Specific groups have historically been, and continue to be, underrepresented in the biomedical research workforce, especially academia. Career choice is a multifactorial process that evolves over time; among all trainees, expressed interest in faculty research careers decreases over time in graduate school, but that trend is amplified in women and members of historically underrepresented racial and ethnic groups ([Golde and Dore, 2004][1]; [Fuhrmann et al., 2011][2]; [Sauermann and Roach, 2012][3]; [Gibbs et al., 2014][4]; [Roach and Sauermann, 2017][5]). This work was designed to investigate how career interest changes over time among recent neuroscience PhD graduates, and whether differences in career interests are associated with social identity, experiences in graduate school and postdoctoral training, and personal characteristics. We report results from a survey of 1479 PhD neuroscientists (including 16% underrepresented scientists and 54% women scientists). We saw repeated evidence that individual pr...

The entorhinal cortex (EC) is especially vulnerable in the early stages of Alzheimer’s disease (AD). In particular, cognitive deficits have been linked to alterations in the upper layers of EC. In the present report, we examined Layers II and III from eight human brain autopsies (four subjects with no recorded neurologic alterations and four AD cases). We used stereological methods to assess cortical atrophy of the EC and possible changes in the volume occupied by different cortical elements (neuronal and glial cell bodies; blood vessels; and neuropil). We performed 3D ultrastructural analyses of synapses using focused ion beam/scanning electron microscopy (FIB/SEM) to examine possible alterations related to AD. At the light microscope level, we found a significantly lower volume fraction occupied by neuronal bodies in Layer III and a higher volume fraction occupied by glial cell bodies in Layer II in AD cases. At the ultrastructural level, we observed that (1) there was a significantly lower synaptic dens...

Dravet syndrome (DS) is a developmental and epileptic encephalopathy with an increased incidence of sudden death. Evidence of interictal breathing deficits in DS suggests that alterations in subcortical projections to brainstem nuclei may exist, which might be driving comorbidities in DS. The aim of this study was to determine whether a subcortical structure, the bed nucleus of the stria terminalis (BNST) in the extended amygdala, is activated by seizures, exhibits changes in excitability, and expresses any alterations in neurons projecting to a brainstem nucleus associated with respiration, stress response, and homeostasis. Experiments were conducted using F1 mice generated by breeding 129.Scn1a+/− mice with wild-type C57BL/6J mice. Immunohistochemistry was performed to quantify neuronal c- fos activation in DS mice after observed spontaneous seizures. Whole-cell patch-clamp and current-clamp electrophysiology recordings were conducted to evaluate changes in intrinsic and synaptic excitability in the BNST...

Chronic vagus nerve stimulation (VNS) has been shown to facilitate learning, but effects of acute VNS on neural coding and behavior remain less well understood. Ferrets implanted with cuff electrodes on the vagus nerve were trained by classical conditioning on an auditory tone frequency-reward association. One tone was associated with reward while another tone was not. Tone frequencies and reward associations were changed every 2 d, requiring learning of a new relationship. When tones were paired with VNS, animals consistently learned the new association within 2 d. When VNS occurred randomly between trials, learning within 2 d was unreliable. In passively listening animals, neural activity in primary auditory cortex (A1) and pupil size were recorded before and after acute VNS-tone pairing. After pairing with a neuron’s best-frequency (BF) tone, responses by a subpopulation of neurons were reduced. VNS paired with an off-BF tone or during intertrial intervals had no effect. The BF-specific reduction in neu...

Restoration of lost function following a nervous system injury is limited in adulthood as the regenerative capacity of nervous system declines with age. Pharmacological approaches have not been very successful in alleviating the consequences of nervous system injury. On the contrary, physical activity and rehabilitation interventions are often beneficial to improve the health conditions in the patients with neuronal injuries. Using touch neuron circuit of Caenorhabditis elegans , we investigated the role of physical exercise in the improvement of functional restoration after axotomy. We found that a swimming session of 90 min following the axotomy of posterior lateral microtubule (PLM) neuron can improve functional recovery in larval and adult stage animals. In older age, multiple exercise sessions were required to enhance the functional recovery. Genetic analysis of axon regeneration mutants showed that exercise-mediated enhancement of functional recovery depends on the ability of axon to regenerate. Exer...

