The cerebellum is well established in subsecond motor timing, but its role in suprasecond interval timing remains unclear. Here, we investigated how cerebellar output influences time estimation over longer timescales. Male rats performed a nose-poke interval timing task in which reward availability could be predicted either from a fixed 2.5 s auditory cue (cued trials) or had to be estimated internally during uncued 3.5 s trials that demanded self-timing. Chemogenetic inhibition of the lateral cerebellar nucleus (LCN) produced bidirectional effects: delayed action initiation in predictable trials and premature (∼100–160 ms) responses when self-timing was required. Despite a slowing of movement, overall task success rates remained unchanged. Because motor slowing is likely to lead to later, not earlier, action initiation, these results implicate the LCN in computing internal time estimates. These findings demonstrate that the cerebellum integrates motor and cognitive processes for suprasecond timing, with d...

There is a critical need for robust and reliable preclinical models for posttraumatic stress disorder (PTSD) to better understand pathophysiological mechanisms and support the development of novel treatments. The single prolonged stress (SPS) model has been previously utilized to investigate various acute behavioral effects and stress hormone changes in rodents. This study paired anxiety-like and social behavioral evaluations with corticosterone assessment as a complementary physiological biomarker to determine the presence of robust and intervenable phenotypes following SPS. Sprague Dawley rats ( N  = 36, 30 male and 6 female) received SPS model induction (e.g., restraint with odorant, forced-swim, diethyl ether exposure, and isolation) or control handling. Serum corticosterone and behavioral assessments, including the open field test (OFT) and a social motivation test (SMT), were investigated at 1 and 2 weeks following SPS induction. This SPS model did not induce anxiety-like or locomotive differences as...

Social cognition, central to emotional and cognitive well-being, is particularly vulnerable to aging, where impairments can lead to isolation and functional decline. Despite compelling evidence that altered social behavior is associated with cognitive decline and dementia risk, experimental strategies for testing causative links remain scarce. To address this gap, we aimed to establish a rat model for research on social neurocognitive aging. We conducted a large-scale behavioral study in 169 male young (6 months) and aged (24–25 months) Long–Evans rats. In order to explore potential relationships among aging outcomes, we first documented individual differences in a widely validated water maze test of hippocampal learning and memory. Sociability and social novelty were then evaluated in the same subjects using the three-chamber social interaction test. Aging induced a selective shift in social novelty preference, marked by a striking familiarity bias in a substantial subpopulation of old rats, while sociabi...

Spastin is a conserved microtubule-severing enzyme mutated in hereditary spastic paraplegia. The role that spastin plays in the cell biology of axon regeneration and degeneration has recently been investigated in Drosophila . We show that the C. elegans spastin ortholog, spas-1 , is expressed in GABA motor neurons, in addition to the known expression in touch receptor neurons (TRNs) and that it is required for axon regeneration in the GABA motor neurons after in vivo laser axotomy. We identified no neuronal developmental defects in the GABA motor neurons and only minor branching variations in the TRNs. However, we show that spas-1 is required for the long-term maintenance of TRN axons in C. elegans , as older spas-1 null C. elegans show a significant increase in specific axonal morphological defects compared with the wild type as identified by confocal microscopy in aged animals. Together, our results suggest that spastin is required for regrowth and maintenance of axons in C. elegans , consistent with pre...

The progressive ratio (PR) schedule is a popular and well-established tool used to study decision-making and effort across species. In this task, subjects perform an instrumental response to receive a reinforcement, but the ratio requirement increases throughout the behavioral session. A subject's breakpoint, or the point at which the subject is no longer willing to exert the effort required to receive reinforcement, is the main behavioral readout analyzed in the PR schedule. The PR schedule has been used to investigate motivation for various reinforcers (e.g., drugs of abuse) and has been adapted to incorporate aspects of effort-related decision-making (e.g., choice between high- and low-value outcomes). However, there are notable limitations to the utility of the PR as a test of decision-making, including the confounding effects of effort and delay in that higher ratios take longer to complete, the limited behavioral response options (e.g., lever pressing), and breakpoint being a low-dimensional measurem...

