José Luis Peña

Owl's behavior and neural representation predicted by Bayesian inference

The owl captures prey using sound localization. In the classical model, the owl infers sound direction from the position of greatest activity in a brain map of auditory space. However, this model fails to describe the actual behavior. Although owls accurately localize sources near the center of gaze, they systematically underestimate peripheral source directions. We found that this behavior is predicted by statistical inference, formulated as a Bayesian model that emphasizes central directions. We propose that there is a bias in the neural coding of auditory space, which, at the expense of inducing errors in the periphery, achieves high behavioral accuracy at the ethologically relevant range. We found that the owls map of auditory space decoded by a population vector is consistent with the behavioral model. Thus, a probabilistic model describes both how the map of auditory space supports behavior and why this representation is optimal.

Spike-Threshold Adaptation Predicted by Membrane Potential Dynamics In Vivo

Neurons encode information in sequences of spikes, which are triggered when their membrane potential crosses a threshold. In vivo, the spiking threshold displays large variability suggesting that threshold dynamics have a profound influence on how the combined input of a neuron is encoded in the spiking. Threshold variability could be explained by adaptation to the membrane potential. However, it could also be the case that most threshold variability reflects noise and processes other than threshold adaptation. Here, we investigated threshold variation in auditory neurons responses recorded in vivo in barn owls. We found that spike threshold is quantitatively predicted by a model in which the threshold adapts, tracking the membrane potential at a short timescale. As a result, in these neurons, slow voltage fluctuations do not contribute to spiking because they are filtered by threshold adaptation. More importantly, these neurons can only respond to input spikes arriving together on a millisecond timescale. These results demonstrate that fast adaptation to the membrane potential captures spike threshold variability in vivo.

Cross-Correlation in the Auditory Coincidence Detectors of Owls

Interaural time difference (ITD) plays a central role in many auditory functions, most importantly in sound localization. The classic model for how ITD is computed was put forth by Jeffress (1948). One of the predictions of the Jeffress model is that the neurons that compute ITD should behave as cross-correlators. Whereas cross-correlation-like properties of the ITD-computing neurons have been reported, attempts to show that the shape of the ITD response function is determined by the spectral tuning of the neuron, a core prediction of cross-correlation, have been unsuccessful. Using reverse correlation analysis, we demonstrate in the barn owl that the relationship between the spectral tuning and the ITD response of the ITD-computing neurons is that predicted by cross-correlation. Moreover, we show that a model of coincidence detector responses derived from responses to binaurally uncorrelated noise is consistent with binaural interaction based on cross-correlation. These results are thus consistent with one of the key tenets of the Jeffress model. Our work sets forth both the methodology to answer whether cross-correlation describes coincidence detector responses and a demonstration that in the barn owl, the result is that expected by theory.

Noise Reduction of Coincidence Detector Output by the Inferior Colliculus of the Barn Owl

A recurring theme in theoretical work is that integration over populations of similarly tuned neurons can reduce neural noise. However, there are relatively few demonstrations of an explicit noise reduction mechanism in a neural network. Here we demonstrate that the brainstem of the barn owl includes a stage of processing apparently devoted to increasing the signal-to-noise ratio in the encoding of the interaural time difference (ITD), one of two primary binaural cues used to compute the position of a sound source in space. In the barn owl, the ITD is processed in a dedicated neural pathway that terminates at the core of the inferior colliculus (ICcc). The actual locus of the computation of the ITD is before ICcc in the nucleus laminaris (NL), and ICcc receives no inputs carrying information that did not originate in NL. Unlike in NL, the rate-ITD functions of ICcc neurons require as little as a single stimulus presentation per ITD to show coherent ITD tuning. ICcc neurons also displayed a greater dynamic range with a maximal difference in ITD response rates approximately double that seen in NL. These results indicate that ICcc neurons perform a computation functionally analogous to averaging across a population of similarly tuned NL neurons.

Structure and function of neonatal social communication in a genetic mouse model of autism

A critical step toward understanding autism spectrum disorder (ASD) is to identify both genetic and environmental risk factors. A number of rare copy number variants (CNVs) have emerged as robust genetic risk factors for ASD, but not all CNV carriers exhibit ASD and the severity of ASD symptoms varies among CNV carriers. Although evidence exists that various environmental factors modulate symptomatic severity, the precise mechanisms by which these factors determine the ultimate severity of ASD are still poorly understood. Here, using a mouse heterozygous for Tbx1 (a gene encoded in 22q11.2 CNV), we demonstrate that a genetically triggered neonatal phenotype in vocalization generates a negative environmental loop in pup–mother social communication. Wild-type pups used individually diverse sequences of simple and complicated call types, but heterozygous pups used individually invariable call sequences with less complicated call types. When played back, representative wild-type call sequences elicited maternal approach, but heterozygous call sequences were ineffective. When the representative wild-type call sequences were randomized, they were ineffective in eliciting vigorous maternal approach behavior. These data demonstrate that an ASD risk gene alters the neonatal call sequence of its carriers and this pup phenotype in turn diminishes maternal care through atypical social communication. Thus, an ASD risk gene induces, through atypical neonatal call sequences, less than optimal maternal care as a negative neonatal environmental factor.

