Behavioral Neuroscience publications

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by CGG trinucleotide repeat expansion in the fragile X messenger ribonucleoprotein 1 (FMR1) gene and the resulting loss of fragile X messenger ribonucleoprotein (FMRP). Gene therapy using recombinant adeno-associated virus (AAV) to restore FMRP expression, particularly in the brain, is a promising therapeutic strategy targeting the underlying cause of FXS. We examined the impact of AAV serotype 9 (AAV9)-mediated expression of a brain-abundant human FMRP isoform (isoform 7) driven by a fragment of the human FMR1 promoter on circuit and behavioral dysfunctions in the male Fmr1 knockout (KO) mouse, FXS model. Following intracerebroventricular (i.c.v.) injection of AAV9-NG276 into neonatal KO mice at a low (1e11 vg/animal) or high (3e11 vg/animal) dose, we assessed cortical phenotypes using electroencephalography (EEG) recordings and behavioral testing. High-dose AAV9-NG276 normalized baseline gamma power, improved sound-evoked responses, and reduced background neural activity. Analysis of behavioral deficits in adult KO mice showed that high-dose neonatal AAV9-NG276 delivery normalized exploratory behaviors, social preference, and probabilistic reversal learning. Thus, early AAV-mediated delivery of human FMR1 isoform 7 ameliorates cortical dysfunction and behavioral deficits in a murine FXS model and suggests that widespread cortical biodistribution is required for therapeutic benefit.

Purpose: In anesthesia research and clinical practice, the level of consciousness is often assessed by stimulating subjects and observing their responses. It is possible that such stimulation alters the very state of consciousness being assessed. Whether this phenomenon is accompanied by specific cortical activities remains unknown. Here, we tested the effects of behavioral assessments on neuronal activity in the rat primary auditory cortex (A1) and perirhinal cortex (PrC). Methods: Neuronal spiking activity was recorded from microwire arrays targeting A1 and/or PrC in rats (n = 9), whilst presenting 40 Hz click-trains and gradually increasing infusion rates of propofol, remifentanil, ketamine or dexmedetomidine. We assessed righting reflex, pain withdrawal, whisking reflex, and corneal reflex every 12 minutes (every 360 auditory trials). We searched for significant changes in baseline firing rate and stimulus-evoked activities (where present) due to the behavioral assessments, by comparing 4 min intervals before and after the behavioral tests. Results: Out of 1004 units in 20 sessions, we found significantly elevated activity (p < 0.01) following behavioral tests in 32% and 20% of A1 auditory-responsive units and 8.6% and 5.3% of auditory-unresponsive units under propofol and dexmedetomidine, respectively, but not under remifentanil or ketamine. A higher proportion of units modulated their firing following behavioral tests in A1 compared to PrC, with median gains ranging from +0.23 to +1.06, depending on the specific response feature. Conclusion: Behavioral testing increases ongoing firing rate and responses to sounds in some cortical neurons. This increase is more prevalent in A1 than in PrC, mirroring clinical observations that patients exhibit basic responses under sedation, while complex processing, such as memory encoding, is impaired. The degree of neuronal modulation due to behavioral testing varies between anesthetic agents, mirroring their clinical phenotypes.

