Publications

Shadron K, Peña JL (2023) Development of frequency tuning shaped by spatial cue reliability in the barn owl's auditory midbrain. eLife, 12:e84760, Pubmed

Ferger R, Shadron K, Fischer BJ, Peña JL (2021) Barn owl's auditory space map activity matching conditions for a population vector readout to drive adaptive sound-localization behavior. Journal of Neuroscience, 41(50): 10305-10315. Pubmed

Gorman JC, Tufte OL, Miller AVR, DeBello WM, Peña JL, Fischer BJ (2021) Diverse processing underlying frequency integration in midbrain neurons of barn owls. PLoS Computational Biology, 17(11):e1009569. Pubmed

Pavao R, Sussman ES, Fischer BJ, Pena JL (2020) Natural ITD statistics predict human auditory spatial perception eLife, 9:e51927.

Beckert MV, Fischer BJ, Pena JL (2020) Effect of stimulus-dependent spike timing on population coding of sound location in the owl’s auditory midbrain. eNeuro, 7(2) ENEURO.0244-19.2020 1–21.

Pena JL, Cazettes F, Beckert MV, Fischer BJ (2019) Viewpoint: Synthesis of hemispheric ITD tuning from the readout of a neural map: commonalities of proposed coding schemes in birds and mammals. Journal of Neuroscience, 39: 9053-9061.

Fischer BJ, Wydick JL, Köppl C, Pena JL (2018) Multidimensional stimulus encoding in the auditory nerve of the barn owl. J. Acoustical Society of America, in press.

Cazettes F, Fischer BJ, Beckert MV, Pena JL (2018) Emergence of an adaptive command for orienting behavior in premotor brainstem neurons of barn owls. Journal of Neuroscience, 38: 7270-7279. Pubmed

This research shows how statistics of the sensory input can be integrated into a behavioral command by readout of a sensory representation. The firing rate of midbrain premotor neurons receiving sensory information from a topographic representation of auditory space is weighted by the reliability of sensory cues. We show that these premotor responses are consistent with a weighted convergence from the topographic sensory representation. This convergence was also tested behaviorally, where manipulation of stimulus properties led to bidirectional changes in sound localization errors. Thus a topographic representation of auditory space is translated into a premotor command for sound localization that is modulated by sensory reliability.

Batista G, Johnson JL, Dominguez E, Costa-Mattioli M, Pena JL (2018) Regulation of filial imprinting and structural plasticity by mTORC1 in newborn chickens. Scientific Reports, 8:8044 | DOI:10.1038/s41598-018-26479-1. Pubmed

Dysregulation of the mechanistic target of rapamycin complex 1 (mTORC1) signaling leads to memory deficits and abnormal social behaviors in adults. However, whether mTORC1 is involved in critical periods of early learning remains largely unexplored. Our study addressed this question by investigating imprinting, a form of learning constrained to a sensitive period that supports filial attachment, in newborn chickens. Imprinting to virtual objects and sounds was assessed after acute manipulations of mTORC1. To further understand the role of mTORC1 during the critical period, structural plasticity was analyzed using DiOlistic labeling of dendritic spines. We found that mTORC1 is required for the emergence of experience-dependent preferences and structural plasticity within brain regions controlling behavior. Furthermore, upon critical period closure, pharmacological activation of the AKT/mTORC1 pathway was sufficient to rescue imprinting across sensory modalities. Thus, our results uncover a novel role of mTORC1 in the formation of imprinted memories and experience-dependent reorganization of neural circuits during a critical period.

Beckert MV, Pavao R, Pena JL (2017) Distinct correlation structure supporting a rate-code for sound localization in the owl's auditory forebrain. eNeuro, https://doi.org/10.1523/ENEURO.0144-17.2017. Pubmed

Despite their established involvement in sound localization, our understanding of how the midbrain and forebrain encode sound location is limited. An outstanding difference between these regions is the lack of obvious topographic representations of auditory space in the forebrain. To shed light on the circuit function, we examined the tuning and correlation structure in responses of nearby neurons in the midbrain and forebrain. Interestingly, a different correlation structure emerged in the forebrain: uniform tuning shape and uncorrelated response variability. This finding highlights differences between the midbrain and forebrain representation of auditory space and provides evidence supporting a rate code for sound location in the forebrain.

