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Nelken, I.

Publications and source records attributed to Nelken, I..

17 recordsLinked to original sources

Predictive abstract task representations support few-shot learning in the rat brain

Few-shot learning reveals core mechanisms of flexible cognition and adaptive decision- making in animal behavior by showing how animals rapidly infer rules, categories, or action strategies from sparse experience. Few-shot learning often depends on abstract representations that capture task structure and generalize across similar instances of the same task. The orbitofrontal cortex (OFC) is known to encode abstract representations, but whether these representations can adapt to new contingencies at the rapid timescale of few-shot learning is unknown. We trained rats on a sequence-learning task with recurring structure but changing contingencies. Rats demonstrated few-shot learning, reaching near-optimal performance within 2-3 rewards after each contingency change, exploiting the tasks recurring structure to rapidly generalize across sequence blocks. We recorded OFC activity using Neuropixels probes during task performance. The firing rate of OFC units in the few seconds preceding each poke encoded the task state and predicted the selected action. Remarkably, this predictive activity also encoded the abstract notion of role: the function of an action under the current contingencies. Role representations in the OFC changed on the same rapid timescale as the behavioral changes. We suggest that few-shot learning in this task is supported by the rapid remapping of roles onto actions.

neuroscience↗

Auditory responses in the ventral tegmental area of awake, freely moving mice

The ventral tegmental area (VTA) is a key region in the reward system of the vertebrate brain, yet its role in sensory processing remains largely unexplored. Here, we use fiber photometry in awake freely-moving mice to investigate how the VTA represents auditory stimuli. We compared VTA responses to those in the inferior colliculus (IC) recorded with the same technique. Neural activity in the VTA exhibited robust responses to a wide variety of auditory stimuli, including broadband noise, pure tones, and music stimuli. We identified a subset of short-latency trials, comparable to those observed in the IC, with response durations that were longer than in the IC. VTA responses to complex sounds showed minimal envelope tracking and low temporal reproducibility, resulting in poor discriminability. This study positions the VTA as a potentially active player in shaping the perception of sound.

neuroscience↗

Parsing auditory neural code into maximum-entropy packets

Deciphering the neural code requires identifying its fundamental symbols or code-words. Neural activity is usually interpreted either as a rate code - based on average spike counts - or as a temporal code, which distinguishes patterns with identical counts. Yet, the symbols of the code remain undefined. Here we show that the symbols can be clearly defined by parsing auditory spike trains into variable-duration "packets", within which precise spike timing is irrelevant. Because packets vary in duration, this is not a rate code. A single neuron could encode very different stimuli depending on the number of spikes it produced per packet. The packet-based code enables real-time readout upon packet completion due to its instantaneous code structure and maximizes information capacity at both single-neuron and population levels.

neuroscience↗

The representation of regularity and randomness in auditory cortex of awake rats

Auditory cortex possesses a remarkable ability to discriminate between tone sequences with different levels of statistical regularities. To examine this phenomenon at the level of single neurons, we recorded responses from auditory cortex of awake rats. The rats passively listened to multitone sequences composed of 4, 5 or 6 tones. The tones could be presented in periodic sequences with a fixed, repeated cycle; in a fully random condition; or in an intermediate condition in which cycles were maintained but tones were randomly permuted within each cycle (random cycle condition). Units showed a continuum of preferences between order-preferring neurons and randomness-preferring neurons. Unexpectedly, we found sensitivity to the position of sounds in the cycle ( phase modulation). The strongest and most consistent phase modulations were in the responses to the random cycle condition. Finally, we show how such sensitivities may emerge from a simple, biologically- plausible computation.

neuroscience↗

Insular cortex encodes task alignment

Animals can learn complex behaviors. Animal behavior in the lab has traditionally been studied via summary statistics such as trial-based success rates. However, animal behavior is much more fine-grained: a trial in an experiment often consists of multiple actions, and more than one strategy can lead to a successful completion of a trial. To understand how the brain controls behavior, a fine-grained yet compact description of behavior is necessary. We describe here an approach for estimating the strategies animals use for a large family of tasks from first principles. Using reinforcement learning with informational constraints on policies, we compute a rich set of candidate policies with a small number of meaningful parameters, and match observed behavior to these policies. In a sample rat task, our approach revealed ongoing learning for more than 100 days after the saturation of success rates. Moreover, we showed that many neurons in the insular cortex of rats track the instantaneous task engagement of the rats with a resolution of a few minutes. Due to its generic formulation in reinforcement learning terminology, our work is directly applicable to the majority of animal tasks in use today.