Objective Traumatic brain injury (TBI) significantly reduces the quality of life for millions of survivors worldwide, causing persistent brain tissue damage and cognitive impairments, with no established therapeutic interventions currently available. Slow‐wave activity, a hallmark of deep sleep, has been implicated in recovery after TBI, but pharmacological approaches to enhance it lack specificity and scalability, complicating efforts to identify slow‐wave activity as a direct mechanistic contributor and severely limiting clinical translation. Methods To overcome these limitations, we developed a preclinical closed‐loop auditory stimulation (CLAS) paradigm that targets sleep's slow waves, enabling highly specific and temporally precise enhancement of slow‐wave activity. Therefore, we delivered 30‐ms sound triggers targeting the up‐phase of real‐time detected slow‐waves (upCLAS: TBI n = 8), or no sound stimulation (mockCLAS: non‐TBI n = 8, TBI n = 7) during sleep to healthy controls (non‐TBI) or brain injured (TBI) rats. Concomitantly, we assessed the ability of upCLAS‐enhanced sleep to counteract brain tissue damage (primary outcome) and symptomatic sequelae (secondary outcome) of TBI. Results Bayesian analysis revealed that sound‐mediated slow‐wave activity enhancement: (1) reduces diffuse axonal injury, with TBI mockCLAS posterior estimates falling outside the 95% confidence intervals of both other groups, whereas the posterior distributions of TBI upCLAS and non‐TBI groups largely overlapped (~13% posterior differences >0), consistent with a negligible effect size between groups; (2) decreases demyelination, with approximately 97% posterior differences >0 between TBI mockCLAS and TBI upCLAS groups, compared to approximately 60% between non‐TBI and TBI upCLAS groups; and (3) preserves cognitive ability, with recognition indexes in the novel object recognition test significantly above chance level in non‐TBI (* p = 0.031) and TBI upCLAS (* p = 0.026) groups, in contrast to mockCLAS‐treated TBI rats ( p = 0.156), presenting pronounced cognitive deficit. Furthermore, microglial response to brain injury was increased by deep sleep enhancement, with reduced ionized calcium‐binding adaptor molecule 1+ area coverage in TBI upCLAS rats (* p = 0.0445) compared to non‐TBI ones. Interpretation These results unambiguously demonstrate slow‐wave activity enhancement confers robust disease modification following TBI while overcoming major limitations of other preclinical approaches. Our findings constitute proof‐of‐concept that boosted sleep intensity mitigates histopathological and cognitive sequelae of brain trauma, suggesting that a clinically relevant, nonobtrusive, sleep‐based therapy may represent a novel therapeutic intervention for TBI survivors. ANN NEUROL 2026;100:242–254

Hearing is the largest modifiable mid-life risk factor for Alzheimer's disease (AD), yet its link to dementia remains unclear. We identified a neurophysiological biomarker of AD risk using the non-invasive, rapidly acquired, and clinically translatable auditory brainstem response (ABR) in normal hearing knock-in rats (Swedish familial AD risk variant to Amyloid precursor protein, AppS; male and female). Human ABRs have been proposed as a biomarker for AD and related dementias. The novel metric reported here is derived from multidimensional parametric feature extraction on the distribution statistics of repeated single-trial ABR traces. We report accurate prediction of genetic risk for AD risk in young and aged rats: AppS separate clearly from healthy humanized (AppH) in sex- and age-dependent manners. Notably, auditory learning during young adulthood shifted the AppS ABR signature towards a healthy AppH-like state that maintained over time into older age. Altogether the findings support the utility of the ABR to track disease state, progression, and effects of intervention, and point to a central neural generator of auditory dysfunction related to AD risk. ABRs could provide a very early biomarker for detection of AD risk and used to test the synergy of auditory and cognitive functions in human dementia.

Our ability to generalize abstract rules to new situations is a cognitive hallmark, yet its neural basis is unclear. We identified a thalamocortical circuit essential for this process in mice. During a cross-modal rule transfer task, medial prefrontal cortex (mPFC) neurons encoded task rules across sensory modalities to enable generalization. Crucially, mediodorsal thalamus (MD) projections to mPFC were causally required: Inhibiting this pathway destabilized mPFC representations and impaired rule transfer, whereas enhancing it improved performance. Without MD input, mPFC recruited distinct populations for each task, losing cross-context stability. Direct mPFC excitation impaired generalization, underscoring the specificity of thalamic regulation. Thus, the MD stabilizes mPFC activity for flexible rule transfer—a mechanism with implications for cognitive disorders and artificial intelligence.

Age-related hearing loss (ARHL), or presbycusis, is one of the most prevalent sensory deficits in older adults and has been increasingly implicated in cognitive decline and dementia. This study characterizes ARHL in a rhesus macaque model by combining histological, physiological, and cognitive assessments. Aged macaques exhibited progressive cochlear degeneration, with marked outer hair cell loss at mid-to-high frequencies, elevated auditory thresholds, reduced distortion product otoacoustic emissions, and impaired auditory brainstem responses including amplitude reduction, latency prolongation, and diminished temporal precision. Despite modest reductions in inner hair cell ribbon synapse counts, hypertrophic changes were observed. These auditory deficits correlated with subtle impairments in visual working memory, as measured by a delayed match-to-sample task, underscoring a potential sensory-cognitive link. By capturing cross-domain aging markers in a translationally relevant primate model, this work lays a foundation for mechanistic studies and therapeutic interventions targeting both hearing and cognition in aging populations.

