Biology subjects

Bolshakov, V. Y.

Publications and source records attributed to Bolshakov, V. Y..

4 recordsLinked to original sources

bioRxiv2024

Sex-specific behavioral and thalamo-accumbal circuit adaptations after oxycodone abstinence.

Opioid use disorder is characterized by compulsive drug seeking and heightened relapse vulnerability following abstinence, a phenomenon known as incubation of craving. Although preclinical data suggest similar behavioral expression of opioid use between sexes, conclusive evidence on sex differences in craving and relapse across abstinence periods remains lacking. Here, we investigated the effects of abstinence from oxycodone self-administration on neurotransmission in the paraventricular thalamus (PVT) to nucleus accumbens shell (NAcSh) pathway in male and female rats. Using optogenetics and ex vivo electrophysiology, we assessed synaptic strength, glutamate release probability, and intrinsic excitability of NAcSh medium spiny neurons (MSNs) following 1 (acute) or 14 (prolonged) days of forced abstinence. No sex differences were observed in oxycodone self-administration or somatic withdrawal. However, females exhibited greater cue-induced relapse after prolonged but not acute abstinence. Prolonged abstinence produced comparable increases in PVT-NAcSh synaptic strength and presynaptic glutamate release probability in both sexes, while inhibitory transmission and MSN excitability were largely unaltered. The dissociation between comparable circuit-level plasticity and sex-specific relapse vulnerability suggests that PVT-NAcSh strengthening represents a shared neuroadaptation to oxycodone abstinence, while mechanisms driving heightened relapse in females likely involve additional circuit elements that remain to be identified.

neuroscience↗

bioRxiv2024

Intra-amygdala circuits of sleep disruption-induced anxiety in female mice

Combining mouse genetics, electrophysiology, and behavioral training and testing, we explored how sleep disruption may affect the function of anxiety-controlling circuits, focusing on projections from the basolateral nucleus of the amygdala (BLA) to CRF-positive cells in the lateral division of the central amygdala (CeL). We found in Crh-IRES-Cre::Ai14(tdTomato) reporter female mice that 6 hours of sleep disruption during their non-active (light) cycle may be anxiogenic. Notably, the AMPAR/NMDAR EPSC amplitude ratio at the BLA inputs to CRF-CeL cells (CRFCeL), assessed with whole-cell recordings in ex vivo experiments, was enhanced in slices from sleep-disrupted mice, whereas paired-pulse ratio (PPR) of the EPSCs induced by two closely spaced presynaptic stimuli remained unchanged. These findings indicate that sleep disruption-associated synaptic enhancements in glutamatergic projections from the BLA to CRF-CeL neurons may be postsynaptically expressed. We found also that the excitation/inhibition (E/I) ratio in the BLA to CRFCeL inputs was increased in sleep-disrupted mice, suggesting that the functional efficiency of excitation in BLA inputs to CRFCeL cells has increased following sleep disruption, thus resulting in their enhanced activation. The latter could be translated into enhanced anxiogenesis as activation of CRF cells in the CeL was shown to promote anxiety-like behaviors.

neuroscience↗

bioRxiv2023

Impact of social dominance hierarchy on PACAP expression in the extended amygdala, corticosterone, and behavior in C57BL/6 male mice

The natural alignment of animals into social dominance hierarchies produces adaptive, and potentially maladaptive, changes in the brain that influence health and behavior. Aggressive and submissive behaviors assumed by animals through dominance interactions engage stress-dependent neural and hormonal systems that have been shown to correspond with social rank. Here, we examined the impact of social dominance hierarchies established within cages of group-housed laboratory mice on expression of the stress peptide pituitary adenylate cyclase-activating polypeptide (PACAP) in areas of the extended amygdala comprising the bed nucleus of the stria terminalis (BNST) and central nucleus of the amygdala (CeA). We also quantified the impact of dominance rank on corticosterone (CORT), body weight, and behavior including rotorod and acoustic startle response. Weight-matched male C57BL/6 mice, group-housed (4/cage) starting at 3 weeks of age, were ranked as either most-dominant (Dominant), least-dominant (Submissive) or in-between rank (Intermediate) based on counts of aggressive and submissive encounters assessed at 12 weeks-old following a change in homecage conditions. We found that PACAP expression was significantly higher in the BNST, but not the CeA, of Submissive mice compared to the other two groups. CORT levels were lowest in Submissive mice and appeared to reflect a blunted response following social dominance interactions. Body weight, motor coordination, and acoustic startle were not significantly different between the groups. Together, these data reveal changes in specific neural/neuroendocrine systems that are predominant in animals of lowest social dominance rank, and implicate PACAP in brain adaptations that occur through the development of social dominance hierarchies.

neuroscience↗

bioRxiv2022

Prefrontal cortex melanocortin 4 receptors (MC4R) mediate food intake behavior in mice

BackgroundMelanocortin 4 receptor (MC4R) activity in the hypothalamus is crucial for regulation of metabolism and food intake. The peptide ligands for the MC4R are associated with feeding, energy expenditure, and also with complex behaviors that orchestrate energy intake and expenditure, but the downstream neuroanatomical and neurochemical targets associated with these behaviors are elusive. In addition to strong expression in the hypothalamus, the MC4R is highly expressed in the medial prefrontal cortex, a region involved in executive function and decision-making. MethodsUsing viral techniques in genetically modified mice combined with molecular techniques, we identify and describe the neuronal dynamics, and define the effects on feeding behavior of a novel population of MC4R expressing neurons in the infralimbic region of the cortex. ResultsHere, we describe a novel population of MC4R-expressing neurons in the infralimbic (IL) region of the mouse prefrontal cortex that are glutamatergic, receive input from melanocortinergic neurons of the arcuate hypothalamus, and project to multiple regions that coordinate appetitive responses to food-related stimuli. The neurons are depolarized by application of MC4R-specific peptidergic agonist, THIQ. Deletion of MC4R from the IL neurons causes increased food intake and body weight gain and impaired executive function in simple food-related behavior tasks. ConclusionTogether, these data suggest that MC4R neurons of the IL play a critical role in the regulation of food intake.

neuroscience↗