Naltrexone is an opioid receptor antagonist approved for the treatment of alcohol and opioid use disorders at doses of 50–150 mg/d. Naltrexone has also been prescribed at much lower doses (3–6 mg/d) for the off-label treatment of inflammation and pain. Currently, a compelling mechanistic explanation for the reported efficacy of low-dose naltrexone (LDN) is lacking and none of the proposed mechanisms can explain patient reports of improved mood and sense of well-being. Here, we examined the possibility that LDN might alter the activity of the endogenous opioid system involving proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARH) in male and female mice. Known actions of POMC neurons could account for changes in pain perception and mood. However, using electrophysiologic, imaging and peptide measurement approaches, we found no evidence for such a mechanism. LDN did not change the sensitivity of opioid receptors regulating POMC neurons, the production of the β-endorphin precurso...

Dynamic control of protein degradation via the ubiquitin proteasome system (UPS) is thought to play a crucial role in neuronal function and synaptic plasticity. The proteasome subunit Rpt6, an AAA ATPase subunit of the 19S regulatory particle (RP), has emerged as an important site for regulation of 26S proteasome function in neurons. Phosphorylation of Rpt6 on serine 120 (S120) can stimulate the catalytic rate of substrate degradation by the 26S proteasome and this site is targeted by the plasticity-related kinase Ca2+/calmodulin-dependent kinase II (CaMKII), making it an attractive candidate for regulation of proteasome function in neurons. Several in vitro studies have shown that altered Rpt6 S120 phosphorylation can affect the structure and function of synapses. To evaluate the importance of Rpt6 S120 phosphorylation in vivo , we created two mouse models which feature mutations at S120 that block or mimic phosphorylation at this site. We find that peptidase and ATPase activities are upregulated in the p...

Environmental cues attain the ability to guide behavior via learned associations. As predictors, cues can elicit adaptive behavior and lead to valuable resources (e.g., food). For some individuals, however, cues are transformed into incentive stimuli and elicit motivational states that can be maladaptive. The goal-tracker (GT)/sign-tracker (ST) animal model captures individual differences in cue-motivated behaviors, with reward-associated cues serving as predictors of reward for both phenotypes but becoming incentive stimuli to a greater degree for STs. While these distinct phenotypes are characterized based on Pavlovian conditioned approach (PavCA) behavior, they exhibit differences on a number of behaviors relevant to psychopathology. To further characterize the neurobehavioral endophenotype associated with individual differences in cue-reward learning, neuroendocrine and behavioral profiles associated with stress and anxiety were investigated in male GT, ST, and intermediate responder (IR) rats. It was ...

Environmental enrichment (EE) is beneficial to sensory functions. Thus, elucidating the neural mechanism underlying improvement of sensory stimulus discrimination is important for developing therapeutic strategies. We aim to advance the understanding of such neural mechanism. We found that tactile enrichment improved tactile stimulus feature discrimination. The neural correlate of such improvement was revealed by analyzing single-cell information coding in both the primary somatosensory cortex and the premotor cortex of awake behaving animals. Our results show that EE enhances the decision-information coding capacity of cells that are tuned to adjacent whiskers, and of premotor cortical cells.

Sex hormone levels continuously fluctuate across the reproductive cycle, changing the activity of neuronal circuits to coordinate female behavior and reproductive capacity. The ventrolateral division of the ventromedial hypothalamus (VMHvl) contains neurons expressing receptors for sex hormones and its function is intimately linked to female sexual receptivity. However, recent findings suggest that the VMHvl is functionally heterogeneous. Here, we used whole recordings and intracellular labeling to characterize the electrophysiological and morphologic properties of individual VMHvl neurons in naturally cycling females and report the existence of multiple electrophysiological phenotypes within the VMHvl. We found that the properties of progesterone receptor expressing (PR+) neurons, but not PR– neurons, depended systematically on the neuron’s location along the anterior-posterior (AP) axis of the VMHvl and the phase within the reproductive cycle. Prominent among this, the resting membrane potential of anter...