Behavioral Neuroscience publications

Cannabinoids have been suggested as a therapeutic target for a variety of brain disorders. Despite the presence of their receptors throughout the auditory system, little is known about how cannabinoids affect auditory function. We sought to determine whether administration of arachidonyl-2'-chloroethylamide (ACEA), a highly-selective CB1 agonist, could attenuate a variety of auditory effects caused by prior administration of salicylate, and potentially treat tinnitus. We recorded cortical resting-state activity, auditory-evoked cortical activity and auditory brainstem responses (ABRs), from chronically-implanted awake guinea pigs, before and after salicylate + ACEA. Salicylate-induced reductions in click-evoked ABR amplitudes were smaller in the presence of ACEA, suggesting that the ototoxic effects of salicylate were less severe. ACEA also abolished salicylate-induced changes in cortical alpha band (6-10 Hz) oscillatory activity. However, salicylate-induced increases in cortical evoked activity (suggestive of the presence of hyperacusis) were still present with salicylate + ACEA. ACEA administered alone did not induce significant changes in either ABR amplitudes or oscillatory activity, but did increase cortical evoked potentials. Furthermore, in two separate groups of non-implanted animals, we found no evidence that ACEA could reverse behavioural identification of salicylate- or noise-induced tinnitus. Together, these data suggest that while ACEA may be potentially otoprotective, selective CB1 agonists are not effective in diminishing the presence of tinnitus or hyperacusis.

The mechanisms underlying multi-sensory interactions are still poorly understood despite considerable progress made since the first neurophysiological recordings of multi-sensory neurons. While the majority of single-cell neurophysiology has been performed in anesthetized or passive-awake laboratory animals, the vast majority of behavioral data stems from studies with human subjects. Interpretation of neurophysiological data implicitly assumes that laboratory animals exhibit perceptual phenomena comparable or identical to those observed in human subjects. To explicitly test this underlying assumption, we here characterized how two rhesus macaques and four humans detect changes in intensity of auditory, visual, and audio-visual stimuli. These intensity changes consisted of a gradual envelope modulation for the sound, and a luminance step for the LED. Subjects had to detect any perceived intensity change as fast as possible. By comparing the monkeys' results with those obtained from the human subjects we found that (1) unimodal reaction times differed across modality, acoustic modulation frequency, and species, (2) the largest facilitation of reaction times with the audio-visual stimuli was observed when stimulus onset asynchronies were such that the unimodal reactions would occur at the same time (response, rather than physical synchrony), and (3) the largest audio-visual reaction-time facilitation was observed when unimodal auditory stimuli were difficult to detect, i.e., at slow unimodal reaction times. We conclude that despite marked unimodal heterogeneity, similar multisensory rules applied to both species. Single-cell neurophysiology in the rhesus macaque may therefore yield valuable insights into the mechanisms governing audio-visual integration that may be informative of the processes taking place in the human brain.

Approximately 15% of American adults report some degree of difficulty hearing in a noisy environment or have auditory filtering difficulties. There are objective clinical tests of auditory filtering, yet few tests exist for mouse models that do not rely on extensive training. We have used reflex modification audiometry (RMA) and developed exclusion criteria for the mouse model. This RMA based test makes use of the acoustic startle response (ASR) and the ability of prepulses to inhibit the ASR [i.e., prepulse inhibition (PPI)] to assess the mouse's ability to detect prepulse signals presented in quiet or embedded in masking noise. We have studied PPI behavior across four inbred mouse strains with normal cochlear function and developed pre-testing exclusion criteria and test/retest reliability measures. Moreover, because both the medial (MOC) and the lateral (LOC) olivocochlear efferent feedback systems have been proposed to improve auditory behavior performance, especially in noisy backgrounds, we have examined PPI abilities in mice (with their littermate controls) either lacking the MOC receptor subunit α9 nicotinic acetylcholine receptor [α9 nAChR (-/-)] or expressing an overactive receptor [Ld'T mutation in α9 nAChR KI], or lacking an LOC efferent neuropeptide, alpha calcitonin gene-related peptide [αCGRP (-/-)] only in the CNS. Because CGRP receptor formation has been shown to mature from juvenile to adult ages, we also studied if this maturation would be reflected in PPI behavioral responses in juvenile and adult (+/+) controls and in adult αCGRP (-/-) animals. We show that 50% PPI response thresholds (sound level with 50% correct responses) in quiet are decreased in the (-/-) α9 nAChR animals, and 50% PPI responses are increased for mice with an overactive receptor (α9 nAChR KI) and are increased in adult mice lacking αCGRP (-/-). However, in background noise, only mice lacking αCGRP exhibited increased 50% PPI response thresholds, as there were no significant differences between α9 nAChR adult mouse lines and their littermate controls. These findings suggest that MOC and LOC olivocochlear neurotransmission work in tandem to improve behavioral responses to sound. These experiments further pave the way for rapid behavioral hearing assessments in other mouse models.

