Behavioral Neuroscience publications

Interpersonal coordination is fundamental to social evolution. We investigate its phenomenology and neural underpinnings in humans and macaques, examining the behavioral adaptations required for mutual coordination during motor interactions and the extent to which the underlying brain mechanisms are shared across species. Using a common interpersonal coordination paradigm, we conducted functional magnetic resonance imaging (fMRI) in humans and intracranial local field potential (LFP) recordings in macaques. Despite between-species behavioral discrepancies, both monkeys and humans coordinate through adjustments that proved to be based on proactive adaptation of motor planning and execution. Evidence from fMRI and time-resolved decoding analysis of LFPs converged to show modulation of premotor brain activity associated with interpersonal coordination and its effectiveness. Moreover, a dynamic sequential coding emerged, whereby the action context is represented early during planning, and coordination features near movement onset. Our findings reveal an evolutionarily conserved cortical architecture across primates that supports cooperative motor behavior.

Impulsivity is a core pathological feature of various psychiatric disorders including obsessive‐compulsive disorder, attention‐deficit/hyperactivity disorder, and schizophrenia, which is conceptualized as dysregulated motivational and inhibitory processes. However, the underlying neural mechanism is poorly known. Using an olfactory cued Go/No‐Go task, this work finds increased false alarm rate, shortened licking onset latency, elevated licking frequency and reduced inter‐trial consistency in mice treated by the NMDAR antagonist (MK‐801). Fiber optic recordings reveal MK‐801 enhanced cue‐evoked neuronal responses in the olfactory bulb (OB), orbitofrontal cortex (OFC), ventral tegmental area (VTA), and nucleus accumbens (NAc), while reducing reward‐predictive cue selectivity and increasing NAc dopamine release. Additionally, in vivo electrophysiological recordings demonstrate that theta oscillation power in the NAc and its coherence with OB, OFC, and VTA are also amplified. MK‐801 treatment enhances the correlation between firing rates of NAc neurons and cue, decreases the association with reward, strengthens the correlation with licking and increases the probability of firing peak preceding lick onset. Furthermore, this work confirms that the application of the trace amine‐associated receptor 1 agonist SEP‐363856 could correct the abnormal responses of NAc neurons and behavioral deficits. These findings elucidate the neural basis of impulsivity and support the potential therapeutic effect of SEP.

Atypical sensory processing, particularly in the auditory domain, is one of the most common and quality-of-life affecting symptoms seen in autism spectrum disorders (ASD). Fragile X Syndrome (FXS) is a leading inherited cause of ASD and a majority of FXS individuals present with auditory processing alterations. While auditory hypersensitivity is a common phenotype observed in FXS and Fmr1 knockout (KO) rodent models, it is important to consider other auditory coding impairments that could contribute to sound processing difficulties and disrupted language comprehension in FXS. We have shown previously that a Fmr1 KO rat model of FXS exhibits heightened sound sensitivity that coincided with abnormal perceptual integration of stimulus bandwidth, indicative of altered spectral processing. Frequency discrimination is a fundamental aspect of sound encoding that is important for a range of auditory processes, such as source segregation and speech comprehension, and disrupted frequency coding could thus contribute to a range of auditory issues in FXS and ASD. Here we explicitly characterized spectral processing deficits in male Fmr1 KO rats using an operant conditioning tone discrimination assay and in vivo electrophysiological recordings from the auditory cortex and inferior colliculus. We found that Fmr1 KO rats exhibited poorer frequency resolution, which corresponded with neuronal hyperactivity and broader frequency tuning in auditory cortical but not collicular neurons. Using an experimentally informed population model, we show that these cortical physiological differences can recapitulate the observed behavior discrimination deficits, with decoder performance being tightly linked to differences in cortical tuning width and signal-to-noise ratios. Together, these findings indicate that cortical hyperexcitability in Fmr1 KO rats may act to preserve signal-to-noise ratios and signal detection threshold at the expense of sound sensitivity and fine feature discrimination, highlighting a potential mechanistic locus for a range of auditory behavioral phenotypes in FXS.

