The tail suspension test (TST) is a well-known rodent behavioral test that assesses stress and depressive-like behavior. While several automatic tail suspension test scoring programs have emerged, many researchers still prefer a manual scoring method for accuracy and reliability. However, manual scoring can introduce significant errors. Thus, in this work, we present a novel graphical user interface that assists in the manual scoring process to minimize possibility for errors. The GUI, which we refer to as “TST Score Helper,” minimizes errors through consolidation of the TST scoring procedure into a single cohesive program. Further, a rescore mode enhances rigor by enabling comparison of two different scorers’ mobility status timelines and rereview of periods of disagreement. In a cohort of 64 male and 45 female mice subject to closed head injury or sham injury, we demonstrate the challenges with manual scoring and we characterize performance of the TST Score Helper program. The results show how this progr...

Proteomic studies have generated robust assessments of protein abundance changes in Alzheimer's disease (AD); however, identifying how the protein abundance changes affect specific biological processes remains a challenge. To address these hurdles, we used a multi-network computational analysis approach that integrated dendritic spine morphometry data with mass spectrometry-based proteomics from the same individuals. The samples exhibited a range of AD neuropathology and were categorized into three groups: controls, asymptomatic AD, and AD cases. Multiplex tandem mass tag mass spectrometry proteomic data ( N  = 8,212 proteins) was generated on Brodmann area 46 (BA46) dorsolateral prefrontal cortex (DLPFC) human samples ( N  = 41, 23 males and 18 females), from which dendritic spine morphometry analysis existed. To integrate the multi-scale data types, two computational network analysis methods were performed, including weighted coexpression network analysis (WGCNA) and SpeakEasy2 (SE2). Both WGCNA and SE2 ...

Selective attention is often divided into voluntary (goal-directed) and involuntary (stimulus-driven) forms, a distinction extensively studied for attention to external sensory input. In contrast, internal selective attention—directed toward representations held in working memory (WM)—has been considered primarily for voluntary influences. Recent behavioral evidence suggests that task-irrelevant external stimuli can also influence internal selection of feature-matching WM representations involuntarily, yet the neural mechanisms underlying these effects remain unclear. Here, we tested whether an uninformative exogenous spatial retro-cue presented during a WM delay can act as a selective “ping” and reactivate spatially matching WM content at the level of its representational category. Male and female human participants memorized complex contents presented at distinct locations, followed by unpredictive and task-irrelevant spatial retro-cues that conveyed no category information. Using temporally resolved mul...

Fragile X syndrome is a leading cause of intellectual disability and autism spectrum disorder, for which therapies are limited. A mouse model of fragile X syndrome, the Fmr1 knock-out (KO) mouse, has been particularly valuable for interrogating the molecular, cellular, and circuit mechanisms that underlie the neurological deficits seen in this syndrome. Key deficits in fragile X syndrome include impairments in social behaviors, cognition, and motor learning. Given the difficulties in extrapolating complex human behaviors to mouse models, motor behaviors are a particularly tractable form of learning to study in the mouse. We investigated a form of forelimb reach learning in both male and female Fmr1 KO mice, quantifying different parameters of the task using both manual analysis and DeepLabCut-based tracking of reach trajectories. While Fmr1 KO mice show impaired learning overall, our results showed that the presence or absence of a cue that signals reward alleviated some of the deficits. In addition to a s...

Epigenetic and transcriptional mechanisms are key contributors to alcohol use disorder (AUD). However, a better understanding of the specific genes, transcripts, and chromatin marks affected is necessary to inform novel pharmacotherapies. Here, we systematically investigate the genome-wide epigenetic and transcriptomic effects of ethanol across key brain regions relevant to AUD and assess how these outcomes differ between acute and chronic exposure in male C57BL/6J mice. We show that alcohol-derived acetate contributes to histone acetylation in the brain in response to acute or chronic exposure, with a broader and more robust effect following repeated exposure. Further, we find that chromatin and transcriptomic changes elicited by acute or chronic ethanol exposure are predominantly specific to brain region and observe more robust dysregulation of gene and transcript expression following acute exposure. We show that ethanol-induced transcriptional changes are paradigm dependent in some brain regions, most s...