The hippocampus is known as a neuronal structure involved in learning, memory and spatial navigation using multi-sensory cues. However, the basic features of its response to acoustic stimuli without any behavioral tasks (conditioning) remains poorly studied. Here, we investigated the CA3 response to auditory stimuli using in vivo loose-patch recordings in awake and anesthetized C57 mice. Different acoustic stimuli in addition to broadband noise such as click, FM sound and pure tone were applied to test the response of CA3 in awake animals. It was found that the wakefulness of the animal is important for the recorded neurons to respond. The CA3 neurons showed a stronger response to broadband noise rather than the other type of stimuli which suggested that auditory information arrived at CA3 via broadband pathways. Finally, we investigated the excitatory and inhibitory inputs to CA3 neurons by using in vivo whole-cell voltage-clamp techniques with the membrane potential holding at -70 and 0 mV, respectively. In awake animals, the excitatory and inhibitory inputs CA3 neurons receive induced by noise are balanced by showing stable intervals and proportional changes of their latencies and peak amplitudes as a function of the stimulation intensities.

BLA neurons serve a well-accepted role in fear conditioning and fear extinction. However, the specific learning processes related to their activity at different times during learning remain poorly understood. We addressed this using behavioral tasks isolating distinct aspects of fear learning in male rats. We show that brief optogenetic inhibition of BLA neurons around moments of aversive reinforcement or nonreinforcement causes reductions in the salience of conditioned stimuli, rendering these stimuli less able to be learned about and less able to control fear or safety behaviors. This salience reduction was stimulus-specific, long-lasting, and specific to learning about, or responding to, the same aversive outcome, precisely the goals of therapeutic interventions in human anxiety disorders. Our findings identify a core learning process disrupted by brief BLA optogenetic inhibition. They show that a primary function of the unconditioned stimulus-evoked activity of BLA neurons is to maintain the salience of conditioned stimuli that precede it. This maintenance of salience is a necessary precursor for these stimuli to gain and maintain control over fear and safety behavior. SIGNIFICANCE STATEMENT The amygdala is essential for learning to fear and learning to reduce fear. However, the specific roles served by activity of different amygdala neurons at different times during learning is poorly understood. We used behavioral tasks isolating distinct aspects of learning in rats to show that brief optogenetic inhibition of BLA neurons around moments of reinforcement or nonreinforcement disrupts maintenance of conditioned stimulus salience. This causes a stimulus-specific and long-lasting deficit in the ability of the conditioned stimulus to be learned about or control fear responses. These consequences are the precisely goals of therapeutic interventions in human anxiety disorders. Our findings identify a core learning process disrupted by brief BLA optogenetic inhibition.