Wasmuht DF, Pena JL, Gutfreund Y (2017) Stimulus-specific adaptation to visual but not auditory motion direction in the barn owl’s optic tectum. European Journal of Neuroscience, 45: 610–621. Pubmed

Whether the auditory and visual systems use a similar coding strategy to represent motion direction is an open question. We investigated this question in the barn owl's optic tectum (OT) testing stimulus‐specific adaptation (SSA) to the direction of motion. SSA, the reduction of the response to a repetitive stimulus that does not generalize to other stimuli, has been well established in OT neurons. SSA suggests a separate representation of the adapted stimulus in upstream pathways. So far, only SSA to static stimuli has been studied in the OT. Here, we examined adaptation to moving auditory and visual stimuli. SSA to motion direction was examined using repeated presentations of moving stimuli, occasionally switching motion to the opposite direction. Acoustic motion was either mimicked by varying binaural spatial cues or implemented in free field using a speaker array. While OT neurons displayed SSA to motion direction in visual space, neither stimulation paradigms elicited significant SSA to auditory motion direction. These findings show a qualitative difference in how auditory and visual motion is processed in the OT and support the existence of dedicated circuitry for representing motion direction in the early stages of visual but not the auditory system.

Batista G, Johnson JL, Dominguez E, Costa-Mattioli M, Pena JL (2016) Translational control of auditory imprinting and structural plasticity by eIF2a. eLife, 10.7554/eLife.17197.001 Pubmed

The formation of imprinted memories during a critical period is crucial for vital behaviors, including filial attachment. Yet, little is known about the underlying molecular mechanisms. Using a combination of behavior, pharmacology, in vivo surface sensing of translation (SUnSET) and DiOlistic labeling we found that, translational control by the eukaryotic translation initiation factor 2 alpha (eIF2α) bidirectionally regulates auditory but not visual imprinting and related changes in structural plasticity in chickens. Increasing phosphorylation of eIF2α (p-eIF2α) reduces translation rates and spine plasticity, and selectively impairs auditory imprinting. By contrast, inhibition of an eIF2α kinase or blocking the translational program controlled by p-eIF2α enhances auditory imprinting. Importantly, these manipulations are able to reopen the critical period. Thus, we have identified a translational control mechanism that selectively underlies auditory imprinting. Restoring translational control of eIF2α holds the promise to rejuvenate adult brain plasticity and restore learning and memory in a variety of cognitive disorders.

Carr CE, Pena JL (2016) Cracking an improbable sensory map. J Exp Biol. 219(Pt 24):3829-3831. Pubmed

Catherine E. Carr and Jose L. Peña discuss the impact of a series of classic papers presenting the discovery of the owl auditory map published by Mark Konishi and Eric Knudsen in the 1970s.

Fischer BJ, Pena JL (2016) Optimal nonlinear cue integration for sound localization. Journal of Computational Neuroscience. DOI 10.1007/s10827-016-0626-4 Pubmed

Integration of multiple sensory cues can improve performance in detection and estimation tasks. There is an open theoretical question of the conditions under which linear or nonlinear cue combination is Bayes-optimal. We demonstrate that a neural population decoded by a population vector requires nonlinear cue combination to approximate Bayesian inference. Specifically, if cues are conditionally independent, multiplicative cue combination is optimal for the population vector. The model was tested on neural and behavioral responses in the barn owl's sound localization system where space-specific neurons owe their selectivity to multiplicative tuning to sound localization cues interaural phase (IPD) and level (ILD) differences. We found that IPD and ILD cues are approximately conditionally independent. As a result, the multiplicative combination selectivity to IPD and ILD of midbrain space-specific neurons permits a population vector to perform Bayesian cue combination. We further show that this model describes the owl's localization behavior in azimuth and elevation. This work provides theoretical justification and experimental evidence supporting the optimality of nonlinear cue combination.

