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,...

Understanding the roles of astrocytic calcium signaling in multiple brain regulatory mechanisms including metabolism, blood flow, neuromodulation, and neuroinflammation has remained one of the enduring challenges in glial biology. To delineate astrocytic contribution from concurrent neuronal activity, it is vital to establish robust control and manipulate astrocytes using a technique like optogenetics due to its high cellular specificity and temporal resolution. The lack of an experimental paradigm to induce controlled calcium signaling in astrocytes has hindered progress in the field. To address this, in this study, we systematically characterize and identify light stimulation paradigms for inducing regulated, on-demand increases in astrocytic calcium in acute brain slice cortical astrocytes from MlC1-ChR2(C128S)-EYFP mice (of either sex). We identified paradigms 20, 40 and 60% (of T  = 100 s) to elicit robust calcium responses upon periodic stimulations, while the 95% paradigm exhibited a response only d...

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...

Current models of motor control emphasize the critical role of sensory feedback, as demonstrated by movement coordination deficits following sensory impairment. When both vision and touch are available for object-oriented manual behaviors, they serve distinct roles; vision guides the execution of planned movements, while touch provides more direct feedback on hand–object interactions. The impact of losing somatosensory feedback on eye–hand coordination during dexterous object manipulation tasks has not been thoroughly studied. Conceivably, vision is recruited to compensate for the feedback lost when touch is abolished based on the dexterity demands of the behavior. To investigate this, we tested healthy participants of either sex on a manual dexterity task requiring the movement of small metal pegs, both before and after the administration of digital anesthesia, which selectively abolished cutaneous sensations in the fingertips while preserving motor function. We recorded participants' gaze and hand positi...

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...

Cancer patients experience circadian rhythm disruptions during and after chemotherapy that can contribute to debilitating side effects. It is unknown how chemotherapy mediates circadian disruptions and specifically the extent to which these disruptions occur at the level of the principal clock, the suprachiasmatic nuclei (SCN) of the hypothalamus. In the present study, we assessed how the commonly used chemotherapeutic, paclitaxel, impacts the SCN molecular clock and SCN-dependent behavioral adaptations to circadian challenges in female mice. Following a repeated chemotherapy regimen, we measured rhythmic SCN expression of molecular clock and circadian-associated transcripts. Paclitaxel chemotherapy disrupted the SCN molecular clock through abolished rhythmicity ( Bmal1 , Nr1d2 ) and damped rhythmic transcription ( Ciart , Dbp , Nr1d1 , Per2 ) of key molecular clock genes. We further determined chemotherapy-induced changes to SCN function by measuring circadian wheel running adaptations to a jet lag phase-...

The sense of body ownership, a core aspect of self-recognition, has been studied using illusions such as the full-body illusion. Although the premotor cortex is considered central to body ownership in first-person full–body illusions, the occipitotemporal cortex—including the temporoparietal junction (TPJ) and the extrastriate body area (EBA)—also plays a critical role in third-person full–body illusions. However, their distinct contributions to the full-body illusion remain unclear, partly due to the challenges of applying neuroimaging in such experiments. This study employed functional near-infrared spectroscopy to investigate brain activity during a third-person full–body illusion in virtual reality. Eighteen healthy human adult males participated in the study. The experiment consisted of two sessions. In Session 1, participants observed an avatar's back receiving either synchronous or asynchronous visual–tactile stimulation. In Session 2, visual stimuli alone were presented to participants after they e...