Males of a trilling species in the Mecopoda complex produce conspicuous calling songs that consist of two motifs: an amplitude-modulated motif with alternating loud and soft segments (AM-motif) and a continuous, high-intensity trill. The function of these song motifs for female attraction and competition between males was investigated. We tested the hypothesis that males modify their signaling behavior depending on the social environment (presence/absence of females or rival males) when they compete for mates. Therefore, we analyzed acoustic signaling of males in three different situations: (1) solo singing, (2) acoustic interaction with another male, and (3) singing in the presence of a female. In addition, the preference of females for these song motifs and further song parameters was studied in two-choice experiments. As expected, females showed a preference for conspicuous and loud song elements, but nevertheless, males increased the proportion of the AM-motif in the presence of a female. In acoustic interactions, males reduced bout duration significantly compared to both other situations. However, song bouts in this situation still overlapped more than expected by chance, which indicates intentionally simultaneous singing. A multivariate statistical analysis revealed that the proportion of the AM-motif and the duration of loud segments within the AM-motif allow a reliable prediction of whether males sing in isolation, compete with another male, or sing in the presence of a female. These results indicate that the AM-motif plays a dominant role especially in close-range courtship and that males are challenged in finding a balance between attracting females and saving energy during repeated acoustic interactions. Significance statement: Males of acoustic insects often produce conspicuous calling songs that have a dual function in male-male competition and mate attraction. High signal amplitudes and signal rates are associated with high energetic costs for signal production. We would therefore predict that males adjust their signaling behavior according to their perception of the social context. Here we studied signal production and mate choice in a katydid, where males switch between loud and soft song segments in a dynamic way. Additionally, we examined the attractiveness of different song elements in female choice tests. Our results show how males of this katydid deal with the conflict of remaining attractive for females and competing with a costly signal with rivals.

The integration of multiple sensory modalities is a key aspect of brain function, allowing animals to take advantage of concurrent sources of information to make more accurate perceptual judgments. For many years, multisensory integration in the cerebral cortex was deemed to occur only in high-level “polysensory” association areas. However, more recent studies have suggested that cross-modal stimulation can also influence neural activity in areas traditionally considered to be unimodal. In particular, several human neuroimaging studies have reported that extrastriate areas involved in visual motion perception are also activated by auditory motion, and may integrate audio-visual motion cues. However, the exact nature and extent of the effects of auditory motion on the visual cortex have not been studied at the single neuron level. We recorded the spiking activity of neurons in the middle temporal (MT) and medial superior temporal (MST) areas of anesthetized marmoset monkeys upon presentation of unimodal stimuli (moving auditory or visual patterns), as well as bimodal stimuli (concurrent audio-visual motion). Despite robust, direction selective responses to visual motion, none of the sampled neurons responded to auditory motion stimuli. Moreover, concurrent moving auditory stimuli had no significant effect on the ability of single MT and MST neurons, or populations of simultaneously recorded neurons, to discriminate the direction of motion of visual stimuli (moving random dot patterns with varying levels of motion noise). Our findings do not support the hypothesis that direct interactions between MT, MST and areas low in the hierarchy of auditory areas underlie audiovisual motion integration.

Brain-specific link protein Bral2 represents a substantial component of perineuronal nets (PNNs) enwrapping neurons in the central nervous system. To elucidate the role of Bral2 in auditory signal processing, the hearing function in knockout Bral2-/- (KO) mice was investigated using behavioral and electrophysiological methods and compared with wild type Bral2+/+ (WT) mice. The amplitudes of the acoustic startle reflex (ASR) and the efficiency of the prepulse inhibition of ASR (PPI of ASR), produced by prepulse noise stimulus or gap in continuous noise, was similar in 2-week-old WT and KO mice. Over the 2-month postnatal period the increase of ASR amplitudes was significantly more evident in WT mice than in KO mice. The efficiency of the PPI of ASR significantly increased in the 2-month postnatal period in WT mice, whereas in KO mice the PPI efficiency did not change. Hearing thresholds in 2-month-old WT mice, based on the auditory brainstem response (ABR) recordings, were significantly lower at high frequencies than in KO mice. However, amplitudes and peak latencies of individual waves of click-evoked ABR did not differ significantly between WT and KO mice. Temporal resolution and neural adaptation were significantly better in 2-month-old WT mice than in age-matched KO mice. These results support a hypothesis that the absence of perineuronal net formation at the end of the developmental period in the KO mice results in higher hearing threshold at high frequencies and weaker temporal resolution ability in adult KO animals compared to WT mice.

