Perinatal exposure to the organophosphorus insecticide chlorpyrifos (CPF) is associated with an increased incidence of neurodevelopmental disorders, such as autism spectrum disorder. While these behavioral detriments have been modeled in rodents, the underlying functional alterations in the developing brain are largely unknown. Previous reports using a rat model have identified alterations to both inhibitory synaptic transmission and serotonergic (5-HT) receptor binding in the cortex following developmental CPF exposure. Here, we use a rat model of gestational CPF exposure to investigate whether this altered inhibitory activity is driven by increased spontaneous firing of inhibitory interneurons and altered 5-HT receptor expression. Using cell-attached ex vivo electrophysiology in young rats of both sexes, we identified a significant increase in the number of spontaneously firing neurons in the somatosensory cortex of CPF-exposed offspring. Analysis of action potential metrics identified a subset of these ...

Fear extinction, the gradual reduction of conditioned fear in response to a previous threatening experience that no longer predicts danger, plays a crucial role in exposure-based therapies for anxiety and trauma-related disorders. Despite the efficacy of these therapies for many, a significant number of individuals encounter difficulties in extinguishing fear, resulting in treatment resistance. Understanding the mechanisms behind the variation in extinction success among individuals remains a central pursuit in neuroscience. Recent studies have identified dopamine (DA) neurons within the ventral tegmental area (VTA) to influence the extinction process. In addition to their well-established role in signaling reward prediction errors, specific populations of VTA DA neurons also respond to the unexpected omission of an aversive stimulus, producing a signal indicative of safety. In animals capable of successful extinction, this burst of activity associated with stimulus omission diminishes over time, signalin...

Mirror invariance is the cognitive tendency to perceive mirror-image objects as identical. Mirrored letters, however, are distinct orthographic units and must be identified as different despite having the same shape. Consistent with this phenomenon, a small, localized region in the ventral visual stream, the Visual Word Form Area (VWFA), exhibits repetition suppression to both identical and mirror pairs of objects but only to identical, not mirror, pairs of letters ( [Pegado et al., 2011][1]), a phenomenon named mirror invariance “breaking”. The ability of congenitally blind individuals to “break” mirror invariance for pairs of mirrored Braille letters has been demonstrated behaviorally ( [de Heering et al., 2018][2], [Korczyk et al., 2024][3]). However, its neural underpinnings have not yet been investigated. Here, in an fMRI repetition suppression paradigm, congenitally blind individuals (8 males and 10 females) recognized pairs of everyday objects and Braille letters in identical (“p” and “p”), mirror (...

Repetitive mild traumatic brain injury (rmTBI) is a major contributor to long-term neurological dysfunction, yet many preclinical models lack precise control and quantification of biomechanical forces across impacts. We developed a reproducible, closed-skull mouse model of rmTBI using a custom-built weight–drop apparatus featuring a solenoid-based rebound arrest system, integrated high-speed videography, and accelerometry to track head kinematics during impact. Adult male and female mice received either a single impact or nine daily impacts. Linear and angular acceleration data were analyzed alongside behavioral and histological outcomes. Our apparatus delivered consistent impact and velocity forces with minimal intersubject variability. Additionally, the animals experienced consistent linear and angular acceleration as measured using high-speed video capture. These impacts did not cause skull fracture or acute vascular hemorrhage, but impacted animals had increased return of righting reflex time, consiste...

The growing therapeutic promise of repeated, low-dose ketamine treatment across various psychopathologies—including depression and drug addiction—warrants clarity on its potential addictive properties and their associated mechanisms in both sexes. Accordingly, the present work examined the effects of intermittent low-dose ketamine in male and female rats on behavioral sensitization to the locomotor-activating effects of ketamine, as well as associated molecular profiles in dopamine D1- and D2-receptor-expressing medium spiny neurons (D1- and D2-MSNs) of the nucleus accumbens (NAc). Following intra-NAc infusion of a Cre-inducible RiboTag virus, locomotor activity was measured in adult Drd1a-iCre and Drd2-iCre male and female rats in either diestrus or proestrus following repeated administration of ketamine (0, 10, or 20 mg/kg, i.p.) to evaluate the development of locomotor sensitization. Female—but not male—rats developed sensitization to the locomotor-activating effects of ketamine, occurring more rapidly ...

