Biology subjects

Mulloy, S. M.

Publications and source records attributed to Mulloy, S. M..

4 recordsLinked to original sources

bioRxiv2026

Chronic Stress Alters Dorsal Bed Nucleus of Stria Terminalis Synaptic Neurotransmission in a Dravet Syndrome Mouse Model

Stress is a commonly reported seizure precipitant and may contribute to the development of psychiatric comorbidities in epilepsy, yet how chronic stress interacts with epileptic circuits remains poorly understood. We investigated the impact of chronic restraint stress on physiological, behavioral, and synaptic outcomes in a mouse model of Dravet syndrome, specifically corticotropin-releasing factor (CRF) neurons in the bed nucleus of the stria terminalis (BNST), a stress-responsive region implicated in epilepsy patients. Chronic restraint stress produced divergent hypothalamic-pituitary-adrenal axis responses, with stressed Dravet syndrome mice exhibiting elevated corticosterone, increased mortality in females, and increased locomotion and anxiety-like behavior. Ex vivo electrophysiological recordings revealed that chronic stress increased spontaneous excitatory event frequency onto BNST CRF neurons in both genotypes and selectively increased sEPSC and sIPSC amplitude in Dravet syndrome mice. Evoked recordings demonstrated genotype-specific effects of stress on glutamatergic transmission in CRF neurons of the DS group. This suggests greater stress-dependent remodeling of spontaneous and evoked synaptic activity in DS. These findings suggest chronic stress may worsen physiological and behavioral outcomes in Dravet syndrome and promote specific maladaptive alterations in BNST CRF circuitry. More broadly, these results suggest that stress interacts with seizure vulnerability and potentially contributes to neuropsychiatric comorbidities and epilepsy.

neuroscience↗

bioRxiv2023

Subregion and sex differences in ethanol activation of cholinergic and glutamatergic cells in the mesopontine tegmentum

Ethanol engages cholinergic signaling and elicits endogenous acetylcholine release. Acetylcholine input to the midbrain originates from the mesopontine tegmentum (MPT), which is composed of the laterodorsal tegmentum (LDT) and the pedunculopontine tegmental nucleus (PPN). We investigated the effect of acute and chronic ethanol administration on cholinergic and glutamatergic neuron activation in the PPN and LDT in male and female mice. We show that ethanol selectively activates neurons of the PPN and not the LDT in male mice. Acute 4.0 g/kg and chronic 15 daily injections of 2.0 g/kg i.p. ethanol induced Fos expression in cholinergic and glutamatergic PPN neurons in male mice, whereas cholinergic and glutamatergic neurons of the LDT were unresponsive. In contrast, acute or chronic ethanol at either dose or duration had no effect on the activation of cholinergic or glutamatergic neurons in the MPT of female mice. Female mice had higher level of baseline activation in cholinergic neurons compared with males. We also found a population of co-labeled cholinergic and glutamatergic neurons in the PPN and LDT which were highly active in the saline- and ethanol-treated groups in both sexes. These findings illustrate the complex differential effects of ethanol across dose, time point, MPT subregion and sex.

pharmacology and toxicology↗

bioRxiv2023

Expression pattern of nicotinic acetylcholine receptor subunit transcripts in neurons and astrocytes in the ventral tegmental area and locus coeruleus

Acetylcholine is the endogenous agonist for the neuronal nicotinic acetylcholine receptor (nAChR) system, which is involved in attention, memory, affective behaviors, and substance use disorders. Brain nAChRs are highly diverse with 11 different subunits that can form multiple receptor subtypes, each with distinct receptor and pharmacological properties. Different neuronal cell types can also express different nAChR subtypes, resulting in highly complex cholinergic signaling. Identifying which nAChR subunit transcripts are expressed in cell types can provide an indication of which nAChR combinations are possible and which receptor subtypes may be most pharmacologically relevant to target. In addition to differences in expression across cell types, nAChRs also undergo changes in expression levels from adolescence to adulthood. In this study, we used fluorescent in situ hybridization to identify and quantify the expression of 4, 5, 6, {beta}2 and {beta}3 nAChR subunit transcripts in dopaminergic, GABAergic, glutamatergic, and noradrenergic neurons and astrocytes in the ventral tegmental area (VTA) and locus coeruleus (LC) in adult and adolescent, male and female C57BL/6J mice. There were distinct differences in the pattern of nAChR subunit transcript expression between the two brain regions. LC noradrenergic neurons had high prevalence of 6, {beta}2 and {beta}3 expression, with very low expression of 4, suggesting the 6(non-4){beta}2{beta}3 receptor as a main subtype in these neurons. VTA astrocytes from adult mice showed greater prevalence of 5, 6, {beta}2 and {beta}3 transcript compared with adolescent mice. These data highlight the complex nAChR expression patterns across brain region and cell type.

neuroscience↗

bioRxiv2019

Flavor-specific enhancement of electronic cigarette liquid consumption and preference in mice

BackgroundThe use of electronic cigarettes has increased over the past decade. To determine how the abuse liability of electronic cigarette liquids (e-liquids) differs from nicotine alone, and to determine the impact of flavor, we compared nicotine-containing fruit- and tobacco-flavored e-liquids, and their nicotine-free versions, to nicotine alone in mouse models of oral consumption, reward and aversion. MethodsAdult male C57BL/6J mice voluntarily consumed oral nicotine, equivalent nicotine concentrations of fruit- and tobacco-flavored e-liquid, and equivalent dilutions of the nicotine-free versions in 2-bottle choice tests. Conditioned place preference and place aversion were assessed with peripherally administered e-liquids or nicotine. Serum nicotine and cotinine levels were measured after subcutaneous injections of e-liquid or nicotine. ResultsMice showed higher consumption and preference for the fruit-flavored e-liquid compared with nicotine alone. This increase was not due to the flavor itself as consumption of the nicotine-free fruit-flavored e-liquid was not elevated until the highest concentration tested. The increased consumption and preference were not observed with the tobacco-flavored e-liquid. The conditioned place preference, place aversion and nicotine pharmacokinetics of the fruit-flavored e-liquid were not significantly different from nicotine alone. ConclusionsOur data suggest that fruit, but not tobacco flavor, increased the oral consumption of e-liquid compared with nicotine alone. Moreover, this enhancement was not due to increased consumption of the flavor itself, altered rewarding or aversive properties after peripheral administration, or altered pharmacokinetics. This flavor-specific enhancement suggests that some flavors may lead to higher nicotine intake and increased use of e-liquids compared with nicotine alone. HighlightsO_LIFruit flavor, but not tobacco flavor, enhances e-liquid consumption and preference C_LIO_LIThe nicotine-free flavored e-liquid is not preferred over nicotine alone C_LIO_LIConditioning rewarding and aversive effects are equal between nicotine and e-liquid C_LI

pharmacology and toxicology↗