Humans exhibit laterality preferences, with handedness being the most extensively studied. Accordingly, brain–handedness associations are well documented. However, laterality preferences extend beyond handedness to include other limbs, such as footedness and eyedness. Despite these distinctions, brain–footedness and brain–eyedness associations using resting-state functional connectomes remain largely unexplored. We utilize two large datasets, the Human Connectome Project-Development (HCP-D) and Human Connectome Project-Aging (HCP-A), to study the associations between sidedness (i.e., handedness, footedness, and eyedness) and whole-brain functional connectomes. While hand and foot preferences were correlated significantly, they explained <40% of the variance, suggesting some distinctions between measures. For both cohorts, significant associations between handedness connectivity were observed [ p  < 0.05, network-based statistics (NBS) corrected]. Notable patterns include increased connectivity for left-han...

Neuroimaging data reveal that a functional locus ceruleus-noradrenaline (LC-NA) system is critical in maintaining cognitive performance during aging. However, older adults show reduced LC integrity and altered functional connectivity, demonstrating both structural declines and dysfunction. The LC-NA system mediates mechanisms of attention processing and eye tracking studies have shown that older adults are slower and more distractible compared with young adults in visual search tasks. Prior studies have shown that mindfulness meditation modulates LC noradrenergic activity, increases gray matter volume in the brainstem, and improves attentional control. Thus, in a preregistered longitudinal study, we investigated whether 30 d of guided mindfulness meditation using a mobile application improved attentional control measured with eye movements. We hypothesized that older adults would show greater benefits from the mindfulness intervention compared with young adults. In two oculomotor search tasks, we identifie...

The development of Schwann cells, which myelinate axons in the peripheral nervous system, is critically dependent on MEK/ERK signaling. While Ets-domain transcription factors ( Etv1 , Etv4 , Etv5 ) are downstream effectors of this pathway, only Etv1 has been specifically linked to Schwann cell development. Here, we examined the functions of Etv5 , which is expressed in Schwann cell precursors, neural crest cells and satellite glia, at embryonic stages and at low levels in mature Schwann cells. In hypomorphic Etv5tm1Kmm homozygous mutant mice, no overt defects in Schwann cell differentiation were observed at embryonic stages. To study the function of Etv5 in juvenile (postnatal days 21–30) and mature adult (6 month) mice, we generated Etv5 conditional knock-outs (cKOs) using a Sox10-Cre driver. In juvenile male Etv5 -cKO mice, Schwann cell numbers increased normally after a peripheral nerve crush injury, a response that was attenuated by 6 months. Transmission electron microscopy of the naive sciatic nerve ...

There is a growing imperative to understand the neurophysiological impact of our rapidly changing and diverse technological, social, chemical, and physical environments. To untangle the multidimensional and interacting effects requires data at scale across diverse populations, taking measurement out of a controlled lab environment and into the field. Electroencephalography (EEG), which has correlates with various environmental factors as well as cognitive and mental health outcomes, has the advantage of both portability and cost-effectiveness for this purpose. However, with numerous field researchers spread across diverse locations, data quality issues and researcher idle time due to insufficient participants can quickly become unmanageable and expensive problems. In programs we have established in India and Tanzania, we demonstrate that with appropriate training, structured teams, and daily automated analysis and feedback on data quality, nonspecialists can reliably collect EEG data alongside various surv...

Advances in in vivo Ca2+ imaging using miniature microscopes have enabled researchers to study single-neuron activity in freely moving animals. Tools such as Minian and CalmAn have been developed to convert Ca2+ visual signals to numerical data, collectively referred to as CalV2N. However, substantial challenges remain in analyzing the large datasets generated by CalV2N, particularly in integrating data streams, evaluating CalV2N output quality, and reliably and efficiently identifying Ca2+ transients. In this study, we introduce CalTrig, an open-source graphical user interface (GUI) tool designed to address these challenges at the post-CalV2N stage of data processing collected from C57BL/6J mice. CalTrig integrates multiple data streams, including Ca2+ imaging, neuronal footprints, Ca2+ traces, and behavioral tracking, and offers capabilities for evaluating the quality of CalV2N outputs. It enables synchronized visualization and efficient Ca2+ transient identification. We evaluated four machine learning m...

