorsl to the optic tectum, sed on stereotxic coordintes. During recording sessions, owls were suspended in prone position with the hed stilized using the mounted fstener. Nitrous oxide nd oxygen (45:55) were dministered continuously. Multiunit nd single-unit responses were isolted from the deep lyers (11 13) of the optic tectum with insulted tungsten microelectrodes (6 13 MO t 1 khz). The lyers were identified on the sis of their firing properties, s confirmed previously 3. Using constntly moving serch stimulus, we serched within these lyers for neurons tht exhiited sustined firing to stimuli within their receptive fields. Units were smpled from the portion of the optic tectum tht represented frontl spce (within 1 of the visul xes). A totl of 19, 11, 1 nd 17 single-unit or multiunit sites were mesured for speeds of 5,, 4, nd ms ITD per s, respectively. In ddition, 19 multiunit sites were recorded in tests for dpttion nd postinhiitory reound with sttionry stimuli. Spike times nd wveforms were stored using TDT hrdwre (RA-16) controlled y customized MATLAB (Mthworks) softwre. Stimuli. Auditory responses were ssessed y presenting frozen rodnd noise ursts (flt mplitude spectrum ± 1 db; 1 khz; 3 db ove threshold) dichoticlly through erphones plced 5 mm from the tympnic memrne. The noise wveform presented to ech er ws the sme, except for difference in the reltive timing tht corresponded to the ITD. In this study, negtive ITDs indicte left er leding sounds nd positive ITDs indicte right er leding sounds. For oth sttionry nd moving stimuli, ITDs were generted using the ShortDynDel function running on TDT hrdwre (RP). At every smpled time point, this function interpoltes etween the current nd the previous signl vlue using the function sin(x)/x, nd then shifts the signl y the pproprite dely. Wveforms were smpled t 5 khz. For virtul motion stimuli, ITD chnged t constnt rte for the 1,-ms durtion of the sound (Fig. 1,, rrows). The stimuli were spced 1 ms ITD prt nd trversed ll or prt of the receptive field. The ITD of moving stimuli chnged t speeds of 5,, 4 or ms ITD per s, in order to simulte uditory motion t speeds of,, 16 or 31 per s, respectively. Stimulus sweeps for ll speeds nd oth directions were rndomly interleved nd were presented with 5 repetitions t n interstimulus intervl of s. Spike times nd stimulus positions were recorded throughout ech stimulus presenttion. For mesuring receptive fields to sttionry stimuli, -ms-long noise ursts with constnt ITDs were presented in rndomly interleved fshion, with ITDs spnning 1-ms rnge centered on the site s est ITD. Responses to sttionry noise ursts of 1 ms durtion were lso mesured t suset of sites to generte sttionry receptive field for use in the computtionl model. In tests for dpttion nd postinhiitory reound (Fig. 6), we presented pirs of sttionry, 5-ms-long, noise urst stimuli. A priming stimulus ws delivered immeditely efore test stimulus. The ITD of the priming stimulus ws either t the site s est ITD, to test for dpttion, or t est ITD + 6 ms in the contrlterl direction, to test for postinhiitory reound. The susequent test stimulus mpped out the site s responsiveness cross the ITD tuning curve. Test ITDs were presented in -ms steps in rndom order. Additionlly, the sme test ITDs were presented in the sence of priming stimulus. All stimulus comintions were rndomly interleved, nd ech stimulus ws repeted 15 times. Dt nlysis nd sttistics. To clculte the sptiotemporl receptive fields for sttionry nd moving stimuli, the response to ech stimulus sweep ws divided into evenly spced time ins. We used 1-ms time ins for ll sttisticl nlyses nd figures, with two exceptions. In Figures 1e,f nd,, the first three time ins re 4 ms nd the remining re ms, so tht rpidly occurring chnges in the receptive field cn e seen. Similrly, in Figure 3 the first two time ins re 5 ms, s opposed to 1 ms, so tht rpidly occurring shifts in receptive field edge loction cn e seen. The receptive field ws constructed y plotting the verge firing rte s function of the time in nd the verge stimulus ITD during tht time in (Fig. 1e,f nd Fig.,). Best ITDs were clculted s the weighted verge for ll ITD ins yielding t lest 5% of the mximum firing rte. When clculting the popultion receptive field (Fig.,) for moving stimuli, ech motion receptive field ws centered sed on the est ITD for sttionry stimuli nd normlized y dividing the entire receptive field mtrix y its mximum vlue. Then, the centered nd normlized receptive fields were verged cross the popultion of recording sites. All sttisticl tests for motion-dependent shifts of the est ITD were performed on the est ITDs from the finl ms ( 1, ms poststimulus onset for moving stimuli). This time in ws chosen ecuse predictive receptive field shifts hd stilized y this point. For the smple site of Figure 1, two-tiled t-tests were performed to determine whether the est ITDs for leftwrd nd rightwrd moving stimuli were different from the est ITD mesured with sttionry stimuli, from ms fter stimulus onset. Additionlly, t ech site, two-tiled t-test ws performed to determine whether the est ITDs for leftwrd nd rightwrd motion were different. Finlly, for the popultion, pired two-tiled t-tests determined whether the est ITDs for leftwrd nd rightwrd moving stimuli were different from est ITDs