Alcohol use disorder (AUD) imposes a significant global health burden, yet effective treatments remain limited. There are no well-characterized, AUD-relevant, rodent biological sample repositories to support research in this area. To address this gap, we established the Alcohol Biobank, a comprehensive resource containing thousands of samples from over 700 (half males, half females) genetically diverse heterogeneous stock (HS) rats. Modeled after two successful cocaine and oxycodone biobanks, this repository uses the chronic intermittent ethanol vapor exposure (CIE) model, paired with oral self-administration, to characterize AUD-like behaviors, including ethanol consumption, preference, motivation, and withdrawal symptoms such as allodynia and anxiety-like behavior. Longitudinal samples (blood, urine, and feces) are collected before, during, and after ethanol exposure, while tissue samples (brain, heart, kidneys, liver, cecum, reproductive organs, adrenal glands, blood) are obtained at intoxication, acute...

The environment experienced by children, such as exposure to chronic early life adversity (ELA), increases lifespan brain disorder risk. The mechanisms that link ELA exposure to functional brain disruptions are not well understood. A limited-bedding and nesting paradigm, in which ELA is induced in mouse pups over the first postnatal week through disruption of maternal care, is characterized by limited resources, environment unpredictability, and disruption of reward and cognitive behaviors. Studies using this model demonstrated sex-selective alterations in hippocampal mitochondrial-associated proteins in response to ELA compared with care as usual (CAU). Further, oxidative phosphorylation (OXPHOS) capacity and complex I activity are increased in ELA juveniles, yet decreased in adults, with the impact of ELA moderated by sex in adults. Given that altered mitochondrial function is a key mediator in metabolic adaptations, the goal of the present study was to evaluate the possibility of reversing mitochondrial...

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,...

The plasma membrane acts as a capacitor that plays a critical role in neuronal excitability and signal propagation. Neuronal capacitance is proportional to the area of the cell membrane; thus it is often used as a measure of the cell size that is assumed to be relatively stable. Recent work proposes that the capacitance of dentate granule cells (dGCs) and cortical pyramidal cells changes across the light/dark (LD) cycle in a manner that alters synaptic integration. We addressed this potential change in capacitance using a large dataset of dGC recordings from adult male and female mice across the light cycle. Our data show that daily changes in the membrane time constant result from fluctuation in membrane resistance rather than capacitance. We also confirm the ability to resolve changes in neuronal capacitance induced by altering dGC membrane area via acute axotomy or genetically induced overgrowth using either voltage-clamp or current-clamp approaches. Our results demonstrate that the capacitance of dGCs ...

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...

Chemotherapy can cause debilitating behavioral side effects (e.g., fatigue, depression, cognitive decline); however, having an intimate partner can buffer these effects. The California mouse ( Peromyscus californicus ) is a rare monogamous mouse species that offers a novel opportunity to model human intimate partnership to identify the neurobiological mechanisms by which mate bonding reduces chemotherapy-associated behavioral side effects. As a first step toward this goal, this pilot study aimed to develop the first chemotherapy model, to our knowledge, in adult male and female California mice. Following a repeated paclitaxel chemotherapy regimen, well characterized in laboratory mice ( Mus musculus ), gross sickness physiology was first assessed after various doses. The 20 mg/kg paclitaxel dose, injected six times every other day, was the highest tolerable, clinically relevant dose and was characterized by moderate body mass loss and increased spleen mass. Thus, further investigation of the effects of thi...

Understanding how neural circuits integrate sensory and state information to support context-dependent behavior is a central challenge in neuroscience. Oviposition is a complex process during which a fruit fly integrates context and sensory information to choose an optimal location to lay her eggs. The circuit that controls oviposition is known, but how the oviposition circuit integrates multiple sensory modalities and internal states is not. Using the Hemibrain connectome, we identified the oviposition inhibitory neuron (oviIN) as a key hub in the oviposition circuit and analyzed its inputs to uncover potential parallel pathways that may be responsible for computations related to sensory integration and decision-making. We applied a network analysis to the subconnectome of inputs to the oviIN to identify clusters of interconnected neurons—many of which are uncharacterized cell types. Our findings indicate that the inputs to oviIN form multiple parallel pathways through the unstructured neuropils of the su...

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 ver...

High-level spinal cord injury (SCI) often reduces neural regulation of cardiovascular function. During the chronic phase, humoral regulation via the renin–angiotensin system (RAS) is enhanced to compensatorily maintaining blood pressure. It was recently shown that transplanting early-stage neurons into the injured cord mitigates cardiovascular disorders. However, the mechanisms underlying this recovery remain largely unknown. Here, we employed various pharmacological interventions to elucidate whether this strategic transplantation affects the imbalance of neuroendocrine regulation of hemodynamics and the role of specific serotonergic and catecholaminergic components. Female rats received a complete crush at the fourth thoracic spinal cord. Embryonic neural progenitor cells (NPCs) harvested from the raphe nuclei or the spinal cord were transplanted into the lesion. Naive rats or injury alone served as controls. After 8–9 weeks, radio-telemetric recordings demonstrated that both implants decreased tachycard...

Current research strives to investigate cognitive processes under natural conditions. Virtual reality and EEG are promising techniques combining naturalistic settings with close experimental control. However, many questions and technical challenges remain, e.g., are saccade onsets a suitable replacement of fixation onsets as key events in continuous gaze trajectories ( [Amme et al., 2024][1]), and consequently, can VR capture differences across different stimulus categories associated with varying saccade durations? To address both questions, we investigate the N170 face effect in humans (14 males, 19 females, zero diverse) using a free-viewing and free-movement immersive VR study that contained houses, various background stimuli, and, notably, static and moving pedestrians to study face perception under naturalistic conditions. Our results show that aligning trials to saccade onsets leads to more well-defined ERPs than fixation onsets, especially for the P100 component, demonstrating that saccade-onset ER...