Dementia-causing diseases, including Alzheimer's disease (AD), are one of the greatest health concerns facing the aging world population. A key feature of AD is excessive accumulation of amyloid-beta, leading to synapse and cell loss in brain structures, such as the hippocampus. This neurodegeneration is preceded by impaired neuron function, notably reduced synaptic inhibition. Metabotropic GABAB receptors (GABABRs) may be modulated by amyloid precursor protein (APP) and are reported to be progressively lost from neuronal membranes of hippocampal pyramidal neurons. However, it remains unknown whether functional GABABR-mediated signaling changes over aging and whether or not pharmacological intervention can prevent receptor loss. In this study, we combine electrophysiological and biochemical analysis of hippocampal neurons in the Amyloid Precursor Protein/Presenilin-1 (APP/PS1) mouse model of AD from acute brain slices and organotypic slice cultures prepared from male and female mice to determine if functio...

Galanin-expressing neurons in the ventrolateral preoptic area (VLPOgalanin) are active during sleep and play an important role in regulating non-rapid eye movement (NREM) sleep. It is generally believed that VLPOgalanin neurons promote sleep via inhibitory actions in arousal-promoting regions of the brain. Histaminergic neurons are a population of wake-active neurons that receive strong projections from the sleep-active VLPOgalanin neurons. However, the ability of galanin to influence the activity of histaminergic neurons has received limited attention. Here, using whole-cell patch-clamp electrophysiological recordings from genetically identified histaminergic neurons in male mice, we explore the mechanisms by which galanin influences histaminergic neuron electrical excitability. Our results reveal that galanin is a powerful inhibitor of histaminergic neuron activity and demonstrate that the inhibitory effects of galanin are mediated by galanin receptor 1 (GALR1) and the subsequent opening of G-protein-cou...

Neurite outgrowth is essential for neural circuit formation and is tightly regulated by secreted factors and their receptors. The secreted extracellular domain of the amyloid precursor protein (sAPPα) has been shown to modulate neurite outgrowth. Recently, the gamma amino butyric acid receptor type-B subunit 1a (GABABR1a) was identified as an sAPPα binding partner that mediates its effects on synaptic transmission. Here, we investigated whether this interaction also regulates neurite outgrowth. In mouse primary hippocampal neurons of either sex, the GABABR agonist baclofen reduced axon length; whereas its antagonist CGP54626 increased axon length in primary hippocampal neurons. Moreover, GABABR1a knock-out increased axon length and abolished the effect of baclofen. Application of sAPPα reduced axon length, an effect that required the presence of both GABABR1a and the extension domain of sAPPα, which mediates its binding to GABABR1a. Similarly, the APP 17mer peptide, which is sufficient to bind GABABR1a and...

Auditory-evoked EEG signals contain rich temporal and cognitive features that reflect both the identity of individuals and their neural response to external stimuli. Traditional unimodal approaches often fail to fully leverage this multidimensional information fully, limiting their effectiveness in real-world biometric and neurocognitive applications. This study aims to develop a unified deep learning model capable of jointly performing biometric identification, auditory stimulus language classification, and device modality recognition, thereby exploiting both physiological and cognitive dimensions of auditory-evoked EEG. We introduce TriNet-MTL (Triple-Task Neural Transformer for Multitask Learning), a multi-branch deep learning framework composed of a shared temporal encoder and a transformer-based sequence modeling unit, trained and validated on auditory-evoked EEG data from 20 human participants (16 males and 4 females). The architecture is designed to simultaneously learn task-specific features via th...

Blocking is a key statistical method introduced almost a century ago by Ronald Fisher. Blocking controls the effect of “nuisance” variables that are not of direct interest but introduce unwanted variation into the experimental response. Block factors, such as cage, litter, or time, are used to group experimental units into homogeneous subsets. There are two types of block designs: complete and incomplete. In complete block designs every treatment appears in every block. Examples include the Randomized Complete Block Design (RCBD) with a single block factor, and variants such as Latin square and Graeco-Latin square designs with multiple block factors. RCBDs are simple, flexible, and the most widely used. Replicated and nested Latin square designs allow more rigorous control of complex nuisance structures with minimal sample size. Incomplete block designs are extremely useful when practical constraints (e.g., caging density or varying litter sizes) restrict complete treatment replication across all blocks. B...