Cazettes F, Fischer BJ, Peña JL (2016) Cue reliability represented in the shape of tuning curves in the owl's sound localization system. The Journal of Neuroscience, 36:2101-2110. Pubmed

In natural environments, sensory cues are often corrupted by noise and are therefore unreliable. To make the best decisions, the brain must estimate the degree to which a cue can be trusted. The behaviorally relevant neural correlates of cue reliability are debated. In this study, we used the barn owl's sound localization system to address this question. We demonstrated that the mechanisms that account for spatial selectivity also explained how neural responses changed with degraded signals. This allowed for the neurons' selectivity to capture cue reliability, influencing the population readout commanding the owl's sound-orienting behavior.

Rich D, Cazettes F, Wang Y, Pena JL, Fischer BJ (2015) Neural representation of probabilities for Bayesian inference. Journal of Computational Neuroscience, 10.1007/s10827-014-0545-1. Link

This paper tested different schemes for how the brain could represent probabilities on owl’s auditory neurons: a population code where the stimulus-driven activity and distribution of preferred stimuli in the population represent a likelihood function and a prior; the sampling hypothesis which proposes that the stimulus-driven activity over time represents a posterior probability and that the spontaneous activity represents a prior; and the class of models which propose that a population of neurons represents a posterior probability in a distributed code. The spontaneous firing rate and the average stimulus-driven response were not consistent with predictions of the sampling hypothesis. In addition, neural activity under varying levels of sensory noise did not reflect a posterior probability. Thus responses were only consistent with the non-uniform population code model.

Cazettes F, Fischer BJ, Peña JL (2014) Spatial cue reliability drives frequency tuning in the Barn Owl's midbrain. eLife, 2014;10.7554/eLife.04854. Pubmed

The study used the filtering properties of the owl's head to predict the reliability of the timing cue used to localize sounds in noisy environments. For each direction, there was a frequency range that carried the most reliable cues. The study then showed a remarkable correlation between the frequencies preferred by space-specific neurons and the range that carried the most reliable cue for each direction. This paper is strong evidence indicating that the brain is sensitive to statistics of sensory cues related to the degree of uncertainty of the sensory input.

Fontaine B, Köppl C, Pena JL (2014) Reverse correlation analysis of auditory-nerve fiber response to broadband noise in bird, the Barn owl. Journal of the Association for Research in Otolaryngology, 10.1007/s10162-014-0494-4. Pubmed

While the barn owl has been extensively used as a model for sound localization and temporal coding, less is known about the mechanisms at its sensory organ, the basilar papilla (homologous to the mammalian cochlea). This paper characterized, for the first time in the avian system, the auditory nerve fiber responses to broadband noise using reverse correlation. The study showed that complex features such as the dependence of phase on input level, can still be consistent with simple linear filtering. This paper allows examining hypotheses put forward for mammalian cochlea.

Fontaine B, McLeod KM, Lubejko ST, Steinberg LJ, Köppl C, Pena JL (2014) Emergence of band-pass filtering through adaptive spiking in the owl's cochlear nucleus. Journal of Neurophysiology, 112: 430-445. Pubmed

Ascending the auditory pathway, neurons increasingly show a preference for envelope modulation frequencies. This study targeted a transition between auditory nerve fibers and the cochlear nucleus. The paper linked spike threshold adaptation in cochlear-nucleus neurons to their selectivity to modulation frequencies. Thus a basic mechanism such as spike threshold adaptation could explain the enhanced efficiency of envelope coding from the auditory nerve to the cochlear nucleus.

Fontaine B, Pena JL, Brette R (2014) Spike-threshold adaptation predicted by membrane potential dynamics in vivo. PLoS Computational Biology, 10: e1003560. Pubmed

Space specific neurons in the owl’s inferior colliculus are selective for motion direction. We found that preference for sounds moving toward frontal space increased with eccentricity in spatial tuning. This distribution was consistent with larger receptive-field asymmetry in neurons tuned to more peripheral auditory space. Directions that elicited larger response induced stronger forward suppression on the response at subsequent locations along the sound’s trajectory, thus making the response direction selective. The paper concluded that response adaptation and receptive-field shape could explain direction selectivity to acoustic motion and an orderly distribution of preferred direction.

