Neural signals necessary for gaze holding are produced in the excitatory networks of oculomotor neural integrators including the prepositus hypoglossi nucleus (PHN) and the interstitial nucleus of Cajal (INC). Our previous studies have shown that the activation of the networks can be evaluated by sustained excitatory postsynaptic current (EPSC) responses in vitro, in which a higher EPSC frequency after burst stimulation (100 Hz, 20 trains) than the frequency before the stimulation lasts for >1 s. Both the PHN and the INC receive serotonergic inputs mainly from the dorsal raphe nucleus, and serotonin (5-HT) induces depolarizing responses via 5-HT2 or 5-HT3 receptors and hyperpolarizing responses via 5-HT1A receptors in PHN and INC neurons. However, how 5-HT affects sustained EPSC responses remains unknown. In this study, we investigated the effects of 5-HT on sustained EPSC responses using whole-cell recordings in brainstem slices obtained from rats of either sex. Compared with the control treatment, bath a...

Mice offer a wealth of opportunities for investigating brain circuits regulating multiple behaviors, largely due to their genetic tractability. Social behaviors are translationally relevant, considering both mice and humans are highly social mammals, and human social behavior disruptions are key symptoms of myriad neuropsychiatric disorders. Stresses related to social experiences are particularly influential in the severity and maintenance of neuropsychiatric disorders like anxiety disorders and trauma and stressor-related disorders. Yet, induction and study of social stress in mice has disproportionately focused on males, influenced heavily by their inherent territorial nature. Social target-instigated stress (i.e., defeat), while ethologically relevant, is quite variable and predominantly specific to males, making rigorous and sex-inclusive studies challenging. In pursuit of a controllable, consistent, high-throughput, and sex-inclusive method for social stress elicitation, we modified a paradigm to trai...

People with epilepsy may experience sudden death due to respiratory failure through mechanisms that are currently not well understood. Epilepsy causing mutations are thought to elicit seizures due to altered function of forebrain circuits, yet breathing is controlled largely by the brainstem. To investigate how altered forebrain activity could impact breathing, we examined respiratory and seizure phenotypes in a mouse epilepsy model with a forebrain-specific deletion of the phosphatase and tensin homolog ( Pten ) gene. Using chronic diaphragm electromyography and cortical electroencephalography, we monitored Pten conditional knock-out (PTEN–cKO) mice (six males and four females) and control littermates (six males and three females) continuously from preseizure onset through end-stage disease. PTEN–cKO mice develop spontaneous seizures that progress in frequency with age, accompanied by gradual changes in respiratory function, even during interictal periods. As seizure burden increases, PTEN–cKO mice experi...

Recent work showed unexpectedly large, daily modulation of intracellular chloride concentration ([Cl−]in) in cortical pyramidal cells, with consequences for GABAergic function and network excitability ( [Alfonsa et al., 2023][1]; [Pracucci et al., 2023][2]). One explanation for this [Cl−]in modulation is that it arises from variation in presynaptic drive. In that case, neuronal classes with similar synaptic inputs should show correlated changes in activity-dependent ionic redistribution. To examine this prediction, we performed in vivo, LSSm-ClopHensor imaging to measure [Cl−]in and pHin in populations of parvalbumin- (PV) and somatostatin (SST)-expressing interneurons in neocortical Layer 2/3 of male and female adult mice. Imaging was performed at zeitgeber time (ZT)5 and ZT17, when pyramidal cell [Cl−]in shows maximal divergence ( [Pracucci et al., 2023][2]). Interestingly, PV interneurons also showed large physiological [Cl−]in modulation between these times but out-of-phase with that in pyramidal cells...