It is widely accepted that tinnitus arises from maladaptive neuroplasticity in the central auditory system, which compensates for reduced peripheral input; notably, the loss of inner hair cell (IHC) synapses is considered a key underlying factor. IHC synapses can immediately and permanently degenerate after noise exposure, independent of hair cell loss, whereas the cell bodies and central projections of cochlear neurons can survive for months to years, providing an extended therapeutic window for improving afferent input through synapse regeneration. Using NHPN-1010 (a combination of 2,4-disulfophenyl-N-tert-butylnitrone and N-acetylcysteine), we propose a delayed treatment strategy (≥ 4 weeks after trauma) for noise-induced tinnitus (NIT) in rats. NHPN-1010 enhanced gap-prepulse inhibition of acoustic startle responses-indicative of diminished tinnitus-like deficits-coupled with a concomitant upregulation of GABAergic inhibition in the dorsal cochlear nucleus, relative to vehicle alone (saline). Furthermore, NHPN-1010, compared to saline, led to increased wave-I amplitudes of auditory brainstem responses, the effect accompanied by a corresponding rise in the number of presynaptic ribbons in IHCs. Our findings suggest that NHPN-1010 plays a therapeutic role in NIT by promoting cochlear synaptogenesis and normalizing central auditory signaling.

Astrocytes control neural communications by influencing GABAergic transmission through uptake and synthesis of GABA. Impaired GABAergic signaling is thought to underlie cortical hyperexcitability in autism. Here we show that dysregulation of astrocyte GABA transport in Fragile X syndrome (FXS), a leading genetic cause of autism, contributes to circuit hyperexcitability. Human FXS astrocytes derived from patient-specific induced pluripotent stem cells and mouse Fmr1 knockout (KO) astrocytes display a significant increase in levels of GABA and GABA-synthesizing enzyme GAD65/67. Our astrocyte-specific Fmr1 KO (cKO) mouse model reveals reduced inhibitory connectivity and impaired cortical responses to sound. Abnormal GABA transport in cortical astrocytes contributes to impaired fidelity of temporal processing and abnormal behaviors in cKO mice. Blocking astrocyte GABA transport enables higher PV expression, improves EEG responses to frequency-modulated sound, and corrects aberrant exploratory behavior. Our findings suggest astrocyte GABA transport plays a key role in regulating cortical inhibition, and contributes to autism-associated phenotypes.

Background DFNB16, the second most common genetic cause of hearing loss, is caused by mutations of the STRC gene encoding stereocilin, a protein essential for the effective functioning of outer hair cells (OHCs) as cochlear amplifiers. Strc −/− mice, which lack stereocilin, display severe to profound deafness and constitute a relevant preclinical model for DFNB16. Methods Using Strc − / − mice, we developed a gene therapy strategy based on the use of dual AAV9‐PHP.eB vectors to deliver the full‐length Strc cDNA. Therapeutic efficacy was assessed by evaluating stereocilin expression, OHC bundle architecture, and their attachment to the tectorial membrane, together with functional recovery using distortion product otoacoustic emissions (DPOAEs), auditory brainstem responses (ABR) measurements and Go/No‐Go behavioral testing with psychometric analysis. Results Dual‐AAV–mediated Strc gene delivery restored stereocilin expression, OHC bundle architecture and their attachment to the tectorial membrane, leading to the recovery of cochlear amplification and hearing to near normal thresholds, as confirmed by distortion product otoacoustic emission (DPOAE) and auditory brainstem response measurements. Behavioural assessment showed that treated Strc −/− mice regained normal frequency discrimination, indicating a restoration of higher‐order auditory processing, up to 100 days post‐treatment. Conclusion These findings provide the first proof‐of‐principle that peripheral gene therapy can restore OHC function, cochlear amplification and central auditory perception in a DFNB16 model. Key points Dual AAV‐mediated gene delivery restored peripheral hearing in a DFNB16 preclinical mouse model. The same treatment also restored central auditory processing. AAV‐mediated gene therapy represents a promising curative strategy for DFNB16. These results reinforce the translational potential for treating human genetic deafness.