Noise exposure is one of the most common causes of hearing loss and hyperacusis. Studies have shown that noise exposure can induce a cortical gain to compensate for reduced input of the cochlea, which may contribute to the increased sound sensitivity. However, many people with hyperacusis have no measurable cochlear lesion after being exposed to loud sound. In this experiment, we studied the neurological alterations in the cortical and subcortical areas following a prolonged moderate level of noise exposure (84 dB SPL, 8 h/day for 4 weeks) in the laboratory mice. The cochlear function was monitored by auditory brainstem responses (ABRs). The behavioral auditory sensitivity and temporal processing were evaluated using the acoustic startle response (ASR) and gap‐induced prepulse inhibition (gap‐PPI). The central auditory functions were determined by electrophysiological recordings of the inferior colliculus (IC) and the auditory cortex (AC). Our results showed that although there was no significant difference in the ABR thresholds, the noise group showed enhanced ASR and gap‐PPI compared to the control group. Increased neural activity in both the IC and the AC was recorded in the noise‐exposed mice compared to the control group, suggesting a central gain in both the subcortical and cortical regions. The current source density (CSD) analysis of the AC response revealed an increased columnar excitation and reduced corticocortical projection in the noise group, different from the central gain model of noise‐induced hearing loss. Our results suggest that chronic “nondestructive” noise can increase the gain of the central auditory system by altering the balance of auditory thalamocortical and intracortical inputs, which may contribute to the increased sound sensitivity in people with normal hearing.

Tinnitus has been identified as a potential contributor to anxiety. Thalamo-cortical pathway plays a crucial role in the transmission of auditory and emotional information, but its casual link to tinnitus-associated anxiety remains unclear. In this study, we explore the neural activities in the thalamus and cortex of the sodium salicylate (NaSal)-treated mice, which exhibit both hyperacusis and anxiety-like behaviors. We find an increase in gamma band oscillations (GBO) in both auditory cortex (AC) and prefrontal cortex (PFC), as well as phase-locking between cortical GBO and thalamic neural activity. These changes are attributable to a suppression of GABAergic neuron activity in thalamic reticular nucleus (TRN), and optogenetic activation of TRN reduces NaSal-induced hyperacusis and anxiety-like behaviors. The elevation of endocannabinoid (eCB)/ cannabinoid receptor 1 (CB1R) transmission in TRN contributes to the NaSal-induced abnormalities. Our results highlight the regulative role of TRN in the auditory and limbic thalamic-cortical pathways.

The hearing abilities of mammals are impacted by factors such as social cues, habitat, and physical characteristics. Despite being used commonly to study social behaviors, hearing of the monogamous prairie vole (Microtus ochrogaster) has never been characterized. In this study, anatomical features are measured and auditory brainstem responses (ABRs) are used to measure auditory capabilities of prairie voles, characterizing monaural and binaural hearing and hearing range. Sexually naive male and female voles were measured to characterize differences due to sex. It was found that prairie voles show a hearing range with greatest sensitivity between 8 and 32 kHz, binaural hearing across interaural time difference ranges appropriate for their head sizes. No differences are shown between the sexes in binaural hearing or hearing range (except at 1 kHz), however, female voles have increased amplitude of peripheral ABR waves I and II and longer latency of waves III and IV compared to males. The results confirm that prairie voles have a broad hearing range, binaural hearing consistent with rodents of similar size, and differences in amplitudes and thresholds of monaural physiological measures between the sexes. These data further highlight the necessity to understand sex-specific differences in neural processing that may underly variability in responses between sexes.

