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 ...

The prepositus hypoglossi nucleus (PHN), involved in horizontal gaze control, contributes to this function via cooperation with the vestibulocerebellum (VC). Furthermore, some PHN neurons have been observed to project to cerebellar regions outside the VC. We previously reported a neuronal population in the ventral caudal PHN that projects to lobules III–V of the anterior vermis or to the cerebellar hemispheric crus. Because the properties of these neurons have not been clarified, this study aimed to determine their localization, projections, and electrophysiological and morphological characteristics in male rats. Tracing experiments revealed that these neurons were clustered within the ventral caudal PHN, approximately between the bregma −12.72 and −12.00 mm, and did not project to the uvula/nodulus (UN), which is part of the VC. Whole-cell recordings and morphological experiments revealed that these PHN neurons exhibited high input capacitance, low input resistance, low-frequency firing, prominent voltage...

It has long been hypothesized that the nervous system uses the direction of gravity to align the various sensory systems when interacting with the external world. In line with this hypothesis, systematic drift in hand-path orientation was recently observed during targeted arm motions performed with eyes closed in weightlessness or, on Earth, for longitudinal movements in a supine posture. No such drift was observed in upright posture on Earth. But the precise conditions under which participants exhibit such drift, and the factors that influence the magnitude of the drift, are not yet known. The objective of our study was to investigate if the upright posture, by virtue of being at a biomechanical singularity induced by the force of gravity, represents a unique condition in which drift in hand-path orientation is prevented. Human participants (male and female) performed sequences of repeated point-to-point arm movements between two visual targets aligned with the longitudinal body axis, first with eyes open...

Animal behavior is crucial for understanding both normal brain function and dysfunction. To facilitate behavior analysis of mice within their home environments, we developed DeepEthoProfile, an open-source software powered by a deep convolutional neural network for efficient behavior classification. DeepEthoProfile requires no spatial cues for either training or processing and is designed to perform reliably under real laboratory conditions, tolerating variations in lighting and cage bedding. For data collection, we introduce EthoProfiler, a mobile cage rack system capable of simultaneously recording up to 10 singly housed mice. We used 36 h of manually annotated video data sampled in 5 min clips from a 48 h video database of 10 mice. This published dataset provides a reference that can facilitate further research. DeepEthoProfile achieved an overall classification accuracy of over 83%, comparable with human-level accuracy. The model also performed on par with other state-of-the-art solutions on another pu...

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.

We have documented the early embryonic development of hypothalamic neurons expressing β-endorphin, α-melanocyte–stimulating hormone, neuropeptide Y, and kisspeptin in rhesus macaques, an animal model that is very similar to humans. Neurons expressing both β-End and αMSH are the first to develop and are initially located in the lateral basal hypothalamus (LBH) as early as day 32–34 of gestation. By day 45 of gestation, these neurons have migrated into the medial basal hypothalamic (MBH) area as their final destination. NPY neurons within the ARH develop later and first appear at day 44 of fetal life, at which time a cluster of neurons is present within the ARH–MBH area. NPY neurons continue to be expressed within the ARH area at all of the later fetal ages analyzed. Similarly, kisspeptin neurons develop later compared with β-End, although only a few cells are present in the ARH by day 44 of gestation, at which time kisspeptin is also expressed in the developing anterior lobe of the pituitary. By day 70 of g...

Early childhood is a critical period showing experience-dependent changes in brain structure and function. The complex link between the structural connectivity (SC) and functional connectivity (FC) of the brain is of particular interest. However, its relationship with both age and attention in early childhood is not well understood. In this study, children between the ages of 4 and 7, and at a 1 year follow-up visit, underwent neuroimaging (diffusion-weighted and passive-viewing functional magnetic resonance imaging) and assessments for selective, sustained, and executive attention. We examined regional graph metrics and SC–FC coupling of the structural and functional networks. Partial least squares was used to investigate longitudinal brain measure changes and cross-sectional associations with age and attention. We observed longitudinal changes in functional graph metrics and age-related decreases in SC modularity. Region-wise graph analyses revealed variable brain–behavior relationships across the brain,...

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...

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 ...