Biology subjects

Maguire, J. L.

Publications and source records attributed to Maguire, J. L..

3 recordsLinked to original sources

bioRxiv2026

Basolateral amygdala neurons await oscillatory recruitment into valence-relevant ensembles

Impaired valence processing is a core feature of psychiatric illnesses. The ability to rapidly evaluate situations and stimuli and determine whether they have positive or negative implications, termed valence processing, is a highly adaptive brain function that is essential for survival. Despite its importance, we still lack a complete understanding of the neural computations involved. The basolateral amygdala (BLA) plays a critical role in valence processing and valence ensembles have been identified by their anatomical location within the BLA, their projection targets, their genetic identity, or some combination of these factors. In parallel, distinct BLA oscillatory states have been shown to drive divergent valence states. Despite abundant evidence separately supporting these processes, we have failed to reconcile these disparate contributions to valence processing. Here, we demonstrate that subpopulations of BLA principal neurons are recruited in response to specific frequencies of optogenetically-driven oscillations. We provide evidence showing ensemble recruitment is a product of individual neuronal sensitivities to input frequencies that can be driven by interneuron-driven oscillatory states. We also demonstrate that oscillations driven by interneuron stimulations can activate projection-specific populations and reactivate behaviorally-relevant ensembles. Together, these findings reveal a novel neural computational mechanism governing valence processing involving the ability of interneuron-driven oscillatory states to selectively recruit populations of frequency-, projection-, and valence-specific BLA neurons to evoke distinct behavioral outcomes.

neuroscience↗

bioRxiv2025

Autonomic reflex plasticity associates with time-dependent SUDEP susceptibility in a murine model with hyperactive stress circuits

Sudden unexpected death in Epilepsy (SUDEP) is the leading cause of death in patients with Epilepsy. Although SUDEP results from cardiorespiratory arrest, its underlying mechanisms are poorly understood. Considering the significant association between stress-related disorders and Epilepsy, we hypothesized that stress exaggerates autonomic reflexes critical in cardiorespiratory function and that these exaggerated reflexes increase susceptibility to SUDEP. Experiments were performed using a novel mouse model of SUDEP where hyperreactivity of central corticotropin-releasing hormone (CRH) neurons (Kcc2/Crh) predisposes mice to SUDEP in the weeks following seizure induction based on the ventral intrahippocampal kainate (vIHKA) model of chronic Epilepsy. In our study, the vIHKA model was employed in both wild-type (WT) and Kcc2/Crh mice while they were monitored with EEG and ECG using in vivo telemetry and underwent terminal autonomic reflex testing at time points when mortality peaked and plateaued. A resting tachycardia developed by one week following vIHKA injection but subsided by day 30 in both WT and Kcc2/Crh mice. During spontaneous seizures, Kcc2/Crh mice had more pronounced reflex-like ictal bradycardias compared to WT controls that notably occurred prior ([~]10 sec) to seizure termination. vIHKA injection promoted time-dependent exaggeration of autonomic reflexes, with Kcc2/Crh mice exhibiting robust autonomic disturbances compared to WT controls, including a pronounced serotonin-mediated Bezold Jarisch reflex. Taken together, our findings indicate that increased autonomic disturbance burden parallels time-dependent SUDEP susceptibility in mice with hyperreactive stress circuits.

neuroscience↗

bioRxiv2021

Allopregnanolone mediates affective switching through modulation of oscillatory states in the basolateral amygdala

Brexanolone (allopregnanolone), was recently approved by the FDA for the treatment of post-partum depression, demonstrating long-lasting antidepressant effects. Despite our understanding of the mechanism of action of neurosteroids as positive allosteric modulators (PAMs) of GABAO_SCPLOWAC_SCPLOW receptors, we still do not fully understand how allopregnanolone exerts these persistent antidepressant effects. Here, we demonstrate that allopregnanolone and similar synthetic neuroactive steroid analogs, SGE-516 (tool-compound) and zuranolone (SAGE-217, investigational-compound), are capable of modulating oscillatory states across species, which we propose may contribute to long-lasting changes in behavioral states. We identified a critical role for interneurons in generating oscillations in the basolateral amygdala (BLA) and a role for delta-containing GABAO_SCPLOWAC_SCPLOWRs in mediating the ability of neurosteroids to modulate network and behavioral states. Actions of allopregnanolone in the BLA is sufficient to alter behavioral states and enhance BLA high-theta oscillations (6-12Hz) through delta-containing GABAO_SCPLOWAC_SCPLOW receptors, a mechanism distinct from other GABAO_SCPLOWAC_SCPLOW PAMs, such as benzodiazepines. Moreover, treatment with the allopregnanolone analog SGE-516 induces long-lasting protection from chronic stress-induced disruption of network states, which correlates with improved behavioral outcomes. Our findings demonstrate a novel molecular and cellular mechanism mediating the well-established anxiolytic and antidepressant effects of neuroactive steroids.

neuroscience↗