The auditory steady-state response (ASSR) is a cortical oscillation induced by trains of 40 Hz acoustic stimuli. While the ASSR has been widely used in clinic measurement, the underlying neural mechanism remains poorly understood. In this study, we investigated the contribution of different stages of auditory thalamocortical pathwaymedial geniculate body (MGB), thalamic reticular nucleus (TRN), and auditory cortex (AC)to the generation and regulation of 40 Hz ASSR in C57BL/6 mice of both sexes. We found that the neural response synchronizing to 40 Hz sound stimuli was most prominent in the GABAergic neurons in the granular layer of AC and the ventral division of MGB (MGBv), which were regulated by optogenetic manipulation of TRN neurons. Behavioral experiments confirmed that disrupting TRN activity has a detrimental effect on the ability of mice to discriminate 40 Hz sounds. These findings revealed a thalamocortical mechanism helpful to interpret the results of clinical ASSR examinations. Significance Statement Our study contributes to clarifying the thalamocortical mechanisms underlying the generation and regulation of the auditory steady-state response (ASSR), which is commonly used in both clinical and neuroscience research to assess the integrity of auditory function. Combining a series of electrophysiological and optogenetic experiments, we demonstrate that the generation of cortical ASSR is dependent on the lemniscal thalamocortical projections originating from the ventral division of medial geniculate body to the GABAergic interneurons in the granule layer of the auditory cortex. Furthermore, the thalamocortical process for ASSR is strictly regulated by the activity of thalamic reticular nucleus (TRN) neurons. Behavioral experiments confirmed that dysfunction of TRN would cause a disruption of mice's behavioral performance in the auditory discrimination task.

Foraging on nocturnally migrating birds is one of the most challenging foraging tasks in the animal kingdom. Only three bat species (e.g., Ia io) known to date can prey on migratory birds. However, how these bats have exploited this challenging dietary niche remains unknown. Here, we demonstrate that I. io hunts at the altitude of migrating birds during the bird migration season. The foraging I. io exhibited high flight altitudes (up to 4945 m above sea level) and high flight speeds (up to 143.7 km h-1). I. io in flight can actively prey on birds in the night sky via echolocation cues. Genes associated with DNA damage repair, hypoxia adaptation, biting and mastication, and digestion and metabolism have evolved to adapt to this species' avivorous habits. Our results suggest that the evolution of behavioral innovation and genomic novelty are associated with the exploitation of challenging dietary opportunities.

Aims We aimed to find where and how noise‐induced cochlear hearing loss affects the central nervous system during the early state and identify the neural substrate for aberrant patterns that mediating noise‐related anxiety−/depression‐ like behaviors. Methods Broad band noise with 122 dB for 2 hours was conducted to induce hearing loss. We defined 0 day (N0D) and 10 days (N10D) post noise as the acute and sub‐acute period. Behavioral tests (Open field test and light/dark test) and resting‐state fMRI were computed to evaluate emotional conditions and aberrant neural activity. Functional connectivity analysis using the anterior cingulate cortex as a seed was computed to reveal the spatial distribution beyond auditory network during both periods. Results Anxiety−/depression‐like behaviors were found in rats with noise exposure. Between‐group analysis revealed that N0D rats displayed widespread reductions in functional connectivity, spanning primary somatosensory cortex, medial geniculate body, inferior colliculus, cingulate cortex, cerebellar lobule comparing with N10D rats and a similar pattern was also occurred in comparison with the control group. Conclusion Taken together, an “acoustic‐causing” network accounting for distress and gating of noise exposure related anxiety/depression was proposed.

Dominant neuroanatomical models hold that humans regulate their movements via loop-like cortico-subcortical networks, which include the subthalamic nucleus (STN), motor thalamus, and sensorimotor cortex (SMC). Inhibitory commands across these networks are purportedly sent via transient, burst-like signals in the β frequency (15–29 Hz). However, since human depth-recording studies are typically limited to one recording site, direct evidence for this proposition is hitherto lacking. Here, we present simultaneous multi-site recordings from SMC and either STN or motor thalamus in humans performing the stop-signal task. In line with their purported function as inhibitory signals, subcortical β-bursts were increased on successful stop-trials. STN bursts in particular were followed within 50 ms by increased β-bursting over SMC. Moreover, between-site comparisons (including in a patient with simultaneous recordings from SMC, thalamus, and STN) confirmed that β-bursts in STN temporally precede thalamic β-bursts. This highly unique set of recordings provides empirical evidence for the role of β-bursts in conveying inhibitory commands along long-proposed cortico-subcortical networks underlying movement regulation in humans.