mesured with sttionry stimuli. To clculte the velocity dependence of the shift in ITD tuning (Fig. 4), the est ITD ws clculted for ech 1-ms time in. For given site nd given velocity of motion, the verge predictive shift ws defined s the est ITD for leftwrd motion sutrcted from the est ITD for rightwrd motion, divided y. For ech velocity, the predictive shifts for ll sites were verged cross the popultion to crete Figure 4. To test whether stimulus velocity ws significnt fctor in determining the mount of receptive field shift, one-wy ANOVA ws performed on the men predictive shift (sed on est ITDs mesured 1, ms fter stimulus onset) for ech speed tested. The leding nd lgging receptive field edges for ech time in were defined s the ITD vlues tht corresponded to firing rte tht ws 5% of the mximum firing rte for the finl time in. In contrst to the previous nlyses, to test for shift in the edges, the first 1 ms were excluded ecuse of the mrked receptive field shrpening tht occurred in this erly time period (Fig. 1). A line ws fit to the leding nd lgging edges, respectively, s function of time for ech site, using liner regression. Two-tiled t-tests were performed on the slopes of the fitted lines to determine whether they were significntly different from zero. We pplied two-tiled t-tests to determine the significnce of chnges in responses to the sttionry test stimulus following the excittory or inhiitory priming stimulus (Fig. 6). For ech kind of priming stimulus, we compred responses to the test stimulus t the est ITD with nd without the priming stimulus. Model. The model, which ws used to predict responses to moving sounds, consisted of two min components. The first ws the receptive field in response to sttionry sounds. The second ws negtive feedck component, which cused strong previous responses to decrese the gin of future responses nd wek previous responses to increse the gin of future responses. The sttionry receptive field, R(x,t), ws creted y summing n excittory nd n inhiitory component tht is, R(x,t) ¼ R e (x,t) +R i (x,t). R e (x,t), the excittory component of the sttionry receptive field, ws otined y 1444 VOLUME 9 [ NUMBER 11 [ NOVEMBER 6 NATURE NEUROSCIENCE

7 6 Nture Pulishing Group mesuring the responses of representtive optic tectum unit to very short (1 ms) sound ursts tht rnged in ITD, centered on the unit s est ITD. The excittory field egn ms fter sound onset, corresponding to the ltency of the unit. R i (x,t), the inhiitory receptive field, ws sptilly uniform in strength nd egn 1 ms fter stimulus onset. The reltive timing of excittion nd inhiition ws chosen to e consistent with previous reports in the rn owl uditory spce mp. The strength of the inhiitory field ws determined y I, free prmeter in the model. The rod extent of the inhiitory field reflected the inhiitory surrounds of uditory receptive fields tht hve een reported in the uditory spce mp 5. The prmeters of the inhiitory field were the following: t 1 ms R i ðx; tþ ¼ I 1 msoto5 ms To model the response, f(t), to sweep of the sound, the moving stimulus, S(x,t), ws convolved with the sttionry receptive field, R(x,t), nd multiplied y gin function, g(h). Z 1 f ðtþ ¼gðhÞ 1 Z t dx 1 dt Rðx;t t ÞSðx;t Þ The gin function s input, h, ws derived y filtering the response with n exponentil ( feedck filter in Fig. 5), with time constnt t nd mgnitude B s free prmeters. hðtþ ¼ Z t 1 f ðt ÞBe ðt t Þ=t dt The gin function, g(h), rnged from to, nd hd negtive slope t the origin, in order to crete negtive feedck. As the precise form of the negtive feedck term in the optic tectum is unknown, we chose piecewise liner function for simplicity. < gðhþ ¼ h=5+1 : h 5 5oh 5 h45 Finlly, the responses were thresholded. The threshold, y, wsthefinlfree prmeter in the model. Tð f Þ¼ y f y f f4y To plot the sptiotemporl receptive field to moving sounds, multiple ITD sweeps were used to spn the receptive field. Responses to the individul sweeps were comined using the sme pproch tht ws used for the experimentl dt. The four free prmeters in Figure 5 were chosen to minimize the verge differences in the est ITD vlues etween the dt nd the model cross the four speeds. ACKNOWLEDGMENTS We thnk S. Bccus, R. Aldrich, A. Keuroghlin, D. Winkowski nd K. Mczko for helpful comments on this pper, nd P. Knudsen for technicl ssistnce. I.B.W. nd J.F.B. re recipients of Ntionl Science Foundtion grdute reserch fellowships. J.F.B. is recipient of Ntionl Reserch Service Awrd. Support for the experiments cme from the US Ntionl Institutes of Helth. AUTHOR CONTRIBUTIONS E.I.K., J.F.B. nd I.B.W. conceived the experiments nd wrote the pper. J.F.B. nd I.B.W. performed the experiments. J.F.B. performed the dt nlysis nd sttistics. I.B.W. developed the computtionl model. COMPETING INTERESTS STATEMENT The uthors declre tht they hve no competing finncil interests. Pulished online t Reprints nd permissions informtion is ville online t reprintsndpermissions/ 1. Berry, M.J., II, Brivnlou, I.H., Jordn, T.A. & Meister, M. Anticiption of moving stimuli y the retin. Nture 39, (1999).. Inghm, N.J., Hrt, H.C. & McAlpine, D. 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Multiple sites of dptive plsticity in the owl s uditory locliztion pthwy. J. Neurosci. 4, (4). NATURE NEUROSCIENCE VOLUME 9 [ NUMBER 11 [ NOVEMBER