The Cummings lab seeks to gain a mechanistic understanding of how the brain acquires and stores memories in both health and disease. We use a multidisciplinary combination of cutting-edge approaches including viral and genetic techniques in transgenic mice, activity-dependent tagging of neural ensembles (or ‘engrams’), cell and circuit-specific in vivo optogenetic manipulations, ex vivo whole-cell electrophysiological recordings in brain slices, and in vivo calcium imaging techniques in freely behaving mice including fiber photometry and miniature head-mounted microscopes (Miniscopes).
Synaptic mechanisms of memory acquisition and storage in the mouse medial prefrontal cortex
While the ability to learn about and respond appropriately to threats is essential for survival, such responses to innocuous stimuli are maladaptive and are a prominent feature of neuropsychiatric disorders such as posttraumatic stress disorder (PTSD). In both humans and rodents, the dorsal and ventral regions of the mPFC are postulated to promote and suppress cue-elicited defensive behaviors, respectively. However, the exact circuit organization and plasticity mechanisms supporting these roles remain unclear. Our research seeks to reveal the organization, connectivity, and plasticity of circuits responsible for encoding and suppressing fear, and how these circuits might go awry in neuropsychiatric disorders like PTSD.
Mechanistic investigation of GABAergic engrams
Substantial effort has been invested in discerning the mechanisms governing memory storage in excitatory projection neurons. However, how interneurons participate in learning and memory processes remains largely unclear. We are therefore investigating how aversive and appetitive experiences can be encoded by distinct interneuron populations. Findings from this work will reveal the activity, connectivity, and plasticity of specific GABAergic engram populations and how they participate in memory acquisition, retrieval, and extinction.
Revealing the enigmatic role of glycinergic NMDA receptors in physiology and pathology
Classical N-methyl-D-aspartate (NMDA) receptors are heterotetramers composed of two glycine-binding GluN1 and two glutamate-binding GluN2 subunits. A third subunit type, the glycine-binding GluN3, can also be incorporated into receptors along with GluN1 and GluN2 subunits to form triheteromeric receptors. Intriguingly, GluN3 subunits can also assemble with two GluN1 subunits to form excitatory glycinergic receptors. The cell type- and region-specific roles of these so-called glycinergic NMDA receptors remains largely unresolved. Our lab uses innovative combinations of approaches including brain slice physiology and in vivo genetic and pharmacological manipulations to investigate how these receptors contribute to cellular and circuit plasticity and ultimately, to behavioral outcomes.