Rodents lick to consume fluids. The reward value of ingested fluids is likely to be encoded by neuronal activity entrained to the lick cycle. Here, we investigated relationships between licking and reward signaling by the medial frontal cortex (MFC), a key cortical region for reward-guided learning and decision-making. Multielectrode recordings of spike activity and field potentials were made in male rats as they performed an incentive contrast licking task. Rats received access to higher- and lower-value sucrose rewards over alternating 30 s periods. They learned to lick persistently when higher-value rewards were available and to suppress licking when lower-value rewards were available. Spectral analysis of spikes and fields revealed evidence for reward value being encoded by the strength of phase-locking of a 6–12 Hz theta rhythm to the rats' lick cycle. Recordings during the initial acquisition of the task found that the strength of phase-locking to the lick cycle was strengthened with experience. A modification of the task, with a temporal gap of 2 s added between reward deliveries, found that the rhythmic signals persisted during periods of dry licking, a finding that suggests the MFC encodes either the value of the currently available reward or the vigor with which rats act to consume it. Finally, we found that reversible inactivations of the MFC in the opposite hemisphere eliminated the encoding of reward information. Together, our findings establish that a 6–12 Hz theta rhythm, generated by the rodent MFC, is synchronized to rewarded actions. SIGNIFICANCE STATEMENT The cellular and behavioral mechanisms of reward signaling by the medial frontal cortex (MFC) have not been resolved. We report evidence for a 6–12 Hz theta rhythm that is generated by the MFC and synchronized with ongoing consummatory actions. Previous studies of MFC reward signaling have inferred value coding upon temporally sustained activity during the period of reward consumption. Our findings suggest that MFC activity is temporally sustained due to the consumption of the rewarding fluids, and not necessarily the abstract properties of the rewarding fluid. Two other major findings were that the MFC reward signals persist beyond the period of fluid delivery and are generated by neurons within the MFC.

Following learning, increased coupling between spindle oscillations in the medial prefrontal cortex (mPFC) and ripple oscillations in the hippocampus is thought to underlie memory consolidation. However, whether learning-induced increases in ripple-spindle coupling are necessary for successful memory consolidation has not been tested directly. In order to decouple ripple-spindle oscillations, here we chemogenetically inhibited parvalbumin-positive (PV+) interneurons, since their activity is important for regulating the timing of spiking activity during oscillations. We found that contextual fear conditioning increased ripple-spindle coupling in mice. However, inhibition of PV+ cells in either CA1 or mPFC eliminated this learning-induced increase in ripple-spindle coupling without affecting ripple or spindle incidence. Consistent with the hypothesized importance of ripple-spindle coupling in memory consolidation, post-training inhibition of PV+ cells disrupted contextual fear memory consolidation. These results indicate that successful memory consolidation requires coherent hippocampal-neocortical communication mediated by PV+ cells.

The ability to discriminate modulation frequencies is important for speech intelligibility because speech has amplitude and frequency modulations. Neurophysiological responses assessed by envelope following responses (EFRs) significantly decline at faster amplitude modulation frequencies (AMF) in older subjects. A typical assumption is that a decline in EFRs will necessarily result in corresponding perceptual deficits. To test this assumption, we investigated young and aged Fischer-344 rats’ behavioral AMF discrimination abilities and compared to their EFRs. A modified version of prepulse inhibition (PPI) of acoustic startle reflex (ASR) was used to obtain behavioral performance. A PPI trial contains pulses of sinusoidal AM (SAM) at 128 Hz presented sequentially, a SAM prepulse with different AMF and a startle-eliciting-stimulus. To account for hearing threshold shift or age-related synaptopathy, stimulus levels were presented at 10-dB lower or match to the aged peripheral neural activation (using auditory brainstem response wave I amplitude). When AMF differences and modulation depths were large, young and aged animals’ behavioral performances were comparable. Aged animals’ AMF discrimination abilities declined as the AMF difference or the modulation depth reduced, even compared to the young with peripheral matching. Young animals showed smaller relative decreases in EFRs with reduced modulation depths. The correlation of EFRs and AM perception was identified to be more consistent in young animals. The overall results revealed larger age-related deficits in behavioral perception compared to EFRs, suggesting additional factors that affect perception despite smaller degradation in neural responses. Hence, behavioral and physiological measurements are critical in unveiling a more complete picture on the auditory function.