The endocannabinoid (eCB) signaling system is robustly expressed in the cerebellum from embryonic developmental stages to adulthood. It plays a key role in regulating cerebellar synaptic plasticity and excitability, suggesting that impaired eCB signaling could lead to deficits in cerebellar adjustments of ongoing behaviors and cerebellar learning. Indeed, human mutations in DAGLα are associated with neurodevelopmental disorders. In this study, we show that selective deletion of the eCB synthesizing enzyme diacylglycerol lipase alpha (Daglα) from mouse cerebellar Purkinje cells (PCs) alters motor and social behaviors, disrupts short-term synaptic plasticity in both excitatory and inhibitory synapses, and reduces PC activity during social exploration. Our results provide the first evidence for cerebellar-specific eCB regulation of social behaviors and implicate eCB regulation of synaptic plasticity and PC activity as the neural substrates contributing to these deficits.

Neural circuits that consolidate sensory cues are essential for neurological functioning. Neural circuits that perform sensory integration can vary greatly because the sensory processing regions of the brain employ various neural motifs. Here, we investigate a neural circuit that mediates the response to conflicting stimuli in Caenorhabditis elegans . We concurrently expose animals to an aversive dispersal pheromone, osas#9, and an attractive bacterial extract. While worms usually avoid osas#9 alone, they suppress this avoidance behavior in the presence of a bacterial extract. Loss-of-function mutants and cell-specific rescues reveal that signaling from the ADF and NSM neurons is essential for bacterial extract-induced osas#9 avoidance attenuation. The inhibitory serotonin receptor, MOD-1, which is widely expressed on interneurons and motor neurons, is required for this sensory integration, suggesting that serotonin acts in an inhibitory manner. By performing calcium imaging on the ADF neurons in synaptic ...

Hippocampal sharp-wave ripples (SWRs) are critical events implicated in memory consolidation, planning, and the reactivation of recent experiences. Under freely moving conditions, a well-established dichotomy exists: hippocampal networks predominantly generate theta oscillations during periods of reward pursuit (preparatory behaviors) and exhibit pronounced SWR activity once the reward is achieved (consummatory behaviors). Here, it was examined how SWRs are modulated by reward delivery and small movements in head-fixed rats. Contrary to the canonical view established in freely moving settings, the results revealed that the dominant and more enduring effect was a sustained suppression of SWR activity immediately following water delivery. Moreover, even minor, localized movements (such as whisking or body adjustments) decreased SWR occurrence, demonstrating that hippocampal ripple generation is highly sensitive to motor engagement, irrespective of reward timing. Such movement-induced suppression of ripples p...

Hippocampal synaptic activity is tightly regulated to ensure appropriate synaptic function and plasticity, which are important for critical cognitive processes such as learning and memory. Altered hippocampal synaptic function can lead to cognitive and behavioral deficits observed in neurodegenerative diseases such as Alzheimer's disease (AD), necessitating a deeper fundamental understanding of hippocampal synaptic control mechanisms. Glycerophosphodiester phosphodiesterase 2 (GDE2 or GDPD5) is a surface transmembrane enzyme that cleaves the glycosylphosphatidylinositol anchor that tethers some proteins to the membrane. Mice lacking GDE2 ( Gde2 KO) display behavioral deficits in learning and memory that are hippocampal-dependent. However, roles of GDE2 in mouse hippocampal function are not known. Here, we show that GDE2 is expressed in pre- and postsynaptic compartments along apical dendrites in hippocampal CA1 cells. Gde2 KO CA1 cells showed increased dendritic length and complexity and increased numbers ...

Previous research suggests that stress predisposes individuals to develop substance use disorders by disrupting the brain processing of rewards. Yet, how stressful experiences disrupt the brain processing of reward-related cues at the neuronal level is poorly understood. Intermittent social defeat (ISD) is a stress animal model that increases reward-seeking behavior, drug self-administration, and choice impulsivity up to several weeks after stress. We tested the hypothesis that ISD disrupts the neuronal encoding of reward cues in key areas of the brain that regulate reward-seeking. We examined in vivo neuronal dynamics in response to reward cues in the dorsal medial prefrontal cortex (dmPFC) and the ventral tegmental area (VTA) simultaneously, and longitudinally, in control and stressed Long–Evans male rats during a discriminative stimulus reward-seeking task. In the dmPFC, ISD decreased cue-evoked neuronal activity 1 and 15 d after stress, which indicates a long-term degradation of outcome anticipation-re...