neuroscience↗

Task-related activity in auditory cortex enhances sound representation

In auditory-guided tasks, sound presentations often occupy a small fraction of the total task time. We studied here neuronal dynamics that spanned trial duration. Many neurons had large, slow, firing rate modulations, which were not driven by sounds, were larger than the sound evoked responses, and were locked to specific time points during the task, similar to responses of hippocampal time-sensitive neurons. Concurrently, responses to sounds differed between active behavior and passive listening conditions: in the active sessions, the on-going activity just before sound presentations was higher and the responses to target stimuli were weaker but more informative about the task-relevant sounds. We show that the slow firing rate modulations caused the increased on-going activity. Using a model, we demonstrate that higher on-going activity led to more synaptic depression of the cortico-cortical synapses, reducing the tendency to produce population spikes and resulting in weaker but more informative responses.

neuroscience↗

Sound preferences in mice are sex-dependent

We investigated the impact of early exposure to sound and to silence on sound preferences later in life in mice. We exposed young mice during the critical periods to excerpts of music (first movement of Beethovens symphony no. 9), non-music sounds, or to silence. We tested the sound preference behavior a few weeks later. Music exposure affected mouse behavior in a sex- dependent manner: male mice largely preferred the environment to which they were exposed, while female mice showed a weak reduction in their seemingly inborn aversion to sound. The neural activity in auditory cortex was suppressed in exposed compared to naive mice, regardless of exposure type. Remarkably, a robust negative correlation was found between neural response and behavior in female, but not in male, mice.

neuroscience↗

Evaluating Cochlear Implant Stimulation Strategies Through Wide-field Calcium Imaging of the Auditory Cortex

Cochlear Implants (CI) are an effective neuroprosthesis for humans with profound hearing loss, enabling deaf adults to have phone calls without lipreading and babies to have successful language development. However, CIs have significant limitations in complex hearing situations, motivating the need for further research, including studies in animal models. Here, we demonstrate the usefulness of wide field Ca++ imaging in assessing different CI stimulation strategies. One major challenge in electrophysiology in CI animals lies in excluding the CI electric artifacts from the recording, since they are orders of magnitude larger than the amplitude of action potentials. Also, electrophysiology can rarely sample large areas of neuropil at high spatial resolution. To circumvent these problems, we have set up an imaging system allowing us to monitor neural activity in the auditory cortex (AC) of CI supplied rats using the Ca++ sensitive dye OGB. Here we describe an initial experiment with this setup, in which we recorded cortical responses to 4 different stimulation patterns which were delivered across 3 CI channels to the contralateral ear. We then investigated two parameters that have been shown to affect intelligibility in CI users: pulse rate and relative pulse timing across CI channels. While pulse rate had only a very modest effect on the discriminability of the neural responses, the stimulation mode had a major effect, with simultaneous pulse timing, perhaps surprisingly, allowing much better pattern discrimination than interleaved sampling. The result suggests that allowing collisions of pulses on neighboring channels may not always be detrimental, at least if partial overlaps of pulses, in which anodic and cathodic pulse phases might cancel, are avoided.

neuroscience↗

A Rapid Anterior Auditory Processing Stream Through the Insulo-Parietal Auditory Field in the Rat

The insular cortex is believed to be involved in a wide range of auditory functions in the mammalian brain. We studied the organization and basic response properties of auditory neurons in insular cortex and adjacent areas by recording responses to sound stimuli in anesthetized rats. Auditory neurons were present in an insulo-parietal auditory field that spans the boundary between the posterior insula, particularly in the granular insular cortex and the ventral part of the secondary somatosensory cortex. Neurons in this field had narrow tuning, were preferentially tuned to relatively low frequencies (<16 kHz), and had short response latencies. Intriguingly, some auditory units in this insulo-parietal field displayed shorter onset latencies than the minimal latency in primary auditory cortex. At the same time, these units showed weaker sensitivity to deviance than units in primary auditory cortex. These results establish the existence of a rapid information stream through the insulo-parietal cortex that may parallel the pathway through the primary and anterior auditory fields.

