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Abstract

Animals must quickly adapt food-seeking strategies to locate nutrient sources in dy-
namically changing environments. Learned associations between food and environ-
mental cues that predict its availability promote food-seeking behaviors. However,
when such cues cease to predict food availability, animals undergo “extinction” learn-
ing, resulting in the inhibition of food-seeking responses. Repeatedly activated sets
of neurons, or “neuronal ensembles,” in the dorsal medial prefrontal cortex (dmPFC)
are recruited following appetitive conditioning and undergo physiological adapta-
tions thought to encode cue-reward associations. However, little is known about how
the recruitment and intrinsic excitability of such dmPFC ensembles are modulated by
extinction learning. Here, we used in vivo 2-Photon imaging in male Fos-GFP mice
that express green fluorescent protein (GFP) in recently behaviorally activated neu-
rons to determine the recruitment of activated pyramidal and GABAergic interneu-
ron dmPFC ensembles during extinction. During extinction, we revealed a persistent
activation of a subset of interneurons which emerged from a wider population of in-
terneurons activated during the initial extinction session. This activation pattern was
not observed in pyramidal cells, and extinction learning did not modulate the excit-
ability properties of activated pyramidal cells. Moreover, extinction learning reduced
the likelihood of reactivation of pyramidal cells activated during the initial extinction ession. Our findings illuminate novel neuronal activation patterns in the dmPFC
underlying extinction of food-seeking, and in particular, highlight an important role
for interneuron ensembles in this inhibitory form of learning.