Although age-related hearing loss (ARHL) is the most common sensory loss in older adults, underlying mechanisms remain unclear. Recent genome-wide association studies (GWAS) linked variation in several genes with ARHL risk, including KLHDC7B , a gene of unknown function not previously linked to hearing. We demonstrate Klhdc7b is expressed exclusively in sensory hair cells in mouse cochlea. Utilizing two independent mouse knockout models ( Klhdc7b IMPC-/- and Klhdc7b Regn Δ/Δ ) we find that absence of Klhdc7b leads to severe early-onset, progressive hearing loss. Hair cells appear to develop normally, but outer hair cells are progressively lost from base-to-apex of the cochlea, a common pathology in ARHL. These results suggest KLHDC7B is required for maintenance rather than development, of auditory function. The validation in mouse of a human ARHL GWAS association suggests other novel candidates should be investigated. Our work provides two mouse models to study KLHDC7B function, and for development of therapeutic tools for ARHL.

Memory consolidation enables animals to draw on past experiences to guide future behavior. This process involves system- and synaptic-level changes and predominantly occurs during sleep. While hippocampal-cortical circuits are well studied in this context, the contributions of other systems, including dopaminergic circuits—key players in learning-related processes—remain poorly understood. Ventral tegmental area dopaminergic (VTA DA ) neurons are active during sleep and suggested to participate in memory consolidation processes; however, causal evidence for this is lacking. Using calcium-dependent fiber photometry, electrophysiology, and chemogenetic and optogenetic manipulations across learning paradigms, we explore the functions of VTA DA neuronal activity during sleep. We show that VTA DA activity during nonrapid eye movement sleep is experience dependent, is enhanced by motor skill and associative learning, facilitates motor skill memory consolidation, and exhibits a motor learning–dependent increase in temporal coordination with cortical spindle oscillations. Our findings uncover a previously unidentified function for VTA DA neurons in consolidating memories during sleep, advancing understanding of this central neuromodulator’s functions in regulating fundamental biological processes.

Noise-induced hearing loss (NIHL) is a primary contributor to tinnitus, involving mechanisms such as inflammatory damage, central sensitization, and auditory cortex remodeling. However, not all cases of tinnitus are accompanied by NIHL, and the precise relationship between the two remains incompletely understood. Phosphorylation/dephosphorylation, as a core mechanism for fine cellular regulation, influences neuronal excitability, immune responses, and disease development by modulating protein activity, signal transduction, and gene expression. We hypothesized that aberrant phosphorylation levels may alter auditory cortex neuron function, leading to pathological changes at the protein level. Leveraging auditory cortex tissue from a noise-induced tinnitus model, we systematically investigated the pathogenesis of tinnitus and its distinction from NIHL through integrated proteomic and phosphoproteomic analyses. Compared to animals with NIHL alone, the tinnitus model exhibited enhanced neuronal excitability, synaptic dysfunction, hyperactive energy metabolism, and weakened neuroprotection, with disordered membrane receptor function playing a critical role. Multi-omics analysis further revealed that tinnitus development primarily depends on phosphorylation-mediated post-translational modifications reshaping cellular function, rather than changes in protein abundance caused by alterations in gene transcription levels. Collectively, this study elucidates the physiological and cellular structural alterations in noise-induced tinnitus from the dimensions of protein expression and phosphorylation modification. It confirms that tinnitus leads to neural dysfunction through abnormal membrane receptor activity, and the characteristic proteins and phosphorylation sites identified offer novel therapeutic targets for modulating central hyperexcitability in tinnitus.

We describe here a mode of activity of neurons in auditory cortex of freely moving rats consisting of 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. This activity mode had important functional consequences to sound processing during task performance. We show that the slow firing rate modulations caused the ongoing activity just before sound presentations to be higher during task performance than during passive listening. Concurrently, during task performance, the responses to target stimuli were weaker but more informative about the task-relevant sounds. In a model, higher ongoing activity caused more synaptic depression of the cortico-cortical synapses, reducing the tendency of the network to produce population spikes and resulting in weaker but more informative responses to sounds.

