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Dorst, K. E.

Publications and source records attributed to Dorst, K. E..

3 recordsLinked to original sources
bioRxiv2026

Network and behavioral signatures of postpartum behavioral deficits improve with a neurosteroid-based treatment

Postpartum depression (PPD) impacts nearly 20% of mothers and a much larger percentage (up to 75%) suffer from postpartum blues. Despite this high incidence, we still have an incomplete understanding of the underlying neurobiology of PPD. Deficits in neurosteroid signaling has been implicated in the vulnerability to postpartum behavioral deficits and mice with reduced expression of {delta} subunit-containing GABAA receptors (GABAARs) (Gabrd -/- or Gabrd +/-), the predominant site of action for 5-reduced neurosteroids, exhibit behavioral deficits restricted to the postpartum period. Allopregnanolone and allopregnanolone analogs (SGE-516) can improve postpartum behavioral outcomes and their ability to modulate oscillations in the basolateral amygdala (BLA) involved in emotional processing has been proposed to contribute to their antidepressant effects. Here we demonstrate that the behavioral differences in postpartum wild type, Gabrd+/-, and SGE-516-treated Gabrd+/- dams is largely driven by theta oscillations in the BLA. Previous studies have linked theta oscillations in the BLA to altered behavioral responding in response to stress or threat. Interestingly, here we demonstrate that Gabrd+/- dams exhibit a failure to properly respond to their own pup calls, with reduced theta oscillations that correlates with deficits in maternal approach behavior both of which are restored with SGE-516 treatment. Further, unbiased MoSeq analysis identified altered behavioral syllable expression in Gabrd+/- dams in response to their pup calls compared to wild type dams that are restored with SGE-516 treatment. These findings demonstrate network and behavioral signatures of postpartum behavioral deficits and characterize the effects associated with neurosteroid-based treatment response.

neuroscience↗
bioRxiv2023

Hippocampal engrams generate flexible behavioral responses and brain-wide network states

Memory engrams are both necessary and sufficient to mediate behavioral outputs. Defensive behaviors such as freezing and avoidance are commonly examined during hippocampal-mediated fear engram reactivation, yet how reactivation of these cellular populations across different contexts engages the brain to produce a variety of defensive behaviors is relatively unclear. To address this, we first optogenetically reactivated a tagged fear engram in the dentate gyrus (DG) subregion of the hippocampus across three distinct contexts. We found that there were differential amounts of light-induced freezing depending on the size of the context in which reactivation occurred: mice demonstrated robust light-induced freezing in the most spatially restricted of the three contexts but not in the largest. We then utilized graph theoretical analyses to identify brain-wide alterations in cFos co-activation during engram reactivation across the smallest and largest contexts. Our manipulations conferred greater positive cFos correlations and recruited regions spanning putative fear and defense systems as hubs in the respective networks. Moreover, reactivating DG-mediated engrams generated network topologies across experimental conditions, emphasizing both shared and distinct features. By identifying and manipulating the circuits supporting memory function, as well as their corresponding brain-wide activity patterns, it is thereby possible to resolve systems-level biological mechanisms mediating memorys capacity to modulate behavioral states. SIGNIFICANCE STATEMENTImplementing appropriate defensive behaviors across disparate environments is essential for survival. Memories can be used to select these responses. Recent work identified and artificially manipulated cellular ensembles within the hippocampus that mediate fear memory recall, yet how these populations engage brain-wide pathways that mediate defensive behaviors under environmental contingencies is unclear. We demonstrated here that reactivation across environments of various sizes elicits different behavioral responses and corresponding brain-wide network dynamics. These findings establish the flexibility of memory-bearing ensembles in generating brain and behavior states.

neuroscience↗
bioRxiv2018

Dbx1 pre-Bötzinger complex interneurons comprise the core inspiratory oscillator for breathing in adult mice

The brainstem pre-Botzinger complex (preBotC) generates inspiratory breathing rhythms, but which neurons comprise its rhythmogenic core? Dbx1-derived neurons may play the preeminent role in rhythm generation, an idea well founded at perinatal stages of development but not in adulthood. We expressed archaerhodopsin or channelrhodopsin in Dbx1 preBotC neurons in intact adult mice to interrogate their function. Prolonged photoinhibition slowed down or stopped breathing, whereas prolonged photostimulation sped up breathing. Brief inspiratory-phase photoinhibition evoked the next breath earlier than expected, whereas brief expiratory-phase photoinhibition delayed the subsequent breath. Conversely, brief inspiratory-phase photostimulation increased inspiratory duration and delayed the subsequent breath, whereas brief expiratory-phase photostimulation evoked the next breath earlier than expected. Because they govern the frequency and precise timing of breaths in awake adult mice with sensorimotor feedback intact, Dbx1 preBotC neurons constitute an essential core component of the inspiratory oscillator, knowledge directly relevant to human health and physiology.

neuroscience↗