Given the observed interaction and reports of oxytocin, μ-opioid receptor, or κ-opioid receptor expression in brain regions important to emotion regulation (i.e., the central amygdala), we hypothesized that oxytocin ( oxtr ), μ-opioid ( oprm1 ), and κ-opioid ( oprk1 ) receptor mRNA were colocalized to the same cells in the central amygdala. RNAscope in situ hybridization performed on fresh-frozen coronal brain sections was used to label cells containing oxtr , oprm1 , and/or oprk1 . The coronal sections were imaged using a 40× objective (widefield fluorescence) on a Leica Thunder fluorescent microscope, and the images were processed using open-source ImageJ/Fiji software and analyzed using the Imaris software. The central amygdala was identified using Paxinos and Watson's The Mouse Brain in Stereotaxic Coordinates ( [Paxinos and Franklin, 2019][1]). Eight distinct cell populations were enumerated (i.e., oxtr -only, oprm1 -only, oprk1 -only, oxtr  +  oprm1 -only, oxtr  +  oprk1 -only, oprm1  +  oprk1 -only,...

Depression and anxiety are often characterized by altered reward-seeking and avoidance, respectively. Yet less is known about the relationship between depressive symptoms and specific avoidance behaviors. To address this gap, we conducted two studies. In Study 1, undergraduates and online workers completed an uninstructed go/no-go avoidance task ( N Total = 465) as a reverse translation of a rodent paradigm. Participants exhibited a wide range of symptom scores on the Beck Depression Inventory-II (BDI-II), ranging from low to severe. In Study 1, cues were used to signal the response type (go/active vs. no-go/inhibitory) required to avoid an aversive sound. Higher depressive scores were associated with poorer acquisition of active avoidance in undergraduates. Overall participants showed lower accuracy for active than inhibitory avoidance. To examine whether the better No-go trial performance reflected a prepotent response to avoid aversive outcomes, in Study 2, undergraduates ( N Total = 330) completed a ve...

The causal relationship between gut microbiota (GM) and white matter injury and communication remains unclear. We aimed to scrutinize the plausible causal impact of GM on white matter hyperintensities (WMHs), white matter microstructure, white matter connectivity, and multiple neurological diseases via Mendelian randomization study. We identified four WMH-related bacterial taxa, including class Melainabacteria , order Gastranaerophilales , family Alcaligenaceae , and genus Ruminiclostridium 6 . In addition, three bacterial taxa were discovered that have consistent effect on multiple aspects of white matter microstructure. Furthermore, we found 12 strong associations between genetic liability in GM and white matter connectivity. Among these bacterial taxa, the family Clostridiaceae 1 demonstrated a protective effect against ischemic stroke (IS). The genus Barnesiella showed protective effect on IS and small vessel stroke while posed a risk effect on neuromyelitis optica spectrum disorder (NMOSD), as well as...

The corticospinal tract (CST) facilitates skilled, precise movements, which necessitates that subcerebral projection neurons (SCPNs) establish segmentally specific connectivity with brainstem and spinal circuits. Developmental molecular delineation enables prospective identification of corticospinal neurons (CSNs) projecting to thoraco-lumbar spinal segments; however, it remains unclear whether other SCPN subpopulations in developing sensorimotor cortex can be prospectively identified in this manner. Such molecular tools could enable investigations of SCPN circuitry with precision and specificity. During development, Kelch-like 14 ( Klhl14 ) is specifically expressed by a specific SCPN subpopulation, CSNBC-lat, that reside in lateral sensorimotor cortex with axonal projections exclusively to bulbar-cervical targets. In this study, we generated Klhl14-T2A-Cre knock-in mice to investigate SCPN that are Klhl14+ during development into maturity. Using conditional anterograde and retrograde labeling in mice of ...

Angelman syndrome (AS) is a rare neurodevelopmental disorder caused by loss of expression of the maternal UBE3A allele and is characterized by a constellation of impactful neurologic symptoms. While previous work has uncovered outsized contributions of GABAergic neuron-selective Ube3a deletion to seizure susceptibility and electroencephalography (EEG) phenotypes in a mouse model of AS, the neuronal populations governing a broader range of behaviors have not been studied. Here, we used male and female mice to test the consequences of Ube3a deletion from GABAergic or glutamatergic neurons across a well-characterized battery of AS-relevant behaviors. Surprisingly, we observed deficits in numerous motor and innate behaviors in mice with glutamatergic Ube3a deletion and relatively few consequences of GABAergic Ube3a deletion. Furthermore, genetic Ube3a reinstatement in glutamatergic neurons rescued multiple motor and innate behaviors. When tested for sleep–wake behaviors, the selective loss of Ube3a from glutam...