The temporal frequency of sensory stimulation is a decisive factor in the plasticity of perceptual detection thresholds. However, surprisingly little is known about how distinct temporal parameters of sensory input differentially recruit activity of neuronal circuits in sensory cortices. Here we demonstrate that brief repetitive visual stimulation induces long-term plasticity of visual responses revealed 24 h after stimulation and that the location and generalization of visual response plasticity is determined by the temporal frequency of the visual stimulation. Brief repetitive low-frequency stimulation (2 Hz) is sufficient to induce a visual response potentiation that is expressed exclusively in visual cortex layer 4 and in response to a familiar stimulus. In contrast, brief, repetitive high-frequency stimulation (HFS, 20 Hz) is sufficient to induce a visual response potentiation that is expressed in all cortical layers and transfers to novel stimuli. HFS induces a long-term suppression of the activity of fast-spiking interneurons and primes ongoing gamma oscillatory rhythms for phase reset by subsequent visual stimulation. This novel form of generalized visual response enhancement induced by HFS is paralleled by an increase in visual acuity, measured as improved performance in a visual detection task.

Sensorineural hearing loss (SNHL) has been demonstrated in many clinical reports as a risk factor that promotes the development of cognitive impairment. However, the underlying neurological mechanisms are not clear. Noise exposure is one of the most common causes of SNHL. Although noise exposure causes relatively less damage to general health as compared with other methods for creating hearing loss (such as ototoxicity), it does impair cognitive function. Many studies have shown that the noise-induced cognitive impairment occur via the oxidative stress induced by the noise. In those studies, the effects of the noise-induced hearing loss induced (NIHL) were not addressed. Previously, we have demonstrated in the CBA/CaJ mouse model that oxidative stress was transient after a brief noise exposure, but the NIHL was permanent. In addition, NIHL was followed by a declined cognitive function and decreased hippocampal neurogenesis that were developed long after the oxidative stress disappeared. Therefore, NIHL can cause cognitive impairment independent of its stress effect and can serve as a model to investigate the relationship between hearing loss and the development of cognitive impairment. In the present study, we further demonstrated that the oxidative stress produced by the brief noise exposure did not damage the stem cell bank of hippocampus that was evaluated shortly after the noise exposure. In addition to the reduction in the rate of cell proliferation in hippocampus that was found previously, we found that the NIHL significantly reduced the promoting effect of learning activity on various stages of hippocampal neurogenesis, accompanied by the reduction in learning-induced expression of immediate early genes (IEGs) in hippocampus. Since the MWM-tested spatial function does not directly require auditory input, the results provide evidence for the maintenance role of auditory input on the cognitive function; the reduction of IEG expression that is required in memory-formation may be the initial step in blocking the effect of learning activity on neurogenesis in subjects with NIHL.

Increased acoustic startle responses (ASR), which represent reduced uncomfortable loudness level in humans, have been reported in middle-aged C57BL/6J mice with sensorineural hearing loss. Although neural plasticity changes in the central auditory system after the peripheral lesions were suggested to underlie this phenomenon, the neurological cause of exaggerated ASR is still not clear. In this study, the local field potentials and firing rates of the caudal pontine reticular nucleus (PnC), which plays a major role in the ASR pathway, were recorded in 2-month- and 6-month-old C57BL/6 J mice. Consistent with our previous studies, the amplitude of ASR increased, and the threshold of ASR decreased in the 6-month-old mice after developing 20–40 dB hearing loss. The PnC response induced by high-frequency stimuli (>20 kHz) decreased in the 6-month group, whereas the PnC response induced by low-frequency stimuli (<12 kHz) showed a significant increase in the 6-month group compared to the 2-month group. The enhancement of PnC response is similar to the ASR increase found in the 6-month-old C57 mice. Our results suggest that the high-frequency hearing loss caused an increase in PnC sensitivity in the C57 mice which may enhance ASRs.