Endocannabinoid-Mediated Long-Term Depression in the Avian Midbrain Expressed Presynaptically and Postsynaptically

Here, we examined long-term synaptic plasticity in the avian auditory midbrain, a region involved in experience-dependent learning. We found that coactivation of N-methyl-d-aspartate receptors (NMDAR) and type 1 cannabinoid receptors (CB1R) induces long-term depression (LTD) at the synapse between the central shell and the external portion of the inferior colliculus of the chicken. Although endocannabinoids are commonly thought of as presynaptic modulators, recent reports have suggested that they can also modulate the postsynaptic site. In the avian midbrain, we found that LTD is mediated by both presynaptic and postsynaptic changes. The presynaptic mechanism consists of a decrease in neurotransmitter release, whereas a depression of NMDAR-mediated current takes place on the postsynaptic side. Both the presynaptic and the postsynaptic effects depend on CB1R activation. The reduction of postsynaptic NMDAR currents represents a novel role of endocannabinoids in synaptic modulation.

Robustness of Multiplicative Processes in Auditory Spatial Tuning

Auditory space-specific neurons in the owls inferior colliculus selectively respond to the direction of sound propagation, which is defined by combinations of interaural time (ITD) and level (ILD) differences. Mathematical analyses show that the amplitude of postsynaptic potentials in these neurons is a product of two components that vary with either ITD or ILD. Temporal correlation in the fine structure of signals between the ears is essential for detection of ITD. By varying the degree of binaural correlation, we could accurately change the amplitude of the ITD component of postsynaptic potentials in the space-specific neurons. Multiplication worked for the entire range of postsynaptic potentials created by manipulation of ITD.

Bilateral matching of frequency tuning in neural cross-correlators of the owl

Sound localization requires comparison between the inputs to the left and right ears. One important aspect of this comparison is the differences in arrival time to each side, also called interaural time difference (ITD). A prevalent model of ITD detection, consisting of delay lines and coincidence-detector neurons, was proposed by Jeffress (J Comp Physiol Psychol 41:35–39, 1948). As an extension of the Jeffress model, the process of detecting and encoding ITD has been compared to an effective cross-correlation between the input signals to the two ears. Because the cochlea performs a spectrotemporal decomposition of the input signal, this cross-correlation takes place over narrow frequency bands. Since the cochlear tonotopy is arranged in series, sounds of different frequencies will trigger neural activity with different temporal delays. Thus, the matching of the frequency tuning of the left and right inputs to the cross-correlator units becomes a ‘timing’ issue. These properties of auditory transduction gave theoretical support to an alternative model of ITD-detection based on a bilateral mismatch in frequency tuning, called the ‘stereausis’ model. Here we first review the current literature on the owl’s nucleus laminaris, the equivalent to the medial superior olive of mammals, which is the site where ITD is detected. Subsequently, we use reverse correlation analysis and stimulation with uncorrelated sounds to extract the effective monaural inputs to the cross-correlator neurons. We show that when the left and right inputs to the cross-correlators are defined in this manner, the computation performed by coincidence-detector neurons satisfies conditions of cross-correlation theory. We also show that the spectra of left and right inputs are matched, which is consistent with predictions made by the classic model put forth by Jeffress.

Effect of instantaneous frequency glides on interaural time difference processing by auditory coincidence detectors

Detecting interaural time difference (ITD) is crucial for sound localization. The temporal accuracy required to detect ITD, and how ITD is initially encoded, continue to puzzle scientists. A fundamental question is whether the monaural inputs to the binaural ITD detectors differ only in their timing, when temporal and spectral tunings are largely inseparable in the auditory pathway. Here, we investigate the spectrotemporal selectivity of the monaural inputs to ITD detector neurons of the owl. We found that these inputs are selective for instantaneous frequency glides. Modeling shows that ITD tuning depends strongly on whether the monaural inputs are spectrotemporally matched, an effect that may generalize to mammals. We compare the spectrotemporal selectivity of monaural inputs of ITD detector neurons in vivo, demonstrating that their selectivity matches. Finally, we show that this refinement can develop through spike timing-dependent plasticity. Our findings raise the unexplored issue of time-dependent frequency tuning in auditory coincidence detectors and offer a unifying perspective.

Auditory Spatial Tuning at the Crossroads of the Midbrain and Forebrain

The barn owls midbrain and forebrain contain neurons tuned to sound direction. The spatial receptive fields of these neurons result from sensitivity to combinations of interaural time (ITD) and level (ILD) differences over a broad frequency range. While a map of auditory space has been described in the midbrain, no similar topographic representation has been found in the forebrain. The first nuclei that belong exclusively to the forebrain and midbrain pathways are the thalamic nucleus ovoidalis (Ov) and the external nucleus of the inferior colliculus (ICx), respectively. The midbrain projects to the auditory thalamus before sharp spatial receptive fields emerge; although Ov and ICx receive projections from the same midbrain nuclei, they are not directly connected. We compared the spatial tuning in Ov and ICx. Thalamic neurons respond to a broader frequency range and their ITD and ILD tuning varied more across frequency. However, neurons in Ov showed spatial receptive fields as selective as neurons in ICx. Thalamic spatial receptive fields were tuned to frontal and contralateral space and correlated with their tuning to ITD and ILD. Our results indicate that spatial tuning emerges in both pathways by similar combination selectivity to ITD and ILD. However, the midbrain and the thalamus do not appear to repeat exactly the same processing, as indicated by the difference in frequency range and the broader tuning to binaural cues. The differences observed at the initial stages of these sound-localization pathways may reflect diverse functions and coding schemes of midbrain and forebrain.