Geospatial Distribution of Obsessive-Compulsive Disorder Specialists: Understanding Access as a Function of Distance, Insurance Status, and Neighborhood Socioeconomic Status.

Obsessive-compulsive disorder is an impairing psychiatric condition affecting 1-2% of adults and youth. Cognitive-behavioral therapy with exposure and response prevention (CBT) is an efficacious intervention but requires specialty training and access is often limited. While certain factors are associated with treatment access, one key barrier that has not been explored is the geographic availability of OCD treatment providers.

Primary Outcomes for Adults Receiving the Unified Protocol after Hurricane Harvey in an Integrated Healthcare Setting.

The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) has demonstrated efficacy for treating anxiety and depression. However, there are limited effectiveness data when conducted in real-world settings with diverse populations, including those with trauma. We evaluated treatment outcomes in a naturalistic, community setting among 279 adults who received UP following Hurricane Harvey.

Sex Differences in the Epilepsies and Associated Comorbidities: Implications for Use and Development of Pharmacotherapies.

The epilepsies are common neurologic disorders characterized by spontaneous recurrent seizures. Boys, girls, men, and women of all ages are affected by epilepsy and, in many cases, by associated comorbidities as well. The primary courses of treatment are pharmacological, dietary, and/or surgical, depending on several factors, including the areas of the brain affected and the severity of the epilepsy.

A Single Test to Study Social Behavior and Repetitive Self-grooming in Mice.

The ability to recognize and interact with members of the same species is essential for social communication. Investigating the neural substrates of social interest and recognition may offer insights into the behavioral differences present in disorders affecting social behavior. Assays used to study social interest in rodents include the 3-chamber test, a partition test, and a social interaction test.

Estrous Cycle Monitoring in Mice with Rapid Data Visualization and Analysis.

The estrous cycle provides a readout of reproductive health in female laboratory rodents, and estrous cycle stage can be an important physiological variable. Accurate assessment of estrous cycle stage is also important in producing timed pregnancies for developmental studies. Here, we provide a protocol for evaluation of estrous cycle stage through a minimally invasive procedure of acquiring cells lining the vaginal cavity and immediate microscopic visual assessment of these cells without drying or staining.

Show Me the Meaning of Being Lonely (and Its Effects on Seizure Burden and Comorbidities).

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Nucleus-specific modulation of phasic and tonic inhibition by endogenous neurosteroidogenesis in the murine thalamus.

Neurosteroids are potent allosteric modulators of GABA receptors (GABA Rs). Although the effects of exogenous neurosteroids on GABA R function are well documented, less is known about effects of neurosteroids produced by local endogenous biosynthesis. The neurosteroidogenic enzymes 5α-reductase and 3α-hydroxysteroid dehydrogenase are expressed in two nuclei of somatosensory thalamus, the thalamic reticular nucleus (nRT) and ventrobasal nucleus (VB).

Inhibition Gets a New KAR Smell.

Ionotropic and metabotropic kainate receptor signaling regulates Cl homeostasis and GABAergic inhibition Garand D, Mahadevan V, Woodin MA. J Physiol. 2018.

Differential impacts on multiple forms of spatial and contextual memory in diazepam binding inhibitor knockout mice.

Learning and memory are fundamental processes that are disrupted in many neurological disorders including Alzheimer's disease and epilepsy. The hippocampus plays an integral role in these functions, and modulation of synaptic transmission mediated by γ-aminobutyric acid (GABA) type-A receptors (GABA Rs) impacts hippocampus-dependent learning and memory. The protein diazepam binding inhibitor (DBI) differentially modulates GABA Rs in various brain regions, including hippocampus, and changes in DBI levels may be linked to altered learning and memory.

Changes in Both Neuron Intrinsic Properties and Neurotransmission Are Needed to Drive the Increase in GnRH Neuron Firing Rate during Estradiol-Positive Feedback.

Central output of gonadotropin-releasing hormone (GnRH) neurons controls fertility and is sculpted by sex-steroid feedback. A switch of estradiol action from negative to positive feedback initiates a surge of GnRH release, culminating in ovulation. In ovariectomized mice bearing constant-release estradiol implants (OVX+E), GnRH neuron firing is suppressed in the morning (AM) by negative feedback and activated in the afternoon (PM) by positive feedback; no time-of-day-dependent changes occur in OVX mice.

Dynamic and Sex-Specific Changes in Gonadotropin-Releasing Hormone Neuron Activity and Excitability in a Mouse Model of Temporal Lobe Epilepsy.

Reproductive endocrine disorders are prominent comorbidities of temporal lobe epilepsy (TLE) in both men and women. The neural mechanisms underlying these comorbidities remain unclear, but hypothalamic gonadotropin-releasing hormone (GnRH) neurons may be involved. Here, we report the first direct demonstrations of aberrant GnRH neuron function in an animal model of epilepsy.