Wang Y, Pena JL (2013) Direction selectivity mediated by adaptation in the owl's inferior colliculus. J. Neurosci. 33(49):19167-75. Pubmed

Space specific neurons in the owl’s inferior colliculus are selective for motion direction. We found that preference for sounds moving toward frontal space increased with eccentricity in spatial tuning. This distribution was consistent with larger receptive-field asymmetry in neurons tuned to more peripheral auditory space. Directions that elicited larger response induced stronger forward suppression on the response at subsequent locations along the sound’s trajectory, thus making the response direction selective. The paper concluded that response adaptation and receptive-field shape could explain direction selectivity to acoustic motion and an orderly distribution of preferred direction.

Steinberg LJ, Fischer BJ, Pena JL (2013) Binaural gain modulation of spectrotemporal tuning in the ILD coding pathway. J. Neurosci. 33:11089–11099. Pubmed

Interaural level difference (ILD) is a critical cue for sound localization. ILD-detector neurons in the owl’s lateral lemniscus (LLDp), equivalent to the mammalian LSO, receive excitatory input from one side and inhibitory from the other. Here we examined the spectrotemporal tuning of both type of inputs and how they converge. We found that the firing of LLDp neurons is highly locked to the stimulus envelope. The inhibitory input, acting as a gain modulator, enhances the reliability of envelope coding in LLDp.

Wang Y, Shanbhag SJ, Fischer BJ, Peña JL (2012) Population-wide bias of surround suppression in auditory spatial receptive fields of the owl's midbrain. J Neurosci. 32(31):10470-8. Pubmed

The owl’s midbrain contains a map of auditory space where the front is overrepresented. This paper reports a population-wide bias in the receptive fields of the neurons that constitute the map, such that lateral suppression from frontal space was always stronger. The findings could be predicted by a population of neurons with preferred directions overrepresenting frontal space and exerting lateral inhibition on each other. Thus, the uneven distribution of spatial tuning explained the topography of an emergent tuning property.

Fischer BJ, Steinberg LJ, Fontaine B, Brette R, Peña JL (2011) Effect of instantaneous frequency glides on interaural time difference processing by auditory coincidence detectors. Proc Natl Acad Sci USA 108(44):18138-43. Pubmed

Here we investigated the spectrotemporal selectivity of monaural inputs in neurons that detect interaural time difference (ITD). We found that these inputs are matched not just for frequency but for frequency over time. A model based on cross-correlation showed that ITD tuning depends strongly on this selectivity. We further showed that this refinement could develop through spike timing-dependent plasticity. This paper offered an alternative to how ITD tuning could be regulated.

Steinberg LJ, Peña JL (2011) Difference in response reliability predicted by spectrotemporal tuning in the cochlear nuclei of barn owls. J Neurosci. 31(9):3234-42. Pubmed

This study initiated a bottom-up approach to how the auditory system encodes stimulus identity. Envelope coding was compared in the two cochlear nuclei of the barn owl, nucleus angularis (NA) and nucleus magnocellularis (NM). We found that NA neurons, although unable to accurately encode stimulus phase, lock more strongly to the stimulus envelope than NM units. Further, we could relate the shape of the spectrotemporal receptive fields to this enhanced tuning. These findings suggest a dichotomy in envelope coding as early as at the first stage in the central auditory pathway.

Fischer BJ, Peña JL (2011) Owl's behavior and neural representation predicted by Bayesian inference. Nat Neurosci. 14(8):1061-6. Pubmed

Owls systematically underestimate peripheral source directions. This paper reports that this behavior is predicted by a Bayesian model that emphasizes central directions. It is proposed that a bias in the neural coding of auditory space achieves high behavioral accuracy in the front at the cost of inducing errors in the periphery. This bias was consistent with the overrepresentation of frontal space observed in the map. This paper also reports that the properties of the map and its neurons allow for a simple population vector to approximate Bayesian inference.

