PROJECT SUMMARY
Attention is comprised of several component processes, including sustained attention, selective
attention, and attentional flexibility. The first phase, the initial focusing of attention, precludes engagement of
other components making it an important building block of many of our more complex behaviors. Additionally,
attention impairments often present as a comorbidity in conditions including but not limited to schizophrenia,
autism, depression, and epilepsy, making identifying therapeutic targets a significant public health concern.
Convergent data point to the medial prefrontal cortex (mPFC) as a hub for supporting attentional shifting along
with other key structures, while its role in the initial engagement of attention is less clear. Somehow, mPFC
pyramidal neurons integrate information from multiple sources, represent task rules, cue, and response-related
information in dynamically active ensembles, and select appropriate behavioral responses. Previous
physiological data suggests this astounding computational feat is made possible due to the powerful regulation
of pyramidal neuron activity by cortical inhibitory interneurons, but many studies lacked the ability to monitor
distinct cell-classes with specificity. Using fiber photometry of GCaMP-mediated Ca2+ signals in mPFC
parvalbumin-expressing interneurons (PVINs), we have collected preliminary data demonstrating that PVINs
play a novel role in cue-perception during a visual attentional engagement task (AET). Specifically, we have
observed that cue-evoked population increases in PVIN activity are necessary, sufficient, and can be predictive
for successful attentional engagement. We hypothesize that this may represent a universal mechanism of
attention that is consistently disrupted across diseases with attentional impairments. PVINs however, do not
operate in isolation, and mPFC pyramidal neurons are also regulated by long-range inputs from the
mediodorsal thalamus (MD) among others, and local circuit interactions with other interneuron subtypes, such
as somatostatin (SOM) and vasoactive intestinal polypeptide (VIP) expressing interneurons, all of which have
also been linked to cognition and psychiatric disease dysfunction. Separate studies have identified distinct
disinhibitory circuits involving VIP and SST interneurons, and SST and PV interneurons that can regulate
mPFC-dependent behaviors. However, the precise circuit motifs which regulate attentional processes are
largely uncharacterized. Specifically, how individual interneurons in specific classes represent information
during attentional assays capturing distinct components of attention remains to be determined. Through the
K99 phase, I will receive critical training in in vivo Ca2+ imaging and design and implementation of attentional
tasks to test my overall hypothesis that PVINs provide broad inhibition to suppress distracting information
during attentional engagement, while the R00 phase will examine how separate disinhibitory circuit motifs allow
pyramidal neuron ensembles to signal cue and response information to appropriately guide separate attention
functions.