Subregion-Specific Impacts of Genetic Loss of Diazepam Binding Inhibitor on Synaptic Inhibition in the Murine Hippocampus.

Benzodiazepines are commonly prescribed to treat neurological conditions including epilepsy, insomnia, and anxiety. The discovery of benzodiazepine-specific binding sites on γ-aminobutyric acid type-A receptors (GABARs) led to the hypothesis that the brain may produce endogenous benzodiazepine-binding site ligands. An endogenous peptide, diazepam binding inhibitor (DBI), which can bind these sites, is thought to be capable of both enhancing and attenuating GABAergic transmission in different brain regions.

Regulation of Thalamic and Cortical Network Synchrony by Scn8a.

Voltage-gated sodium channel (VGSC) mutations cause severe epilepsies marked by intermittent, pathological hypersynchronous brain states. Here we present two mechanisms that help to explain how mutations in one VGSC gene, Scn8a, contribute to two distinct seizure phenotypes: (1) hypoexcitation of cortical circuits leading to convulsive seizure resistance, and (2) hyperexcitation of thalamocortical circuits leading to non-convulsive absence epilepsy. We found that loss of Scn8a leads to altered RT cell intrinsic excitability and a failure in recurrent RT synaptic inhibition.

Disrupted female estrous cyclicity in the intrahippocampal kainic acid mouse model of temporal lobe epilepsy.

Objective: Reproductive dysfunction is a comorbidity that commonly occurs with temporal lobe epilepsy (TLE). Characterization of this comorbidity in various models of TLE in mice will greatly facilitate mechanistic investigations of the relationship between reproductive disorders and seizures initiated in the hippocampus. Here we investigate the impact on female reproductive estrous cyclicity in the intrahippocampal kainic acid mouse model of TLE and demonstrate the utility of using this model for future mechanistic studies.

Feedback modulation of neural network synchrony and seizure susceptibility by Mdm2-p53-Nedd4-2 signaling.

Background: Neural network synchrony is a critical factor in regulating information transmission through the nervous system. Improperly regulated neural network synchrony is implicated in pathophysiological conditions such as epilepsy. Despite the awareness of its importance, the molecular signaling underlying the regulation of neural network synchrony, especially after stimulation, remains largely unknown.

Astrocytes potentiate GABAergic transmission in the thalamic reticular nucleus via endozepine signaling.

Emerging evidence indicates that diazepam-binding inhibitor (DBI) mediates an endogenous benzodiazepine-mimicking (endozepine) effect on synaptic inhibition in the thalamic reticular nucleus (nRT). Here we demonstrate that DBI peptide colocalizes with both astrocytic and neuronal markers in mouse nRT, and investigate the role of astrocytic function in endozepine modulation in this nucleus by testing the effects of the gliotoxin fluorocitrate (FC) on synaptic inhibition and endozepine signaling in the nRT using patch-clamp recordings. FC treatment reduced the effective inhibitory charge of GABAA receptor (GABAAR)-mediated spontaneous inhibitory postsynaptic currents in WT mice, indicating that astrocytes enhance GABAAR responses in the nRT.

Sniffer patch laser uncaging response (SPLURgE): an assay of regional differences in allosteric receptor modulation and neurotransmitter clearance.

Allosteric modulators exert actions on neurotransmitter receptors by positively or negatively altering the effective response of these receptors to their respective neurotransmitter. γ-Aminobutyric acid (GABA) type A ionotropic receptors (GABAARs) are major targets for allosteric modulators such as benzodiazepines, neurosteroids, and barbiturates. Analysis of substances that produce similar effects has been hampered by the lack of techniques to assess the localization and function of such agents in brain slices.

Endogenous positive allosteric modulation of GABA(A) receptors by diazepam binding inhibitor.

Benzodiazepines (BZs) allosterically modulate γ-aminobutyric acid type-A receptors (GABAARs) to increase inhibitory synaptic strength. Diazepam binding inhibitor (DBI) protein is a BZ site ligand expressed endogenously in the brain, but functional evidence for BZ-mimicking positive modulatory actions has been elusive. We demonstrate an endogenous potentiation of GABAergic synaptic transmission and responses to GABA uncaging in the thalamic reticular nucleus (nRT) that is absent in both nm1054 mice, in which the Dbi gene is deleted, and mice in which BZ binding to α3 subunit-containing GABAARs is disrupted.

Focal cortical infarcts alter intrinsic excitability and synaptic excitation in the reticular thalamic nucleus.

Focal cortical injuries result in death of cortical neurons and their efferents and ultimately in death or damage of thalamocortical relay (TCR) neurons that project to the affected cortical area. Neurons of the inhibitory reticular thalamic nucleus (nRT) receive excitatory inputs from corticothalamic and thalamocortical axons and are thus denervated by such injuries, yet nRT cells generally survive these insults to a greater degree than TCR cells. nRT cells inhibit TCR cells, regulate thalamocortical transmission, and generate cerebral rhythms including those involved in thalamocortical epilepsies.