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...

Delayed motor development is an early clinical sign of fetal alcohol spectrum disorders. However, changes at the neural circuit level that underlie early motor differences are underexplored. The striatum, the principal input nucleus of the basal ganglia, plays an important role in motor learning in adult animals, and the maturation of the striatal circuit has been associated with the development of early motor behaviors. Here, we briefly exposed pregnant C57BL/6 dams to ethanol (5% w/w) in a liquid diet on embryonic days 13.5–16.5 and assessed the mouse progeny using a series of nine brief motor behavior tasks on postnatal days 2–14. Live brain slices were then obtained from behaviorally tested mice for whole-cell voltage- and current-clamp electrophysiology to assess GABAergic/glutamatergic synaptic activity and passive/active properties in two populations of striatal neurons: GABAergic interneurons and spiny striatal projection neurons. Electrophysiologically recorded spiny striatal projection neurons we...

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 ...

In the article “Comprehensive Characterization of a Subfamily of Ca2+-Binding Proteins in Mouse and Human Retinal Neurons at Single-Cell Resolution” by Jun-Bin Liu, He-Lan Yuan, Gong Zhang, and Jiang-Bin Ke …

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...

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.

Neuroligins (NLGNs) are a family of postsynaptic adhesion molecules that bind to their presynaptic partners, neurexins, facilitating the formation and maintenance of synapses. In humans, there are five genes encoding NLGNs ( NLGN1-3 , NLGN4X , and NLGN4Y ), with NLGN1-3 having highly conserved counterparts in rodents, allowing these genes to be studied with high confidence of translational validity in mouse models. Human NLGN4X and 4Y were often assumed to serve similar functions because they share a 97% sequence homology, whereas mouse NLGN4-like is quite divergent. Many NLGN-mediated synaptic effects are modulated through post-translation modifications, which exert temporal and spatial control. In this report, we characterize a conserved phosphorylation site, serine 712, on NLGN4X and 4Y. Despite serine 712 being located in a highly conserved region between NLGN4X and 4Y, we observed kinase specificity. PKA exclusively phosphorylates NLGN4X S712, whereas Cdk5 phosphorylates S712 on both NLGN4X and 4Y. NL...

Epilepsy, affecting millions globally, often leads to significant cognitive and psychiatric comorbidities, particularly in children. Anxiety and depression are particularly prevalent, with roughly a quarter of pediatric epilepsy patients having a comorbid diagnosis. Current treatments inadequately address these issues. Adrenocorticotropic hormone (ACTH), a melanocortin peptide, has shown promise in mitigating deficits after early-life seizures (ELS), potentially through mechanisms beyond its canonical action on the melanocortin 2 receptor. This study explores the hypothesis that recurrent ELS is associated with long-term anxiety and that treatment with ACTH can prevent this anxiety through a mechanism that involves the melanocortin 4 receptor (MC4R) in the brain. Our findings reveal that ACTH ameliorates anxiety-like behavior associated with ELS, without altering seizure parameters, in wild-type but not in male and female MC4R knock-out mice. Our findings also show that knocking-in MC4R in either neurons o...