Increasing evidence suggests that cortical dynamics during wake exhibits long-range temporal correlations suitable to integrate inputs over extended periods of time to increase the signal-to-noise ratio in decision making and working memory tasks. Accordingly, sleep has been suggested as a state characterized by a breakdown of long-range correlations. However, detailed measurements of neuronal timescales that support this view have so far been lacking. Here, we show that the cortical timescales measured at the individual neuron level in freely behaving male rats change as a function of vigilance state and time awake. Although quiet wake and rapid eye movement (REM) sleep are characterized by similar, long timescales, these long timescales are abrogated in non-REM sleep. We observe that cortex dynamics exhibits rapid transitions between long-timescale states and sleep-like states governed by short timescales even during wake. This becomes particularly evident during sleep deprivation, when the interplay between these states can lead to an increasing disruption of long timescales that are restored after sleep. Experiments and modeling identify the intrusion of neuronal offline periods as a mechanism that disrupts the long timescales arising from reverberating cortical network activity. Our results provide novel mechanistic and functional links among behavioral manifestations of sleep, wake, and sleep deprivation and specific measurable changes in the network dynamics relevant for characterizing the brain's changing information-processing capabilities. They suggest a network-level function of sleep to reorganize cortical networks toward states governed by long timescales to ensure efficient information integration for the time awake. SIGNIFICANCE STATEMENT Lack of sleep deteriorates several key cognitive functions, yet the neuronal underpinnings of these deficits have remained elusive. Cognitive capabilities are generally believed to benefit from a neural circuit's ability to reliably integrate information. Persistent network activity characterized by long timescales may provide the basis for this integration in cortex. Here, we show that long-range temporal correlations indicated by slowly decaying autocorrelation functions in neuronal activity are dependent on vigilance states. Although wake and rapid eye movement (REM) sleep exhibit long timescales, these long-range correlations break down during non-REM sleep. Our findings thus suggest two distinct states in terms of timescale dynamics. During extended wake, the rapid switching to sleep-like states with short timescales can lead to an overall decline in cortical timescales.

We measured the auditory sensitivity of the barn owl ( Tyto alba ), using a behavioural Go/NoGo paradigm in two different age groups, one younger than 2 years ( n = 4) and another more than 13 years of age ( n = 3). In addition, we obtained thresholds from one individual aged 23 years, three times during its lifetime. For computing audiograms, we presented test frequencies of between 0.5 and 12 kHz, covering the hearing range of the barn owl. Average thresholds in quiet were below 0 dB sound pressure level (SPL) for frequencies between 1 and 10 kHz. The lowest mean threshold was –12.6 dB SPL at 8 kHz. Thresholds were the highest at 12 kHz, with a mean of 31.7 dB SPL. Test frequency had a significant effect on auditory threshold but age group had no significant effect. There was no significant interaction between age group and test frequency. Repeated threshold estimates over 21 years from a single individual showed only a slight increase in thresholds. We discuss the auditory sensitivity of barn owls with respect to other species and suggest that birds, which generally show a remarkable capacity for regeneration of hair cells in the basilar papilla, are naturally protected from presbycusis.

As an essential means of resolving conflicts, aggression is expressed by both sexes but often at a higher level in males than in females. Recent studies suggest that cells in the ventrolateral part of the ventromedial hypothalamus (VMHvl) that express estrogen receptor-α (Esr1) and progesterone receptor are essential for male but not female mouse aggression. In contrast, here we show that VMHvlEsr1+ cells are indispensable for female aggression. This population was active when females attacked naturally. Inactivation of these cells reduced female aggression whereas their activation elicited attack. Additionally, we found that female VMHvl contains two anatomically distinguishable subdivisions that showed differential gene expression, projection and activation patterns after mating and fighting. These results support an essential role of the VMHvl in both male and female aggression and reveal the existence of two previously unappreciated subdivisions in the female VMHvl that are involved in distinct social behaviors.