Echolocation enables blind individuals to perceive and navigate their environment by emitting clicks and interpreting their returning echoes. While expert blind echolocators demonstrate remarkable spatial accuracy, the behavioral and neural mechanisms by which spatial echoacoustic cues are combined across repeated samples remain less explored. Here, we investigated the temporal dynamics of spatial information processing in human click-based echolocation using electroencephalography (EEG). Blind expert echolocators ( n  = 4, all males) and novice sighted participants ( n  = 21, 12 males) localized virtual spatialized echoes derived from realistic synthesized mouth clicks, presented in trains of 2–11 clicks. Behavioral results showed that blind expert echolocators significantly outperformed sighted controls in spatial localization. For these experts, localization thresholds decreased as the number of clicks increased, a pattern consistent with cumulative integration of spatial information across repeated sam...

We lack a mechanistic understanding of how cortical contributions to balance control change in aging and Parkinson's disease (PD). Balance is governed by brainstem circuits, with higher-order centers like the cortex or basal ganglia becoming engaged as challenge increases or balance health declines. We previously showed that parallel sensorimotor feedback loops engaging brainstem and cortical circuitry contribute to muscle activity for balance control in young adults (YAs). Here, we analyze data from male and female older adults (OAs) with and without PD, decomposing perturbation-evoked tibialis anterior and medial gastrocnemius muscle activity into hierarchical components based on latencies of feedback control loops. We found that balance-correcting muscle activity followed a stereotypical waveform of long-latency responses (LLRs): LLR1 began ∼120 ms and LLR2 occurred ∼210 ms, respectively, consistent with subcortical and cortical feedback latencies. Both LLRs increased with balance challenge and could be...

Ras-related C3 botulinum toxin substrate 1 (Rac1) is a small GTPase that regulates actin cytoskeleton dynamics and synaptic plasticity. Rac1 has been implicated in active forgetting, but whether it also constrains the consolidation of new memories remains unclear. Here we show that systemic administration of the Rac1 inhibitor 1A-116 after training in the novel object recognition task markedly extends memory persistence in rats. A single post-training injection of 1A-116 enhanced recognition memory for at least 28 d without altering locomotor- or anxiety-related behaviors. When given after a brief, subthreshold training session that normally supports only short-term memory, 1A-116 enabled long-term retention that required hippocampal protein synthesis. This promnesic effect was time-dependent, independent of sex, and consistent with Rac1 acting as a negative regulator of memory consolidation rather than merely promoting forgetting. These findings indicate that Rac1 activity after learning limits the consol...

Bipolar cells relay visual signals from photoreceptors to ganglion cells. In the mouse retina, 15 bipolar cell subtypes have been identified and are classified as ON or OFF bipolar cells based on their responses to light or as rod or cone bipolar cells based on their photoreceptor connectivity. Despite this diversity, the distinct structural and functional roles of bipolar cell subtypes in visual information processing remain poorly understood, largely due to lack of tools and models for their characterization. In this study, we generated inducible Cre mouse lines driven by the promoters of Vsx1 , Lhx3 , and Lhx4 and crossed them with ChR2EYFP reporter mice to trace lineage and characterize bipolar cell subtypes in postnatal and adult mouse retinas. Following tamoxifen induction in adult male and female mice, ChR2EYFP expression was detected in type 2, 6, and 7 bipolar cells in the Vsx1 CreERT2 line; type 1b, 2, and 6 bipolar cells in the Lhx3 CreERT2 line; and type 2, 3, 4, and 5 bipolar cells in the Lhx4...

Environmental enrichment (EE) reduces vulnerability to multiple drugs of abuse, yet its impact on fentanyl use and relapse-like behavior remains unclear. Here, we tested whether long-term, nonsocial, object-based EE alters fentanyl self-administration, extinction, and stress-induced reinstatement in male and female rats. Rats were individually housed in either standard nonenriched (NE) conditions or in EE cages containing a rotating set of novel objects beginning at least 3 d prior to self-administration. EE did not impact acquisition of fentanyl self-administration but reduced fentanyl intake during maintenance of self-administration and reduced the persistence of drug-seeking in extinction. Following extinction, yohimbine robustly reinstated drug-seeking behavior in NE rats but reinstatement in EE rats was markedly attenuated, indicating reduced sensitivity to stress-induced relapse triggers. Circulating corticosterone levels were lower in EE rats across the experiment and were positively correlated with...