Accurate and adaptive encoding of complex, dynamic visual information is critical for the survival of many animals. Studies across a range of taxa have investigated behavioral and neuronal responses to objects that represent a threat, such as a looming object approaching along a direct collision course. By investigating neural mechanisms of avoidance behaviors through recording multineuronal activity, it is possible to better understand how complex visual information is represented in circuits that ultimately drive behaviors. We used multichannel electrodes to record from the well-studied locust nervous system to explore how object motion is reflected in activity of correlated neural activity. We presented locusts (Locusta migratoria) with objects that moved along one of 11 unique trajectories and recorded from descending interneurons within the ventral nerve cord. Spike sorting resulted in 405 discriminated units across 20 locusts and we found that 75% of the units responded to some form of object motion. Dimensionality reduction through principal component (PCA) and dynamic factor (DFA) analyses revealed population vector responses within individuals and common firing trends across the pool of discriminated units, respectively. Population vector composition (PCA) varied with the stimulus and common trends (DFA) showed unique tuning related to changes in the visual size and trajectory of the object through time. These findings demonstrate that this well-described collision detection system is more complex than previously envisioned and will drive future experiments to explore fundamental principles of how visual information is processed through context-dependent dynamic ensembles of neurons to initiate and control complex behavior.

The addition of tactile and proprioceptive feedback to neuroprosthetic limbs is expected to significantly improve the control of these devices. Intracortical microstimulation (ICMS) of somatosensory cortex is a promising method of delivering this sensory feedback. To date, the main focus of somatosensory ICMS studies has been to deliver discriminable signals, corresponding to varying intensity, to a single location in cortex. However, multiple independent and simultaneous streams of sensory information will need to be encoded by ICMS to provide functionally relevant feedback for a neuroprosthetic limb (e.g., encoding contact events and pressure on multiple digits). In this study, we evaluated the ability of an awake, behaving non-human primate (Macaca mulatta) to discriminate ICMS stimuli delivered on multiple electrodes spaced within somatosensory cortex. We delivered serial stimulation on single electrodes to evaluate the discriminability of sensations corresponding to ICMS of distinct cortical locations. Additionally, we delivered trains of multichannel stimulation, derived from a tactile sensor, synchronously across multiple electrodes. Our results indicate that discrimination of multiple ICMS stimuli is a challenging task, but that discriminable sensory percepts can be elicited by both single and multichannel ICMS on electrodes spaced within somatosensory cortex.

Tonotopic map plasticity in the adult auditory cortex (AC) is a well established and oft-cited measure of auditory associative learning in classical conditioning paradigms. However, its necessity as an enduring memory trace has been debated, especially given a recent finding that the areal expansion of core AC tuned to a newly relevant frequency range may arise only transiently to support auditory learning. This has been reinforced by an ethological paradigm showing that map expansion is not observed for ultrasonic vocalizations (USVs) or for ultrasound frequencies in postweaning dams for whom USVs emitted by pups acquire behavioral relevance. However, whether transient expansion occurs during maternal experience is not known, and could help to reveal the generality of cortical map expansion as a correlate for auditory learning. We thus mapped the auditory cortices of maternal mice at postnatal time points surrounding the peak in pup USV emission, but found no evidence of frequency map expansion for the behaviorally relevant high ultrasound range in AC. Instead, regions tuned to low frequencies outside of the ultrasound range show progressively greater suppression of activity in response to the playback of ultrasounds or pup USVs for maternally experienced animals assessed at their pups’ postnatal day 9 (P9) to P10, or postweaning. This provides new evidence for a lateral-band suppression mechanism elicited by behaviorally meaningful USVs, likely enhancing their population-level signal-to-noise ratio. These results demonstrate that tonotopic map enlargement has limits as a construct for conceptualizing how experience leaves neural memory traces within sensory cortex in the context of ethological auditory learning.

