Self-administration of addictive substances like heroin can couple the rewarding/euphoric effects of the drug with drug-associated cues, and opioid cue reactivity contributes to relapse vulnerability in abstinent individuals recovering from an opioid use disorder (OUD). Opioids are reported to alter the intrinsic excitability of medium spiny neurons (MSNs) in the nucleus accumbens (NAc), a key brain reward region linked to drug seeking, but how opioids alter NAc MSN neuronal excitability and the impact of altered MSN excitability on relapse-like opioid seeking remain unclear. Here, we discovered that self-administered, but not experimenter-administered, heroin reduced NAc protein levels of the voltage-gated sodium channel auxiliary subunit, SCN1b, in male and female rats. Viral-mediated reduction of NAc SCN1b increased the intrinsic excitability of MSNs, but without altering glutamatergic and GABAergic synaptic transmission. While reducing NAc SCN1b levels had no effect on acquisition of heroin self-admini...

Zebrafish have gained prominence as a model organism in neuroscience over the past several decades, generating key insight into the development and functioning of the vertebrate brain. However, techniques for whole-brain mapping in adult stage zebrafish are lacking. Here, we describe a pipeline built using open-source tools for whole-brain activity mapping in adult zebrafish. Our pipeline combines advances in histology, microscopy, and machine learning to capture c-fos activity across the entirety of the brain. Following tissue clearing, whole-brain images are captured using light-sheet microscopy and registered to the recently created adult zebrafish brain atlas (AZBA) for automated segmentation. By way of example, we used our pipeline to measure brain activity after zebrafish were subject to the novel tank test, one of the most widely used behaviors in adult zebrafish. c-fos levels peaked 15 min following behavior and several regions, including those containing serotoninergic and dopaminergic neurons, we...

Anterior–posterior interactions in the alpha band (8–12 Hz) have been implicated in various functions including perception, attention, and working memory. The underlying neural communication can be flexibly controlled by adjusting phase relations when activities across anterior–posterior regions oscillate at a matched frequency. We thus investigated how alpha oscillation frequencies spontaneously converged along anterior–posterior regions by tracking oscillatory EEG activity while participants rested. As more anterior–posterior regions (scalp sites) frequency-converged, the probability of additional regions joining the frequency convergence increased, and so did oscillatory synchronization (i.e., oscillatory power) at participating regions, suggesting that anterior–posterior frequency convergences are driven by inter-regional entrainment. Notably, frequency convergences were accompanied by two types of approximately linear phase gradients, one progressively phase lagged in the anterior direction, the poste...

The annual Society for Neuroscience (SfN) meeting is a bonanza of scientific achievement: famous keynote speakers, beautiful scientific results, and award ceremonies. This focus is exciting and invigorating but glosses over the many failures, mistakes, and rejections that typically lead to scientific success. Our goal has been to create a space within the annual SfN meeting for open conversation about scientific failure and, by doing so, increase transparency, resilience, and mental well-being within our community. In this article, we share the materials that we have used at SfN during the past 4 years (2021–2024) to promote discussions of scientific failure, including formal storytelling, individual and interactive games, and confessionals. For each activity, we provide the rationale and practical guidance regarding logistics and usage. We hope this will aid scientists interested in adapting the activities for their own communities or local events. We end with a call for scientific institutions to commit ...

Cutaneomuscular reflexes (CMRs) can be recorded in the hand muscle of human subjects after stimulation of a digital nerve. We hypothesized that repeated synchronous stimulation of nerves from two digits may lead to long-term plastic changes in CMR, by the mechanisms of spike-timing–dependent plasticity (STDP). To test this idea, we conducted experiments in 27 healthy human volunteers. After baseline measurement of CMR, one of four 30-min-long stimulation conditions were tested; the CMR was then remeasured. The four conditions were simultaneous index finger and thumb stimulation; asynchronous index finger and thumb stimulation; thumb 5 ms before index finger stimulation; and thumb-only stimulation. Neither the early (E1) nor late excitatory (E2) components of the CMR showed consistent changes after any stimulation condition. The inhibitory (I1) component was slightly reduced in all cases. To understand why paired stimulation did not produce long-term changes, we conducted a further experiment. In this, we m...

