The mouse vomeronasal system controls several social behaviors. Pheromones and other social cues are detected by sensory neurons in the vomeronasal organ (VNO). Stimuli activate a transduction cascade that leads to membrane potential depolarization, increase in cytosolic Ca2+ level, and increased firing. The Ca2+-activated chloride channels TMEM16A and TMEM16B are co-expressed within microvilli of vomeronasal neurons, but their physiological role remains elusive. Here, we investigate the contribution of each of these channels to vomeronasal neuron firing activity by comparing wild-type (WT) and knock-out (KO) mice. Performing loose-patch recordings from neurons in acute VNO slices, we show that spontaneous activity is modified by Tmem16a KO, indicating that TMEM16A, but not TMEM16B, is active under basal conditions. Upon exposure to diluted urine, a rich source of mouse pheromones, we observe significant changes in activity. Vomeronasal sensory neurons (VSNs) from Tmem16a cKO and Tmem16b KO mice show short...

Retinoic acid (RA), a metabolite of vitamin A, has many physiological functions, and mounting evidence points to important roles in cognition. In vitro experiments indicate that RA is involved in homeostatic synaptic scaling in the hippocampus, which supports overall network stability during learning. It has been previously determined that disrupted RA signaling in the hippocampus causes deterioration of memory, that RA signaling declines with age in brain, and that application of RA reverses this decline. Here, we explore whether RA signaling is altered in an animal model of neurocognitive aging. We used a Morris water maze protocol to study cognitive decline in aged rats, which assesses hippocampus-dependent spatial memory and reveals substantial interindividual differences in aged animals. Aged unimpaired (AU) rats perform on par with young (Y), while aged impaired (AI) animals exhibit spatial memory deficits. We show that the major substrate for RA, retinol binding protein 4 (RBP4), is decreased in AU ...

Treatment options for cerebral infarction beyond the time window of reperfusion therapy are limited, and novel approaches are needed. PDGF-B is considered neuroprotective; however, it is difficult to administer at effective concentrations to infarct areas. Nanoparticles (NPs) are small and stable; therefore, we modified PDGF-B to the surface of naturally occurring heat shock protein NPs (HSPNPs) to examine its therapeutic effect in cerebral infarction. PDGF-B modified HSPNPs (PDGF-B HSPNPs) were injected 1 d after transient middle cerebral artery occlusion (t-MCAO) in CB-17 model mice. We analyzed the infarct volume and motor functional recovery at 3 and 7 d. PDGF-B HSPNPs were specifically distributed in the infarct area, and compared with HSPNPs alone, they significantly reduced infarct volumes and improved neurologic function 3 and 7 d after administration. PDGF-B HSPNP administration was associated with strong phosphorylation of Akt in infarct areas and significantly increased neurotrophin (NT)-3 produ...

Highlighted Research Paper: [[Tracking Mitochondrial Density and Positioning along a Growing Neuronal Process in Individual C. elegans Neuron Using a Long-Term Growth and Imaging Microfluidic Device by Sudip Mondal, Jyoti Dubey, Anjali Awasthi, Guruprasad Reddy Sure, Amruta Vasudevan, and Sandhya P. Koushika.][2]][2] []: /lookup/doi/10.1523/ENEURO.0360-20.2021

The brain’s connectome has a great impact on its function, as its structure affects the speed and efficiency of information transfer. As a highly energy-consuming organ, an efficient network structure is essential. A previous study has shown consistent overall brain connectivity across a large variety of species. This connectivity conservation was explained by a balance between inter and intra hemispheric connections, that is – spices with highly connected hemispheres appear to have weaker inter-hemisphere connections. This study examines this connectivity trade-off in the human brain using diffusion-based tractography and network analysis in the Human Connectome Project (970 subjects, 527 F). We explore the biological origins of this phenomenon, and heritability and effect on cognitive measures. The proportion of commissural fibers in the brain had a negative correlation to hemispheric efficiency, pointing to a trade-off between inner and inter hemispheric connectivity. Network hubs including anterior an...