The basal forebrain (BF) has long been implicated in attention, learning and memory, and recent studies have established a causal relationship between artificial BF activation and arousal. However, neural ensemble dynamics in the BF still remains unclear. Here, recording neural population activity in the BF and comparing it with simultaneously recorded cortical population under both anesthetized and unanesthetized conditions, we investigate the difference in the structure of spontaneous population activity between the BF and the auditory cortex (AC) in mice. The AC neuronal population show a skewed spike rate distribution, a higher proportion of short (≤80 ms) inter-spike intervals (ISIs) and a rich repertoire of rhythmic firing across frequencies. Although the distribution of spontaneous firing rate in the BF is also skewed, a proportion of short ISIs can be explained by a Poisson model at short time scales (≤20 ms) and spike count correlations are lower compared to AC cells, with optogenetically identified cholinergic cell pairs showing exceptionally higher correlations. Furthermore, a smaller fraction of BF neurons shows spike-field entrainment across frequencies: a subset of BF neurons fire rhythmically at slow (≤6 Hz) frequencies, with varied phase preferences to ongoing field potentials, in contrast to a consistent phase preference of AC populations. Firing of these slow rhythmic BF cells is correlated to a greater degree than other rhythmic BF cell pairs. Overall, the fundamental difference in the structure of population activity between the AC and BF is their temporal coordination, in particular their operational timescales. These results suggest that BF neurons slowly modulate downstream populations whereas cortical circuits transmit signals on multiple timescales. Thus, the characterization of the neural ensemble dynamics in the BF provides further insight into the neural mechanisms, by which brain states are regulated.

Dyslexia is a learning disability characterized by difficulty learning to read and write. The underlying biological and genetic etiology remains poorly understood. One candidate gene, dyslexia susceptibility 1 candidate 1 (DYX1C1), has been shown to be associated with deficits in short-term memory in dyslexic populations. The purpose of the current study was to examine the behavioral phenotype of a mouse model with a homozygous conditional (forebrain) knockout of the rodent homolog Dyx1c1. Twelve Dyx1c1 conditional homozygous knockouts, 7 Dyx1c1 conditional heterozygous knockouts and 6 wild-type controls were behaviorally assessed. Mice with the homozygous Dyx1c1 knockout showed deficits on memory and learning, but not on auditory or motor tasks. These findings affirm existing evidence that DYX1C1 may play an underlying role in the development of neural systems important to learning and memory, and disruption of this function could contribute to the learning deficits seen in individuals with dyslexia.

Hypoxic-ischemic (HI) brain injury is recognized as a significant problem in the perinatal period, contributing to life-long language-learning and other cognitive impairments. Central auditory processing deficits are common in infants with hypoxic-ischemic encephalopathy and have been shown to predict language learning deficits in other at risk infant populations. Inter-alpha inhibitor proteins (IAIPs) are a family of structurally related plasma proteins that modulate the systemic inflammatory response to infection and have been shown to attenuate cell death and improve learning outcomes after neonatal brain injury in rats. Here, we show that systemic administration of IAIPs during the early HI injury cascade ameliorates complex auditory discrimination deficits as compared to untreated HI injured subjects, despite reductions in brain weight. These findings have significant clinical implications for improving central auditory processing deficits linked to language learning in neonates with HI related brain injury.

Animal models are widely used to examine the neurophysiological basis of human pitch perception, and it is therefore important to understand the similarities and differences in pitch processing across species. Pitch discrimination performance is usually measured using two-alternative forced choice (2AFC) procedures in humans and go/no-go tasks in animals, potentially confounding human-to-animal comparisons. We have previously shown that pitch discrimination thresholds of ferrets on a 2AFC task are markedly poorer than those reported for go/no-go tasks in other non-human species (Walker et al ., 2009). To better compare the pitch discrimination performance of ferret with other species, here we measure pitch change detection thresholds of ferrets and humans on a common, appetitive go/no-go task design. We found that ferrets’ pitch thresholds were ~10 times larger than that of humans on the go/no-go task, and were within the range of thresholds reported in other non-human species. Interestingly, ferrets’ thresholds were 100 times larger than human thresholds on a 2AFC pitch discrimination task using the same stimuli. These results emphasize that sensory discrimination thresholds can differ across tasks, particularly for non-human animals. Performance on our go/no-go task is likely to reflect different neurobiological processes than that on our 2AFC task, as the former required the subjects only to detect a pitch change while the latter required them to label the direction of the pitch change. ABBREVIATIONS 2AFC 2-Alternative Forced Choice F0 Fundamental Frequency HIGHLIGHTS Pitch discrimination thresholds of ferrets were 10 times larger than those of humans on a go/no-go task Ferrets’ pitch thresholds are similar to those reported for a range of other mammals Pitch thresholds of ferrets, but not humans, were drastically better on the go/no-go task than a 2AFC task using the same stimuli