Penzo MA, Peña JL (2011) Depolarization-induced suppression of spontaneous release in the avian midbrain. J Neurosci. 31(10):3602-9. Pubmed

This study focused on the modulation of spontaneous neurotransmitter release by retrograde messengers in the chicken midbrain. Spontaneous neurotransmitter release has been considered synaptic ‘noise’. Recent work, however, suggested that these events could contribute to synaptic function. We found that somatic depolarization suppressed spontaneous synaptic release onto chicken midbrain neurons. These results indicated that these cells can specifically modulate spontaneous neurotransmitter release of its afferent inputs in a retrograde manner.

Fischer BJ, Anderson CH, Peña JL (2009) Multiplicative auditory spatial receptive fields created by a hierarchy of population codes. PLoS One. 4(11):e8015. Pubmed

We built a model that accounted for the emergence of spatial tuning in the owl’s midbrain. The model combined spatial cues nonlinearly but linearly across frequency, as suggested by our intracellular studies. This model provided two advances: First, it embraced the diversity of spiking responses demonstrated experimentally; second, it reconciled multiplicative responses of spatial cues with the presence of linear frequency integration.

Pérez ML, Shanbhag SJ, Peña JL (2009) Auditory spatial tuning at the crossroads of the midbrain and forebrain. J Neurophysiol. 102(3):1472-82. Pubmed

This paper compared the spatial tuning in the midbrain and the auditory thalamus. Thalamic cells respond to a broader frequency range and their tuning to binaural cues varies more across frequency than in the midbrain. The frequency dependence was enhanced by the response to lower frequencies in the thalamus. Despite these differences, neurons in the thalamus could display spatial receptive fields as selective as in the midbrain, suggesting that spatial coding undergoes a change at the entryway to the forebrain.

Penzo MA, Peña JL (2009) Endocannabinoid-mediated long-term depression in the avian midbrain expressed presynaptically and postsynaptically. J Neurosci. 29(13):4131-9. Pubmed

An in vitro preparation of the chicken midbrain was developed to study synaptic plasticity in the avian auditory midbrain. We recorded neurons in the external part of the auditory torus (EX). We studied the connection between EX cells and inputs originating in the midbrain. Repetitive stimulation of these inputs induced LTD, a single-cell process mediated by endocannabinoids. Endocannabinoids both decreased release probability and reduced postsynaptic NMDA-receptor currents. This was the first report of eCB-dependent LTD in the auditory midbrain.

Wild JM, Kubke MF, Peña JL (2008) A pathway for predation in the brain of the barn owl (Tyto alba): projections of the gracile nucleus to the "claw area" of the rostral wulst via the dorsal thalamus. J. Comp. Neurol. 509:156-66. Pubmed

With our colleagues from Auckland, New Zealand, we visited the owl’s somatosensory system. The Wulst of birds, is largely visual, but a relatively small rostral portion contains a representation of the contralateral claw. We investigated whether the input to this “claw area” arises from dorsal thalamic neurons that, in turn, receive their somatosensory input from the gracile nucleus. Using retrograde and anterograde tracers we found a trisynaptic pathway from the body periphery to the telencephalic Wulst, via the dorsal thalamus. This pathway is likely involved in the barn owl’s predatory behavior.

Fischer BJ, Christianson GB, Peña JL (2008) Cross-correlation in the auditory coincidence detectors of owls. J Neurosci. 28(32):8107-15. Pubmed

Interaural time difference (ITD) plays a central role in sound localization. Theory predicts that neurons that detect ITD behave as cross-correlators.  While cross-correlation-like properties have been reported, attempts to show that the shape of the ITD response function is determined by the spectral tuning of these neurons, a core prediction of cross-correlation, have been unsuccessful. The paper demonstrates this relationship in neurons of the owl’s nucleus laminaris, using reverse correlation to estimate the inputs from each side.