Introduction The posterior tail of the striatum receives dense inputs from sensory regions of cortex and thalamus, as well as midbrain dopaminergic innervation, providing a neural substrate for associative sensory learning. Previously, we have demonstrated that developmental hearing loss is associated with aberrant physiological states in striatal medium spiny neurons (MSNs). Methods Here we directly investigated auditory associative learning impairments in the striatum of adult Mongolian gerbils that underwent transient developmental hearing loss or sham hearing loss during the critical period of auditory development. We used electrophysiology to reveal significant changes to neuronal population responses in vivo and intrinsic and synaptic properties to medium spiny neurons in vitro as animals learned an appetitive “Go/No-Go” auditory discrimination task. For in vivo experiments a 64-channel electrode was implanted in the auditory region of the posterior tail of the striatum and neuronal recordings were carried out as animals learned the task. For in vitro experiments, corticostriatal slice preparations were made from animals on each day of training. Results In naïve animals from both groups there was limited to no phase locking to either auditory stimulus in vivo , and long term depression resulted from theta burst stimulation in vitro . Furthermore, intrinsic and synaptic properties in normal hearing animals were unaffected; however, the hearing loss group continued to show lowered synaptic inhibition, synaptic hyperexcitation, and suppressed intrinsic excitability in the hearing loss group. Starting around day 3–4 in both groups, the emergence of striatal medium spiny neuron phase locking to the auditory conditioning stimuli was observed in vivo . This occurred contemporaneous to an increased probability of theta burst induced LTP during MSN whole cell recording in vitro , and acquisition of the task as the correct rejection response significantly increased in the behaving animals. During the acquisition phase MSNs in the normal hearing group showed a significant decrease in synaptic inhibition and increase in synaptic excitation with no change to intrinsic excitability, while the MSNs in the hearing loss group showed a significant increase in synaptic inhibition, reduction of synaptic hyper excitability, and compensatory changes to intrinsic excitability that supported normal action potential generation. In both groups, synaptic properties were resolved to similar level of E/I balance that could be part of a conserved learning state. Discussion These changes to the intrinsic and synaptic properties likely support LTP induction in vivo and the strengthening of synapses between auditory inputs and MSNs that facilitate neuronal phase locking. These findings have significant implications for our understanding of striatal resilience to sensory impairments in early life, in addition to establishing a granular understanding of the striatal circuit changes that support reward driven stimulus–response learning.

Adeno-associated virus-based gene therapy offers a promising treatment paradigm for inner ear diseases; however, the genetic heterogeneity of hereditary deafness requires gene-specific strategies and optimization of current approaches to identify the range of treatable conditions and improve therapeutic outcomes. To consider the therapeutic potential for a hearing loss gene not previously explored, we investigated the gene encoding the chloride intracellular channel protein CLIC5, mutations in which lead to DFNB103 in humans and deafness and circling behavior in a Clic5 -deficient mouse model. In this study, we utilized two constructs to deliver the wild-type Clic5 coding sequence into Clic5 -deficient mice: single-stranded and self-complementary adeno-associated virus, the latter known for rapid onset of transgene expression. We report a robust restoration of CLIC5 expression using either construct, including prevention of morphological degeneration and preserving auditory and vestibular function. Interestingly, the self-complementary construct achieved comparable functional recovery to single-stranded construct but at a lower titer. These findings highlight the potential of self-complementary adeno-associated virus to reduce dose requirements, minimize toxicity and broaden clinical utility for inner ear therapies.

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.

The homozygous Cntnap2 knockout (KO) rat is a well-established genetic model for neurodevelopmental disorders, exhibiting core features of autism spectrum disorder (ASD), including impaired sensory processing and sensorimotor gating. Recent findings indicate that the severity of ASD-like phenotypes in Cntnap2 KO offspring is influenced by the parental genotype, with more pronounced impairments observed in KO rats bred from homozygous pairs compared to heterozygous pairs ( Cntnap2 HET). However, it is unclear to what extent this is due to in utero versus postnatal effects. We, therefore, investigated how early postnatal environmental factors, shaped by differences in parental and littermate genotypes, influence auditory processing and sensorimotor gating in Cntnap2 KO rats. To examine this, we cross-fostered Cntnap2 KO pups bred from Cntnap2 KO rats to be reared with litters of Cntnap2 HET dams. Cross-fostering Cntnap2 KO rats reversed or partially reversed delayed hearing sensitivity maturation, heightened acoustic startle responses, and deficits in prepulse inhibition of the acoustic startle response. However, cross-fostering also exacerbated deficits in the neural responsiveness and conductivity in the auditory brainstem, as well as in gap-induced prepulse inhibition of the acoustic startle response. These results emphasize the importance of considering the postnatal environment and breeding strategies in preclinical genetic models of neuropsychiatric disorders. More importantly, they also demonstrate that ASD-like traits, including alterations in brainstem sensory processing, are not strictly determined by genetic factors, but remain malleable by environmental factors during early postnatal development.