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects 8–12% of children globally. Hyperactivity-related behaviors, as well as inattention and impulsivity, are regarded as the nuclear symptoms of ADHD. At present, its etiologies and risk factors are unknown. Previous research linked TARP γ-8 deficiency to ADHD-like behaviors in mice, including hyperactivity, impulsivity, and memory deficits. Aniracetam, a nootropic drug, enhances cognition by modulating cholinergic activity and glutamate receptors, offering neuroprotective effects. This study examined TARP γ-8 knockout (KO) mice at 4 and 8 weeks, assessing behaviors through locomotor activity, cliff avoidance, novel object recognition, and contextual fear conditioning tests. TARP γ-8 KO mice exhibited hyperactivity, reduced recognition memory, and impaired short-term memory and long-term memory. Aniracetam administration improved these behavioral deficits, suggesting its potential as a therapeutic agent for ADHD. The ...

While ketamine, an NMDA receptor antagonist, is effective in treating major depression, studies have not addressed the safety of repeated ketamine infusions in depressed patients with comorbid alcohol use disorder (AUD). In this study, we aimed to determine whether a history of chronic social isolation and alcohol exposure alter the reinforcing properties of ketamine in male and female rats. Rats were pair-housed or socially isolated for 12 weeks and underwent intermittent access to 20% alcohol. Subsequently, rats underwent intravenous ketamine self-administration under a fixed ratio 1 schedule, followed by extinction training and one session of cue-induced reinstatement. Dendritic spine morphology was examined in the nucleus accumbens, an important area implicated in reward and motivation. Our results show that females self-administered more ketamine than males, a history of alcohol increased ketamine intake in females, and a history of isolation or alcohol independently increased ketamine intake in males...

Alexander disease (AxD) is a rare neurological disorder caused by dominant gain-of-function mutations in the gene for glial fibrillary acidic protein. Expression of mutant protein results in astrocyte dysfunction that ultimately leads to developmental delay, failure to thrive, and intellectual and motor impairment. The disease is typically fatal, and at present there are no preventative or effective treatments. To gain a better understanding of the link between astrocyte dysfunction and behavioral deficits in AxD, we have recently developed a rat model that recapitulates many of the clinical features of the disease, including failure to thrive, motor impairment, and white matter deficits. In the present study, we show that both male and female AxD model rats exhibit a neurodegenerative profile with a progressive neuroinflammatory response combined with reduced expression of synaptic and mitochondrial proteins. Consistent with these results, AxD rats show reduced hippocampal long-term potentiation and are c...

Binocular disparity is used for perception and action in three dimensions. Neurons in the primary visual cortex respond to binocular disparity in random dot patterns, even when the contrast is inverted between eyes (false depth cue). In contrast, neurons in the ventral stream largely cease to respond to false depth cues. This study evaluated whether GABAergic inhibition is involved in suppressing false depth cues in the human ventral visual cortex. We compared GABAergic inhibition (GABA+) and glutamatergic excitation (Glx) during the viewing of correlated and anticorrelated binocular disparity in 18 participants using single-voxel proton magnetic resonance spectroscopy. Measurements were taken from the early visual cortex (EVC) and the lateral occipital cortex (LO). Three visual conditions were presented per voxel location: correlated binocular disparity, anticorrelated binocular disparity, or a blank gray screen with a fixation cross. To identify differences in neurochemistry, GABA+ or Glx levels were com...

The external globus pallidus (GPe) is a central part of the basal ganglia indirect pathway implicated in movement and decision-making. As a hub connecting the dorsal striatum and subthalamic nucleus (STN), the GPe guides repetitive and routine behaviors. However, it remains unknown how diverse GPe cells engage in routine formation while learning action sequences in repetitive reward-seeking conditioning. Here, in male mice, we investigated the Ca2+ dynamics of two GPe cell types, astrocytes and parvalbumin-expressing neurons, during routine formation. Our findings show that the dynamics of GPe astrocytes may be involved in action sequence refinement, a characteristic potentially contributing to more efficient reward-seeking behavior.