Rhythmic network states have been theorized to facilitate communication between brain regions, but how these oscillations influence communication subspaces, i.e., the low-dimensional neural activity patterns that mediate interregional communication, and in turn how subspaces impact behavior remain unclear. Using a spatial memory task in rats (male Long–Evans rats), we simultaneously recorded ensembles from hippocampal CA1 and the prefrontal cortex (PFC) to address this question. We found that task behaviors best aligned with low-dimensional, shared subspaces between these regions rather than local activity in either region. Critically, both network oscillations and speed modulated the structure and performance of this communication subspace. To understand the communication space, we visualized shared CA1–PFC communication geometry using manifold techniques and found ring-like structures. We hypothesize that these shared activity manifolds are utilized to mediate the task behavior. These findings suggest th...

When compared with nature sounds, exposure to mechanical sounds evokes higher levels of perceptual and physiological arousal, prompting the recruitment of attentional and physiological resources to elicit adaptive responses. However, it is unclear whether these attributes are solely related to the sound intensity of mechanical sounds, since in most real-world scenarios, mechanical sounds are present at high intensities or if other acoustic or semantic factors are also at play. We measured the skin conductance response (SCR), reflecting sympathetic nervous system activity as well as the pleasantness and eventfulness of the soundscape across two passive and active listening tasks in healthy subjects ( N  = 25; 14 females, 11 males). The auditory stimuli were divided into two categories, nature and mechanical sounds, and were manipulated to vary in three perceived loudness levels. As expected, we found that the sound category influenced perceived soundscape pleasantness and eventfulness. SCR was analyzed by t...

The corticospinal tract (CST) is essential for forelimb-specific fine motor skills. In rodents, it undergoes extensive structural remodeling across development, injury, and disease states, with major implications for motor function. A vast body of literature, spanning numerous injury models, frequently assesses these projections. Despite this, a cohesive imaging modality for rapid, quantitative assessment of the bilateral cervical spinal cord projectome is lacking. To address this, we developed SpinalTRAQ (Spinal cord Tomographic Registration and Automated Quantification), a novel mouse cervical spinal cord volumetric reference atlas and machine learning-based analytical pipeline. Using serial two-photon tomography, SpinalTRAQ enables unbiased, region-specific quantification of fluorescently labeled CST presynaptic terminals. In healthy male mice, the CST exhibits a distinct bilateral synaptic projectome, with the densest innervation in laminae 5 and 7 on the contralateral side and lamina 7 on the ipsilate...

Pathological levels of beta amyloid (Aβ) lead to disruption and elimination of synapses in brain as the result of direct neurotoxicity as well as neuroinflammation. The synaptic impact of beta amyloid includes altered morphology and reduced number of dendritic spines at excitatory synapses, evident in the brains of individuals with Alzheimer’s disease. Here, we assessed the ability of an identified neuroprotective peptide, YEVHHQ, derived from the N-terminal domain of Aβ, known as the AβCore, to protect against Aβ-induced alterations in dendritic spines. Our approach involved both 2D and 3D imaging of spine morphology in hippocampal neuron cultures from mice of either sex, with the 3D imaging focusing on the postsynaptic density (PSD), as its morphology is tightly correlated with synaptic strength, and presynaptic terminal morphology and density to assess the impact on both sides of the synapse. We present evidence for uniform prevention by the AβCore of Aβ-induced reductions in spine cross-sectional size ...

Aversion modulation is a key component of hedonic processing, and its dysfunction is evident in psychiatric illnesses. The infralimbic cortex (IL) to nucleus accumbens shell (NAcSh) pathway is essential in hedonic processing in rodents but operates differentially across sex, with beta (20 Hz) oscillatory activity involved in learned aversion in male but not female rats. In this study, we used taste reactivity (TR) and electrophysiology to examine the role of high gamma (80 Hz) activity in affect modulation, specifically innate (quinine) and learned (conditioned taste aversion, CTA) aversion, in male and female Sprague Dawley rats. Local field potential (LFP) recordings in males showed no changes in IL or NAcSh activity, or in IL→NAcSh functional connectivity, in the high gamma frequency band during innate or learned aversion. In contrast, in females, quinine elicited an increase in IL and NAcSh 80 Hz LFP activity and IL→NAcSh functional connectivity. Interestingly, LFP directionality analyses in females in...