When discussing procedural learning, it is now routine to consider both online and offline influences for skill acquisition. This is because it is commonly assumed that the evolution of a novel skill memory continues well after practice is over. Indeed, factors impacting offline contributions to skill memory development such as sleep and exercise have garnered considerable research interest in recent years. This is partly due to their capacity to foster post-practice consolidation, a process that has been identified as critical to moving a skill memory from a labile to more stable or elaborate form. While uncovering the potency of non-practice factors to facilitate consolidation is undoubtedly important, the present opinion is designed to remind the reader that a practice schedule, organized to challenge the learner, can, in and of itself, be effective in supporting consolidation resulting in significant gains in long-term skill retention. Significance Statement Adopting “best practices” is an objective...

Savings have been described as the ability of healthy humans to relearn a previously acquired motor skill faster than the first time, which in the context of motor adaptation suggests that the learning rate in the brain could be adjusted when a perturbation is recognized. Alternatively, it has been argued that apparent savings were the consequence of a distinct process that instead of reflecting a change in the learning rate, revealed an explicit re-aiming strategy. Based on recent evidence that feedback adaptation may be central to both planning and control, we hypothesized that this component could genuinely accelerate relearning in human adaptation to force fields during reaching. Consistent with our hypothesis, we observed that upon re-exposure to a previously learned force field, the very first movement performed by healthy volunteers in the relearning context was better adapted to the external disturbance, and this occurred without any anticipation or cognitive strategy because the relearning session...

Galanin, one of the most inducible neuropeptides, is widely present in developing brains, and its expression is altered by pathological events (such as epilepsy, ischemia and axotomy). The roles of galanin in brain development under both normal and pathological conditions have been hypothesized, but the question of how galanin is involved in fetal and early postnatal brain development remains largely unanswered. In this study, using granule cell migration in the cerebellum of early postnatal mice (both sexes) as a model system, we examined the role of galanin in neuronal cell migration during normal development and after brain injury. Here we show that during normal development, endogenous galanin participates in accelerating granule cell migration via altering the Ca2+ and cAMP signaling pathways. Upon brain injury induced by the application of cold insults, galanin levels decrease at the lesion sites, but increase in the surroundings of lesion sites. Granule cells exhibit corresponding changes in migrati...

Recent large genome-wide association studies (GWAS) have identified multiple confident risk loci linked to addiction-associated behavioral traits. Most genetic variants linked to addiction-associated traits lie in non-coding regions of the genome, likely disrupting cis-regulatory element (CRE) function. CREs tend to be highly cell type-specific and may contribute to the functional development of the neural circuits underlying addiction. Yet, a systematic approach for predicting the impact of risk variants on the CREs of specific cell populations is lacking. To dissect the cell types and brain regions underlying addiction-associated traits, we applied stratified LD score regression to compare GWAS to genomic regions collected from human and mouse assays for open chromatin, which is associated with CRE activity. We found enrichment of addiction-associated variants in putative CREs marked by open chromatin in neuronal (NeuN+) nuclei collected from multiple prefrontal cortical areas and striatal regions known ...

Exposure to loud noises not only leads to trauma and loss of output from the ear, but also alters downstream central auditory circuits. A perceptual consequence of noise-induced central auditory disruption is impairment in gap-induced prepulse inhibition, also known as gap detection. Recent studies have implicated cortical parvalbumin-positive (PV) inhibitory interneurons in gap detection and prepulse inhibition. Here we show that exposure to loud noises specifically reduces the density of cortical PV but not somatostatin-positive (SOM) interneurons in the primary auditory cortex (AI) in mice (C57BL/6) of both sexes. Optogenetic activation of PV neurons produced less cortical inhibition in noise-exposed than sham-exposed animals, indicative of reduced PV neuron function. Activation of SOM neurons resulted in similar levels of cortical inhibition in noise- and sham-exposed groups. Furthermore, chemogenetic activation of PV neurons with the hM3-based DREADD (designer receptor exclusively activated by designe...