Biology subjects

Cummings, K. A.

Publications and source records attributed to Cummings, K. A..

3 recordsLinked to original sources

bioRxiv2023

The mouse dorsal peduncular cortex encodes fear memory

The rodent medial prefrontal cortex (mPFC) is a locus for both the promotion and suppression (e.g. extinction) of fear and is composed of four anatomically distinct subregions, including anterior cingulate 1 (Cg1), prelimbic (PL), infralimbic (IL), and the dorsal peduncular (DP) cortex. A vast majority of studies have focused on Cg1, PL, and IL. The Cg1 and PL have been implicated in the promotion of fear, while the IL has been linked to a role in the suppression, or extinction, of fear. Due to its anatomical location ventral to IL, the DP has been hypothesized to function as a fear-suppressing brain region however, no studies have explicitly tested its role in this function or in the regulation of memory generally. Moreover, some studies have pointed towards a dichotomous role for ventral mPFC in the dual suppression and promotion of fear, but the mechanisms underlying these opposing observations remains unclear. Here, we provide evidence that the DP paradoxically functions as a cued fear-encoding brain region and plays little to no role in fear memory extinction. By using a combination of cFos immunohistochemistry, whole-cell brain slice electrophysiology, fiber photometry, and activity-dependent neural tagging, we demonstrate that DP neurons exhibit learning-related plasticity, acquire cue-associated activity across learning and memory retrieval, and that DP neurons activated by learning are preferentially reactivated upon fear memory retrieval. Further, optogenetic activation and silencing of fear learning-related DP neural ensembles drives the promotion and suppression of freezing, respectively. Overall, these data suggest that the DP plays an unexpected role in fear memory encoding. More broadly, our results reveal new principles of organization across the dorsoventral axis of the mPFC.

neuroscience↗

bioRxiv2021

Ensemble encoding of conditioned fear by prefrontal somatostatin interneurons

Neurons preferentially activated by learning have been ascribed the unique potential to encode memory. However, it remains unclear which genetically-defined cell types are recruited as part of such an ensemble, or what role discrete subpopulations play in behavior. Here we show that fear conditioning activates a heterogeneous neural ensemble in the medial prefrontal cortex (mPFC), comprised to a large degree of GABAergic interneurons immunoreactive for somatostatin (SST-INs). Using an intersectional genetic approach, we demonstrate that fear learning-activated SST-INs exhibit distinct circuit properties, are preferentially reactivated during memory retrieval, and mediate the expression of defensive freezing. We further show that a rewarding experience, morphine treatment, activates an orthogonal SST-IN population that exerts opposing control over fear. These results outline an important role for discrete GABAergic ensembles in fear memory encoding, and point to an unappreciated capacity for functional specialization among SST-INs.

neuroscience↗

bioRxiv2019

Prefrontal somatostatin interneurons encode fear memory

Theories stipulate that memories are encoded within networks of cortical projection neurons (PNs). Conversely, GABAergic interneurons (INs) are thought to function primarily to inhibit PNs and thereby impose network gain control, an important but purely modulatory role. However, we found that associative fear learning potentiates synaptic transmission and cue-specific activity of medial prefrontal cortex (mPFC) somatostatin interneurons (SST-INs), and that activation of these cells controls both memory encoding and expression. Furthermore, the synaptic organization of SST- and parvalbumin (PV)-INs provides a potential circuit basis for SST-IN-evoked disinhibition of mPFC output neurons and recruitment of remote brain regions associated with defensive behavior. These data suggest that rather than constrain mnemonic processing, potentiation of SST-IN activity represents an important causal mechanism for conditioned fear.

neuroscience↗