The nigrostriatal and mesoaccumbal dopamine systems are thought to contribute to changes in behavior and learning during adolescence, yet it is unclear how the rise in gonadal hormones at puberty impacts the function of these systems. We studied the impact of prepubertal gonadectomy (GDX) on later evoked dopamine release in male Mus spicilegus , a mouse whose adolescent life history has been carefully characterized in the wild and laboratory. To examine how puberty impacts dopamine neuron function in M. spicilegus males, we removed the gonads prepubertally at postnatal day (P)25 and then examined evoked dopamine release in the dorsomedial, dorsolateral (DLS), and nucleus accumbens core regions of striatal slices at P60–70 (late adolescence/early adulthood). To measure dopamine release, we used near-infrared catecholamine nanosensors which enable study of spatial distribution of dopamine release. We found that prepubertal GDX led to a significantly reduced density of dopamine release sites and reduced dopam...

Alpha peak frequency (APF) is defined as a prominent spectral peak within the 8–12 Hz frequency range. Typically, an individual's alpha frequency is regarded as a stable neurophysiological marker. A wealth of recent evidence, however, indicates that APF shifts within short timescales in relation to task demands and even spontaneously so. Further, brain stimulation studies often report shifts in APF both within and between experimental sessions, directly contradicting the idea of a stable APF. To characterize the nonstationarities in spectral parameters, we estimated APFs from 1 s epochs of resting-state magnetoencephalography (MEG) recordings from healthy adults of either sex. To enhance signal-to-noise ratio, without compromising on temporal resolution, we averaged power spectra within parcelled regions. Our findings indicate that variation in APFs exacerbates along the posterior-to-anterior cortical plane, i.e., from the occipital to the frontal cortices. Further, by comparisons with amplitude-matched si...

Autism spectrum disorder, schizophrenia, and bipolar disorder are neuropsychiatric conditions that manifest early in life with a wide range of phenotypes, including repetitive behavior, agitation, and anxiety ( [American Psychological Association, 2013][1]). While the etiology of these disorders is incompletely understood, recent data implicate a role for mitochondrial dysfunction ( [Norkett et al., 2017][2]; [Khaliulin et al., 2025][3]). Mitochondria translocate to intracellular compartments to support energetics and free-radical buffering; failure to achieve this localization results in cellular dysfunction ( [Picard et al., 2016][4]). Mitochondrial Rho-GTPase 1 ( Miro1 ) resides on the outer mitochondrial membrane and facilitates microtubule-mediated mitochondrial motility ( [Fransson et al., 2003][5]). The loss of MIRO1 is reported to contribute to the onset/progression of neurodegenerative diseases, including amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease ( [Kay et al., 20...

The life cycle of the model nematode Caenorhabditis elegans involves a choice between two alternative developmental trajectories. Hermaphroditic larvae can either become reproductive adults or, under conditions of crowding or low food availability, enter a long-term, stress-resistant diapause known as the dauer stage. Chemical signals from a secreted larval pheromone promote the dauer trajectory in a concentration-dependent manner, and their influence can be antagonized by increased availability of a microbial food source. The decision is known to be under neuronal control, involving both sensory and interneurons. However, little is known about the dynamics of the underlying circuit, and the circuit mechanisms by which short-term fluctuations in the ratio of food and pheromone experienced by individual larvae are remembered and averaged over several hours. To investigate this, we quantitatively characterized the neuronal responses to food and pheromone inputs by measuring calcium traces from ASI and AIA ne...

Sulf1 is an extracellular sulfatase that regulates cell signaling by removing 6- O -sulfates from heparan sulfate. Although the roles of Sulf1 in neural development have been studied extensively, its functions in the adult brain remain largely unknown. Here, we report the effects of Sulf1 disruption on the neuronal properties of the medium spiny neurons (MSNs) in the nucleus accumbens (NAc) shell, one of the regions highly expressing Sulf1 . We separately labeled MSNs expressing dopamine D1 receptors (D1-MSNs) or D2 receptors (D2-MSNs) by injecting adult male Drd1-Cre and Drd2-Cre mice with a Cre-dependent AAV vector expressing a red fluorescent protein, mCherry, and examined their electrophysiological properties by means of whole-cell patch–clamp recording. In the D2-MSNs, Sulf1 disruption led to drastic changes in neural firing responses to depolarizing current injections: in the Sulf1 knock-out mice, the rheobase was smaller than in the wild-type mice, but the number of action potentials elicited by dep...