Alpha (8–12 Hz) oscillations and default mode network (DMN) activity dominate the brain's intrinsic activity in the temporal and spatial domains, respectively. They are thought to play crucial roles in the spatiotemporal organization of the complex brain system. Relatedly, both have been implicated, often concurrently, in diverse neuropsychiatric disorders, with accruing electroencephalogram (EEG)/magnetoencephalogram and functional magnetic resonance imaging (fMRI) data linking these two neural activities both at rest and during key cognitive operations. Prominent theories and extant findings thus converge to suggest a mechanistic relationship between alpha oscillations and the DMN. Here, we leveraged simultaneous EEG–fMRI data acquired before and after alpha-frequency transcranial alternating current stimulation ( α -tACS) and observed that α -tACS tightened the dynamic coupling between spontaneous fluctuations in alpha power and DMN connectivity (especially, in the posterior DMN, between the posterior c...

Mitral cells (MCs) and tufted cells (TCs) in the olfactory bulb (OB) act as an input convergence hub and transmit information to higher olfactory areas. Since first characterized, they have been classed as distinct projection neurons based on size and location: laminarly arranged MCs with a diameter larger than 20 µm in the mitral layer (ML) and smaller TCs spread across both the ML and external plexiform layers (EPL). Recent in vivo work has shown that these neurons encode complementary olfactory information, akin to parallel channels in other sensory systems. Yet, many ex vivo studies still collapse them into a single class, mitral/tufted, when describing their physiological properties and impact on circuit function. Using immunohistochemistry and whole-cell patch–clamp electrophysiology in fixed or acute slices from adult mice, we attempted to align in vivo and ex vivo data and test a soma size-based classifier of bulbar projection neurons using passive and intrinsic firing properties. We found that the...

Humans and nonhumans alike often make choices to gain information, even when the information cannot be used to change the outcome. Prior research has shown that the anterior cingulate cortex (ACC) is important for evaluating options involving reward-predictive information. Here we studied the role of ACC in information choices using optical inhibition to evaluate the contribution of this region during specific epochs of decision-making. Rats could choose between an uninformative option followed by a cue that predicted reward 50% of the time versus a fully informative option that signaled outcomes with certainty but was rewarded only 20% of the time. Reward seeking during the informative S+ cue decreased following ACC inhibition, indicating a causal contribution of this region in supporting reward expectation to a cue signaling reward with certainty. Separately in a positive control experiment and in support of a known role for this region in sustaining high-effort behavior for preferred rewards, we observe...

How humans achieve such a high degree of prosocial behavior is a subject of considerable interest. Exploration of the neural foundations of human prosociality has garnered significant attention in recent decades. Nevertheless, the neural mechanisms underlying human prosociality remain to be elucidated. To address this knowledge gap, we analyzed multimodal brain imaging data and data from 15 economic games. The results revealed several significant associations between brain characteristics and prosocial behavior, including stronger interhemispheric connectivity and larger corpus callosum volume. Greater functional segregation and integration, alongside fewer myelin maps combined with a thicker cortex, were linked to prosocial behavior, particularly within the social brain regions. The current study demonstrates that these metrics serve as brain markers of human prosocial behavior and provides novel insights into the structural and functional brain basis of human prosocial behavior.

Electrophysiology recordings from the brain using laminar multielectrode arrays allow researchers to measure the activity of many neurons simultaneously. However, laminar microelectrode arrays move relative to their surrounding neural tissue for a variety of reasons, such as pulsation, changes in intracranial pressure, and decompression of neural tissue after insertion. Inferring and correcting for this motion stabilizes the recording and is critical to identify and track single neurons across time. Such motion correction is a preprocessing step of standard spike-sorting methods. However, estimating motion robustly and accurately in electrophysiology recordings is challenging due to the stochasticity of the neural data. To tackle this problem, we introduce MEDiCINe ( M otion E stimation by Di stributional C ontrastive I nference for Ne urophysiology), a novel motion estimation method. We show that MEDiCINe outperforms existing motion estimation methods on an extensive suite of simulated neurophysiology rec...

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...

Maintenance of normal structure of the enteric nervous system (ENS), which regulates key gastrointestinal functions, requires robust homeostatic mechanisms, since by virtue of its location within the gut wall, the ENS is subject to constant mechanical, chemical, and biological stressors. Using transgenic and thymidine analog-based experiments, we previously discovered that neuronal turnover—where continual neurogenesis offsets ongoing neuronal loss at steady state—represents one such mechanism. Although other studies confirmed that neuronal death continues into adulthood in the myenteric plexus of the ENS, the complicated nature of thymidine analog presents challenges in substantiating the occurrence of adult neurogenesis. Therefore, it is vital to employ alternative, well-recognized techniques to substantiate the existence of adult enteric neurogenesis in the healthy gut. Here, by using established methods of assessing nuclear DNA content and detecting known mitotic marker phosphor-histone H3 (pH3) in Hu+...

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...

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...

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...