neuroscience↗

Rats synchronize predictively to metronomes

Humans easily and naturally synchronize their motor activity to music, a behavior unparalleled by other species. As a consequence of the mystery surrounding its evolutionary and biological origins, there is rapidly growing interest in exploring the capacity of nonhuman species to synchronize motor activity with auditory rhythms. The hallmark observation in human studies is that synchronization is predictive. Given the highly variable behaviors observed in other animals, it is particularly difficult to distinguish a predictive synchronization behavior from one that perhaps resembles it, but relies on simpler strategies. Here, we introduce a novel modeling approach that quantitatively compares candidate strategies for explaining observed behaviors. Eight rats synchronized to metronomes across a range of tempi (0.5-2 Hz), and immediate water reward was delivered whenever they initiated a lick burst within a short time window around beats. We observed a roughly constant baseline lick probability throughout, with a [~]30% modulation of the lick rate around beats. We fitted to the results six candidate models, ranging from an insensitive model assuming that rats lick at random, to predictive models where rats suppress licking between beats for a tempo-dependent duration of time. The predictive model consistently outperformed other models, including a reactive model, demonstrating that rats synchronize predictively to auditory metronomes.

neuroscience↗

Prior unsupervised experience leads to long lasting effects in sensory gating during discrimination learning

As the animal moves in its environment, the brain detects and learns the structure of the surrounding stimuli, independently of the immediate relevance this has for the animal. This experience influences subsequent learning in a manner quantified using paradigms such as latent inhibition or stimulus preconditioning, which measure the effect that unsupervised (not-reinforced) learning has on subsequent reinforced learning. Despite our understanding of the behavioural consequences of prior neutral experience, there is little understanding about the influence of this previous experience on neuronal plasticity. Using latent inhibition, we have shown in mice that learning a two tone discrimination is slower in mice that have had previous neutral exposure to the same or similar tones (<2/3 octave away). Neutral exposure thus elicits profound changes in the brain that influence subsequent learning. To study how previous experience influences experience-dependent plasticity, and better understand the interactions between experience, learning, and plasticity, we recorded sound evoked responses in the auditory cortex of exposed and trained mice. We studied both changes in response magnitude and changes in sensory dynamics, and related both to the differential behavioral effects of different pre-exposure conditions. Here we describe the neuronal changes that paralleled the behavioral findings. We found that discrimination learning led to stronger initial sound-evoked responses and a long-lasting increase in response adaptation and an increase. The first effect was delayed in animals that showed latent inhibition, paralleling behavioural learning. Overall our data reveal that slow changes in behaviour that accompanied learning, paralleled the slow dynamics of experience-dependent plasticity in auditory cortex.

neuroscience↗

The RIFF: an automated environment for studying the neural basis of auditory-guided complex behavior

Behavior consists of the interaction between an organism and its environment, and is controlled by the brain. Brain activity varies at sub-second time scales, but behavioral measures are usually coarse (often consisting of only binary trial outcomes). To overcome this mismatch, we developed the RIFF: a programmable interactive arena for freely-moving rats with multiple feeding areas, multiple sound sources, high-resolution behavioral tracking, and simultaneous electrophysiological recordings. We describe two complex tasks implemented in the RIFF. Rats quickly learned these tasks and developed anticipatory behavior. Neurons in auditory cortex and posterior insula showed sensitivity to non-auditory parameters such as location and pose. Our combination of wireless electrophysiology and detailed behavioral documentation in a controlled environment produces insights into the cognitive capabilities and learning mechanisms of rats and opens the way to a better understanding of how brains control behavior.

neuroscience↗

Context Sensitivity Across Multiple Time and Frequency Scales

Everyday auditory streams are complex, including spectro-temporal content that varies at multiple time scales. Using EEG, we investigate the sensitivity of human auditory cortex to the content of past stimulation in unattended sequences of equiprobable tones. In 3 experiments including 82 participants overall, we found that neural responses measured at different latencies after stimulus onset were sensitive to frequency intervals computed over distinct time scales. Importantly, early responses were sensitive to a longer history of stimulation than later responses. To account for these results, we tested a model consisting of neural populations with frequency-specific but broad tuning that undergo adaptation with exponential recovery. We found that the coexistence of neural populations with distinct recovery rates can explain our results. Furthermore, the adaptation bandwidth of these populations depended on spectral context - it was wider when the stimulation sequence had a wider frequency range. Our results provide electrophysiological evidence as well as a possible mechanistic explanation for dynamic and multi-scale context-dependent auditory processing in the human cortex. SIGNIFICANCE STATEMENTIt has become clear that brain processing of sensory stimuli depends on their temporal context, but context can be construed at time scales from the recent millisecond to life-long. How do different contextual time scales affect sensory processing? We show that auditory context is integrated across at least two separate time scales, and that at both of these time scales responses dynamically adapt to a varying frequency stimulation range. Using computational modeling, we develop a rigorous methodology to estimate the time and frequency scales of context integration for separate response components. Our robust results replicated across 3 EEG experiments, and contribute to the understanding of neural mechanisms supporting complex and dynamic context integration.

