Abstract

The medial prefrontal cortex (mPFC) is implicated in aspects of executive function, that include the modulation of attentional and memory processes involved in goal selection. Food-seeking behavior has been shown to involve activation of the mPFC, both during the execution of strategies designed to obtain food and during the consumption of food itself. As these behaviors likely require differential engagement of the prefrontal cortex, we hypothesized that the pattern of neuronal activation would also be behavior dependent. In this study we describe, for the first time, the expression of Fos in different layers and cell types of the infralimbic/dorsal peduncular and prelimbic/anterior cingulate subdivisions of mouse mPFC following both the consumption of palatable food and following exploratory activity of the animal directed at obtaining food reward. While both manipulations led to increases of Fos expression in principal excitatory neurons relative to control, food-directed exploratory activity produced a significantly greater increase in Fos expression than observed in the food intake condition. Consequently, we hypothesized that mPFC interneuron activation would also be differentially engaged by these manipulations. Interestingly, Fos expression patterns differed substantially between treatments and interneuron subtype, illustrating how the differential engagement of subsets of mPFC interneurons depends on the behavioral state. In our experiments, both vasoactive intestinal peptide- and parvalbumin-expressing neurons showed enhanced Fos expression only during the food-dependent exploratory task and not during food intake. Conversely, elevations in arcuate and paraventricular hypothalamic fos expression were only observed following food intake and not following food driven exploration. Our data suggest that select activation of these cell types may be required to support high cognitive demand states such as observed during exploration while being dispensable during the ingestion of freely available food.

Highlights

  • Through the receipt of information on taste and palatability from primary gustatory insular and secondary orbitofrontal taste cortices (Ongur and Price, 2000; Carleton et al, 2010) along with integration of information from other brain areas such as the amygdala and midline thalamus, the medial prefrontal cortex modulates food seeking behavior through excitatory projections to the striatum and in particular to the nucleus accumbens (Kelley, 2004)

  • The importance of a homologous region of the prefrontal cortex [Uylings et al, 2003; Kesner and Churchwell, 2011; including the prelimbic/anterior cingulate (PL/anterior cingulate cortex (AC)) and infralimbic/dorsal peduncular (IL/dorsal peduncular cortex (DP)) cortex] in driving food intake is highlighted by numerous studies, including those demonstrating the role of neuropeptides acting at prefrontal cortical μ-opioid receptors to modulate feeding (Mena et al, 2011; Blasio et al, 2013)

  • FEEDING- AND FOOD-DRIVEN EXPLORATORY BEHAVIOR-ASSOCIATED Fos EXPRESSION IN THE medial prefrontal cortex (mPFC) During the food intake assay, the time spent actively feeding on the HFD pellet including minor interaction with the dish bottom (13.8 ± 1.5 min; consumption 0.81 ± 0.09 g) was www.frontiersin.org similar to time spent pursuing the HFD locked inside the perforated dish in the exploratory behavior test (12.6 ± 1.0 min)

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Summary

Introduction

Through the receipt of information on taste and palatability from primary gustatory insular and secondary orbitofrontal taste cortices (Ongur and Price, 2000; Carleton et al, 2010) along with integration of information from other brain areas such as the amygdala and midline thalamus, the medial prefrontal cortex (mPFC; Uylings et al, 2003; Kesner and Churchwell, 2011) modulates food seeking behavior through excitatory projections to the striatum and in particular to the nucleus accumbens (Kelley, 2004). The importance of a homologous region of the prefrontal cortex [Uylings et al, 2003; Kesner and Churchwell, 2011; including the prelimbic/anterior cingulate (PL/AC) and infralimbic/dorsal peduncular (IL/DP) cortex] in driving food intake is highlighted by numerous studies, including those demonstrating the role of neuropeptides acting at prefrontal cortical μ-opioid receptors to modulate feeding (Mena et al, 2011; Blasio et al, 2013). Have shown the importance of the mPFC in cued feeding and in driving operant responding for palatable food (Petrovich et al, 2007a,b; Moscarello et al, 2010)

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