RNA localization to neuronal axons and dendrites provides spatiotemporal control over gene expression to support synapse function. Neuronal messenger RNAs (mRNAs) localize as ribonucleoprotein particles (RNPs), commonly known as RNA granules, the composition of which influences when and where proteins are made. High-throughput sequencing has revealed thousands of mRNAs that localize to the hippocampal neuropil. Whether these mRNAs are spatially organized into common RNA granules or distributed as independent mRNAs for proper delivery to synapses is debated. Here, using highly multiplexed single-molecule fluorescence in situ hybridization (HiPlex smFISH) and colocalization analyses, we investigate the subcellular spatial distribution of 15 synaptic neuropil localized mRNAs in the male and female rodent hippocampus. We observed that these mRNAs are present in the neuropil as heterogeneously sized fluorescent puncta with spatial colocalization patterns that generally scale by neuropil mRNA abundance. Indeed, ...

The “sign-tracking” and “goal-tracking” model of individual variation in associative learning permits the identification of rats with different cue reactivity and predisposition to addiction-like behaviors. Certainly, compared with “goal-trackers” (GTs), “sign-trackers” (STs) show more susceptibility traits such as increased cue-induced “relapse” of drugs of abuse. Different cue- and reward-evoked patterns of activity in the nucleus accumbens (NAc) have been a hallmark of the ST/GT phenotype. However, it is unknown whether differences in the intrinsic neuronal properties of NAc medium spiny neurons (MSNs) in the core and shell subregions are also a physiological correlate of these phenotypes. We performed whole-cell slice electrophysiology in outbred male rats and found that STs exhibited the lowest excitability in the NAc core, with lower number of action potentials and firing frequency as well as a blunted voltage/current relationship curve in response to hyperpolarized potentials in both the NAc core an...

Decoding algorithms provide a powerful tool for understanding the firing patterns that underlie cognitive processes such as motor control, learning, and recall. When implemented in the context of a real-time system, decoders also make it possible to deliver feedback based on the representational content of ongoing neural activity. That, in turn, allows experimenters to test hypotheses about the role of that content in driving downstream activity patterns and behaviors. While multiple real-time systems have been developed, they are typically implemented with a compiled programming language, making them more difficult for users to quickly adapt for new experiments. Here we present a software system written in the widely used Python programming language to facilitate rapid experimentation. Our solution implements the state space based clusterless decoding algorithm for an online, real-time environment. The parallelized application processes neural data with temporal resolution of 6 ms and median computational...

The Society for Neuroscience hosted a live webinar on How to Prepare for, Defend Against, and Recover from Animal Rights Oppositional Efforts, which included moderator and Chair of SfN’s Animals in Research Committee Dr. Katalin Gothard, MD, PhD and panelists Dr. Eric Nestler, MD, PhD, Dr. Sharon Juliano, PhD, and Matthew Bailey, President of the National Association for Biomedical Research (NABR) and the Foundation for Biomedical Research (FBR).

RNA localization to neuronal axons and dendrites provides spatiotemporal control over gene expression to support synapse function. Neuronal messenger RNAs (mRNAs) localize as ribonucleoprotein particles (RNPs), commonly known as RNA granules, the composition of which influences when and where proteins are made. High-throughput sequencing has revealed thousands of mRNAs that localize to the hippocampal neuropil. Whether these mRNAs are spatially organized into common RNA granules or distributed as independent mRNAs for proper delivery to synapses is debated. Here, using highly multiplexed single molecule fluorescence in situ hybridization (HiPlex smFISH) and colocalization analyses, we investigate the subcellular spatial distribution of 15 synaptic neuropil localized mRNAs in the male and female rodent hippocampus. We observed that these mRNAs are present in the neuropil as heterogeneously sized fluorescent puncta with spatial colocalization patterns that generally scale by neuropil mRNA abundance. Indeed, ...

When Melissa Harrington started as an assistant professor at Delaware State University, a Historically Black institution, she had a keen appreciation of the potential for Historically Black Colleges and Universities (HBCUs) to enhance diversity in biomedical sciences. In her time at DSU, Dr. Harrington, has led the creation and growth of many programs designed to encourage underrepresented students to participate in research and support their academic success, but more can and should be done to increase opportunities for diverse students to participate in science. In this article, Drs. Melissa Harrington and Christine Charvet explain the challenges of and potential solutions for enhancing diversity in STEM fields.