neuroscience↗

Dense Computer Replica of Cortical Microcircuits Unravels Cellular Underpinnings of Auditory Surprise Response

The nervous system is notorious for its strong response evoked by a surprising sensory input, but the biophysical and anatomical underpinnings of this phenomenon are only partially understood. Here we utilized in-silico experiments of a biologically-detailed model of a neocortical microcircuit to study stimulus specific adaptation (SSA) in the auditory cortex, whereby the neuronal response adapts significantly for a repeated ("expected") tone but not for a rare ("surprise") tone. SSA experiments were mimicked by stimulating tonotopically-mapped thalamo-cortical afferents projecting to the microcircuit; the activity of these afferents was modeled based on our in-vivo recordings from individual thalamic neurons. The modeled microcircuit expressed naturally many experimentally-observed properties of SSA, suggesting that SSA is a general property of neocortical microcircuits. By systematically modulating circuit parameters, we found that key features of SSA depended on synergistic effects of synaptic depression, spike frequency adaptation and recurrent network connectivity. The relative contribution of each of these mechanisms in shaping SSA was explored, additional SSA-related experimental results were explained and new experiments for further studying SSA were suggested.

neuroscience↗

Stimulus-specific adaptation to behaviorally-relevant sounds in awake rats

Stimulus-specific adaptation (SSA) is the reduction in responses to a common stimulus that does not generalize, or only partially generalizes, to other stimuli. SSA has been studied mainly with sounds that bear no behavioral meaning. We hypothesized that the acquisition of behavioral meaning by a sound should modify the amount of SSA evoked by that sound. To test this hypothesis, we used fear conditioning in rats, using two word-like stimuli, derived from the English words \"danger\" and \"safety\", as well as pure tones. One stimulus (CS+) was associated with a foot shock whereas the other stimulus (CS-) was presented without a concomitant foot shock. We recorded neural responses to the auditory stimuli using chronically implanted multi-electrode arrays, recording responses telemetrically in freely moving animals before and after conditioning. Consistent with our hypothesis, SSA changed in a way that depended on the behavioral role of the sound: the contrast between standard and deviant responses remained the same or decreased for CS+ stimuli but increased for CS- stimuli, showing that SSA is shaped by experience. In most cases the sensory responses underlying these changes in SSA increased following conditioning. Unexpectedly, the responses to CS+ word-like stimuli showed a specific, substantial decrease, which we interpret as evidence for substantial inhibitory plasticity.

neuroscience↗

Multiple timescales account for adaptive responses across sensory cortices

Sensory systems encounter remarkably diverse stimuli in the external environment. Natural stimuli exhibit timescales and amplitudes of variation that span a wide range. Mechanisms of adaptation, ubiquitous feature of sensory systems, allow for the accommodation of this range of scales. Are there common rules of adaptation across different sensory modalities? We measured the membrane potential responses of individual neurons in the visual, somatosensory and auditory cortices to discrete, punctate stimuli delivered at a wide range of fixed and nonfixed frequencies. We find that the adaptive profile of the response is largely preserved across these three areas, exhibiting attenuation and responses to the cessation of stimulation which are signatures of response to changes in stimulus statistics. We demonstrate that these adaptive responses can emerge from a simple model based on the integration of fixed filters operating over multiple time scales.

neuroscience↗

Acoustic Calibration in an Echoic Environment

Background: The sound fed to a loudspeaker may significantly differ from that reaching the ear of the listener. The transformation from one to the other consists of spectral distortions with strong dependence on the relative locations of the speaker and the listener as well as on the geometry of the environment. With the increased importance of research in awake, freely-moving animals in large arenas, it becomes important to understand how animal location influences the corresponding spectral distortions.\n\nNew Method: We describe a full calibration pipeline that includes spatial sampling and estimation of the spectral distortions. We estimated the impulse responses of the environment using Golay complementary sequences.\n\nUsing those sequences, we also describe an acoustic 3D localization method for freely moving animals.\n\nResults: In our arena, the impulse responses are dominated by a small number of strong reflections. We use this understanding to provide guidelines for designing the geometry of the environment as well as the presented sounds, in order to provide more uniform sound levels throughout the environment. Our 3D localization method achieves a 1 cm precision through the utilization of sound cues only.\n\nComparison with Existing Methods: To our knowledge, this is the first description of a large-scale acoustic calibration pipeline with acoustic localization for neuroscience studies.\n\nConclusions: Principled sampling of large arena allows for better design and control of the acoustic information provided to freely-moving animals.

animal behavior and cognition↗