Cisplatin-induced hearing loss is a common and irreversible side effect affecting a significant proportion of cancer patients. While various strategies to mitigate this toxicity have been explored, there remains a critical need for effective treatments. A major challenge in developing new therapies is the lack of reliable animal models that accurately replicate the clinical use of cisplatin in humans, which typically involves multiple cycles of low-dose administration. Traditional models using high doses of cisplatin have resulted in high mortality and variable hearing loss, complicating the assessment of potential treatments. To address this, a multi-cycle model using lower cisplatin doses in mice was developed, providing hearing loss without mortality. However, variability in outcomes across different research groups persisted. In the present study, we optimize the multi-cycle model of cisplatin-induced ototoxicity by using clinical-grade cisplatin rather than laboratory-grade formulations. The use of clinical cisplatin ensures greater consistency, reliability, and relevance to human treatment protocols, as it adheres to the rigorous quality standards required for patient use. This new administration protocol will minimize variability across research laboratories and more accurately mimic the dosing regimens typically administered to cancer patients. Additionally, we have enhanced a zebrafish model for high-throughput screening of potential therapeutics, further improving the consistency of results. These improvements to the animal models are critical for accelerating the discovery and testing of therapies to prevent cisplatin-induced hearing loss, supporting the development of effective treatments for cancer patients undergoing cisplatin chemotherapy.

The striatum is the primary input nucleus of the basal ganglia, integrating a dense plexus of inputs from the cerebral cortex and thalamus to regulate action selection and learning. Neuroanatomical mapping of the striatum and its subcompartments has been carried out extensively in rats and mice, nonhuman primates, and cats allowing comparative neuroanatomy studies to derive heuristics about striatal composition and function. Here, we systematically map corticostriatal topography from motor, somatosensory, auditory, and visual cortices as well as thalamostriatal parafascicular (PfN) inputs in the Mongolian gerbil. We also map a pathway reported in mice from medial vestibular nucleus to the PfN that could convey vestibular information to the striatum. Our findings align with those of similar studies in other rodents, indicating homologous neuroanatomical connectivity patterns within the corticostriatal projectome across Rodentia. We observed corticostriatal peaks of dense labeling for each input with a diffuse projection throughout striatal subregions from each cortical region, suggesting a global integration of all cortical information by the striatum. Thalamostriatal projections from PfN covered most of the striatum with a peak of PfN-specific compartmentalized labeling similar to other sensory and motor systems. We also confirm the connection from the medial vestibular nucleus to PfN thalamus, indicating that vestibular information may be widely integrated throughout the striatum. The findings build upon our body of knowledge on striatal connectivity across mammalian species and provide a foundation for striatal research focusing on vestibulothalamostriatal circuits in Rodentia.

Loud noise exposure is one of the leading causes of permanent hearing loss. Individuals with noise-induced hearing loss (NIHL) suffer from speech comprehension deficits and experience impairments to cognitive functions such as attention and decision-making. Here, we investigate the specific underlying cognitive processes during auditory perceptual decision-making that are impacted by NIHL. Gerbils were trained to perform an auditory decision-making task that involves discriminating between slow and fast presentation rates of amplitude-modulated (AM) noise. Decision-making task performance was assessed across pre- versus post-NIHL sessions within the same gerbils. A single exposure session (2 h) to loud broadband noise (120 dB SPL) produced permanent NIHL with elevated threshold shifts in auditory brainstem responses (ABRs). Following NIHL, decision-making task performance was tested at sensation levels comparable to those prior to noise exposure in all animals. Our findings demonstrate NIHL diminished perceptual acuity, reduced attentional focus, altered choice bias, and slowed down evidence accumulation speed. Finally, video-tracking analysis of motor behavior during task performance demonstrates that NIHL can impact sensory-guided decision-based motor execution. Together, these results suggest that NIHL impairs the sensory, cognitive, and motor factors that support auditory decision-making.