The cortex represents information across widely varying timescales. For instance, sensory cortex encodes stimuli that fluctuate over few tens of milliseconds, whereas in association cortex behavioural choices can require the maintenance of information over seconds. However, it remains poorly understood whether diverse timescales result mostly from features intrinsic to individual neurons or from neuronal population activity. This question remains unanswered, because the timescales of coding in populations of neurons have not been studied extensively, and population codes have not been compared systematically across cortical regions. Here we show that population codes can be essential to achieve long coding timescales. Furthermore, we find that the properties of population codes differ between sensory and association cortices. We compared coding for sensory stimuli and behavioural choices in auditory cortex and posterior parietal cortex as mice performed a sound localization task. Auditory stimulus information was stronger in auditory cortex than in posterior parietal cortex, and both regions contained choice information. Although auditory cortex and posterior parietal cortex coded information by tiling in time neurons that were transiently informative for approximately 200 milliseconds, the areas had major differences in functional coupling between neurons, measured as activity correlations that could not be explained by task events. Coupling among posterior parietal cortex neurons was strong and extended over long time lags, whereas coupling among auditory cortex neurons was weak and short-lived. Stronger coupling in posterior parietal cortex led to a population code with long timescales and a representation of choice that remained consistent for approximately 1 second. In contrast, auditory cortex had a code with rapid fluctuations in stimulus and choice information over hundreds of milliseconds. Our results reveal that population codes differ across cortex and that coupling is a variable property of cortical populations that affects the timescale of information coding and the accuracy of behaviour.

In childhood, partial hearing loss can produce prolonged deficits in speech perception and temporal processing. However, early therapeutic interventions targeting temporal processing may improve later speech-related outcomes. Gap detection is a measure of auditory temporal resolution that relies on the auditory cortex (ACx), and early auditory deprivation alters intrinsic and synaptic properties in the ACx. Thus, early deprivation should induce deficits in gap detection, which should be reflected in ACx gap sensitivity. We tested whether earplugging-induced, early transient auditory deprivation in male and female Mongolian gerbils caused correlated deficits in behavioral and cortical gap detection, and whether these could be rescued by a novel therapeutic approach: brief exposure to gaps in background noise. Two weeks after earplug removal, animals that had been earplugged from hearing onset throughout auditory critical periods displayed impaired behavioral gap detection thresholds (GDTs), but this deficit was fully reversed by three 1 h sessions of exposure to gaps in noise. In parallel, after earplugging, cortical GDTs increased because fewer cells were sensitive to short gaps, and gap exposure normalized this pattern. Furthermore, in deprived animals, both first-spike latency and first-spike latency jitter increased, while spontaneous and evoked firing rates decreased, suggesting that deprivation causes a wider range of perceptual problems than measured here. These cortical changes all returned to control levels after gap exposure. Thus, brief stimulus exposure, perhaps in a salient context such as the unfamiliar placement into a testing apparatus, rescued impaired gap detection and may have potential as a remediation tool for general auditory processing deficits.SIGNIFICANCE STATEMENT Hearing loss in early childhood leads to impairments in auditory perception and language processing that can last well beyond the restoration of hearing sensitivity. Perceptual deficits can be improved by training, or by acoustic enrichment in animal models, but both approaches involve extended time and effort. Here, we used a novel remediation technique, brief periods of auditory stimulus exposure, to fully remediate cortical and perceptual deficits in gap detection induced by early transient hearing loss. This technique also improved multiple cortical response properties. Rescue by this efficient exposure regime may have potential as a therapeutic tool to remediate general auditory processing deficits in children with perceptual challenges arising from early hearing loss.