Christianson GB, Peña JL (2007) Preservation of spectrotemporal tuning between the nucleus laminaris and the inferior colliculus of the barn owl. J Neurophysiol. 97(5):3544-53. Pubmed

Neurons in the initial stages of the owl’s auditory pathway phase lock to frequencies ass high as 8 kHz. However, phase locking is rapidly abolished in a single-step transition. This paper reports that despite two stages of convergence and loss of phase information, the pathway preserves spectrotemporal information in envelope-locked responses. It is also evidence of simultaneous rate- and timing-based coding strategies representing multiple stimulus parameters.

Christianson GB, Peña JL (2006) Noise reduction of coincidence detector output by the inferior colliculus of the barn owl. J Neurosci. 26(22):5948-54. Pubmed

This article showed that the brainstem of the barn owl realizes a processing analogous to averaging. It showed that the signal-to-noise ratio in encoding of the interaural time difference (ITD) abruptly increases from the place where it is computed to the inferior colliculus (IC). The rate-ITD functions of IC neurons require as little as a single stimulus presentation to show coherent tuning. Average-like processes have been predicted by models of sound localization to remove noise. These data support those predictions and address a recurrent them in theoretical neuroscience.

Peña JL, Konishi M (2004) Robustness of multiplicative processes in auditory spatial tuning. J Neurosci. 24: 8907-8910. Pubmed

Here we tested if neural multiplication was tolerant to changes in the amplitude of one input, as a mathematical multiplication should be. For this, we changed the correlation of sound between the ears, which modulates the amplitude of one of the two independent inputs to these cells. We found that the multiplication remained, as predicted by the mathematical operation.

Peña JL, Konishi M (2002) From postsynaptic potentials to spikes in the genesis of auditory spatial receptive fields. J Neurosci. 22: 5652-5658. Pubmed

Comparison of subthreshold postsynaptic potentials and spiking output of space-specific neurons recorded intracellularly in vivo showed that subthreshold receptive fields were much larger than those measured in spikes. The main cause of these changes was the strategic location of the spiking threshold. In addition, the thresholds of the spikes at the beginning of a sound were lower than those of later sound-induced spikes and of spontaneous spikes due to dependence between the spiking threshold and the preceding change in membrane potential. This phenomenon could account for the sharpening of ITD selectivity from the beginning to end of the stimulus.

Peña JL, Konishi M (2001) Auditory spatial receptive fields created by multiplication. Science. 292(5515):249-52. Pubmed

The space-specific neurons of the owl showed one of the cleanest examples of multiplication by systems of neurons. Multiplication is a powerful processing tool that, if implemented by the brain, would explain the emergence of neural combination selectivity. The owl’s auditory system computes interaural time (ITD) and level (ILD) differences to create a two dimensional map of auditory space. A multiplication of separate inputs tuned to ITD and ILD could account for the response of these neurons to ITD-ILD pairs. This finding lent support not just to models of sound localization but also to the use of multiplication to describe combination selectivity by neurons.

Peña JL, Viete S, Funabiki K, Saberi K, Konishi M (2001) Cochlear and neural delays for coincidence detection in owls. J Neurosci. 21: 9455-9459. Pubmed

This paper tested predictions of two alternative models of ITD detection: one that takes into consideration differences in wave propagation along the cochlear basilar membrane (“stereausis theory”) and another one that uses neural delays (“Jeffress model”). We showed that for the owl there is no need to invoke mechanisms other than neural delays to explain the detection of ITD.

Peña JL, Konishi M (2000) Cellular mechanisms for resolving phase ambiguity in the owl's inferior colliculus. Proc. Nat. Acad. Sci. USA 97: 11787-11792. Pubmed

Here we reported intracellular in vivo recordings in the owl’s inferior colliculus for the first time. We studied how frequencies converge onto these cells to resolve the ambiguity inherent to the periodic nature of sound. The paper reports a largely sublinear integration across frequency and a central role of spiking threshold in disambiguating the response.