Hearing loss has been associated with cognitive decline in the elderly and is considered to be an independent risk factor for dementia. One of the most common causes for acquired sensorineural hearing loss is exposure to excessive noise, which has been found to impair learning ability and cognitive performance in human subjects and animal models. Noise exposure has also been found to depress neurogenesis in the hippocampus. However, the effect is mainly attributed to the oxidant stress of noise on the cognitive brain. In the present study, young adult CBA/CAJ mice (between 1.5 and 2 months of age) were briefly exposed a high sound level to produce moderate-to-severe hearing loss. In both the blood and hippocampus, only transient oxidative stress was observed after noise exposure. However, a deficit in spatial learning/memory was revealed 3 months after noise exposure. Moreover, the deficit was correlated with the degree of hearing loss and was associated with a decrease in neurogenesis in the hippocampus. We believe that the observed effects were likely due to hearing loss rather than the initial oxidant stress, which only lasted for a short period of time.

While the timing of neuronal activity in the olfactory bulb (OB) relative to sniffing has been the object of many studies, the behavioral relevance of timing information generated by patterned activation within the bulbar response has not been explored. Here we show, using sniff-triggered, dynamic, 2-D, optogenetic stimulation of mitral/tufted cells, that virtual odors that differ by as little as 13 ms are distinguishable by mice. Further, mice are capable of discriminating a virtual odor movie based on an optically imaged OB odor response versus the same virtual odor devoid of temporal dynamics-independently of the sniff-phase. Together with studies showing the behavioral relevance of graded glomerular responses and the response timing relative to odor sampling, these results imply that the mammalian olfactory system is capable of very high transient information transmission rates.

Animal models of tinnitus allow us to study the relationship between changes in neural activity and the tinnitus percept. Here, guinea pigs were subjected to unilateral noise trauma and tested behaviourally for tinnitus 8 weeks later. By comparing animals with tinnitus with those without, all of which were noise‐exposed, we were able to identify changes unique to the tinnitus group. Three physiological markers known to change following noise exposure were examined: spontaneous firing rates ( SFR s) and burst firing in the inferior colliculus ( IC ), evoked auditory brainstem responses ( ABR s), and the number of neurons in the cochlear nucleus containing nitric oxide synthase ( NOS ). We obtained behavioural evidence of tinnitus in 12 of 16 (75%) animals. Both SFR s and incidences of burst firing were elevated in the IC of all noise‐exposed animals, but there were no differences between tinnitus and no‐tinnitus animals. There were significant decreases in ipsilateral ABR latencies in tinnitus animals, contrary to what might be expected with a small hearing loss. Furthermore, there was an ipsilateral–contralateral asymmetry in NOS staining in the ventral cochlear nucleus ( VCN ) that was only apparent in tinnitus animals. Tinnitus animals had a significantly greater number of NOS ‐containing neurons on the noise‐exposed side, whereas no‐tinnitus animals did not. These data suggest that measuring NOS in the VCN and recording ABR s supplement behavioural methods for confirming tinnitus in animals, and that nitric oxide is involved in plastic neural changes associated with tinnitus.

Previous studies have shown that sodium salicylate (SS) activates not only central auditory structures, but also nonauditory regions associated with emotion and memory. To identify electrophysiological changes in the nonauditory regions, we recorded sound-evoked local field potentials and multiunit discharges from the striatum, amygdala, hippocampus, and cingulate cortex after SS-treatment. The SS-treatment produced behavioral evidence of tinnitus and hyperacusis. Physiologically, the treatment significantly enhanced sound-evoked neural activity in the striatum, amygdala, and hippocampus, but not in the cingulate. The enhanced sound evoked response could be linked to the hyperacusis-like behavior. Further analysis showed that the enhancement of sound-evoked activity occurred predominantly at the midfrequencies, likely reflecting shifts of neurons towards the midfrequency range after SS-treatment as observed in our previous studies in the auditory cortex and amygdala. The increased number of midfrequency neurons would lead to a relative higher number of total spontaneous discharges in the midfrequency region, even though the mean discharge rate of each neuron may not increase. The tonotopical overactivity in the midfrequency region in quiet may potentially lead to tonal sensation of midfrequency (the tinnitus). The neural changes in the amygdala and hippocampus may also contribute to the negative effect that patients associate with their tinnitus.