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Neural substrates of fear-induced hypophagia in male and female rats

Abstract

Cessation of eating under fear is an adaptive response that aids survival by prioritizing the expression of defensive behaviors over feeding behavior. However, this response can become maladaptive when persistent. Thus, accurate mediation of the competition between fear and feeding is important in health and disease; yet, the underlying neural substrates are largely unknown. The current study identified brain regions that were recruited when a fear cue inhibited feeding in male and female rats. We used a previously established behavioral paradigm to elicit hypophagia with a conditioned cue for footshocks, and Fos imaging to map activation patterns during this behavior. We found that distinct patterns of recruitment were associated with feeding and fear expression, and that these patterns were similar in males and females except within the medial prefrontal cortex (mPFC). In both sexes, food consumption was associated with activation of cell groups in the central amygdalar nucleus, hypothalamus, and dorsal vagal complex, and exposure to food cues was associated with activation of the anterior basolateral amygdalar nucleus. In contrast, fear expression was associated with activation of the lateral and posterior basomedial amygdalar nuclei. Interestingly, selective recruitment of the mPFC in females, but not in males, was associated with both feeding and freezing behavior, suggesting sex differences in the neuronal processing underlying the competition between feeding and fear. This study provided the first evidence of the neural network mediating fear-induced hypophagia, and important functional activation maps for future interrogation of the underlying neural substrates.

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Abbreviations

ACAd:

Anterior cingulate area, dorsal part

ANOVA:

Analysis of variance

BLA:

Basolateral amygdalar nucleus

BLAa:

Basolateral amygdalar nucleus, anterior part

BLAp:

Basolateral amygdalar nucleus, posterior part

BMA:

Basomedial amygdalar nucleus

BMAa:

Basomedial amygdalar nucleus, anterior part

BMAp:

Basomedial amygdalar nucleus, posterior part

CEA:

Central amygdalar nucleus

CEAc:

Central amygdalar nucleus, capsular part

CEAl:

Central amygdalar nucleus, lateral part

CEAm:

Central amygdalar nucleus, medial part

CS:

Conditioned stimulus

DMX:

Dorsal motor nucleus vagus nerve

ILA:

Infralimbic area

LA:

Lateral amygdalar nucleus

LHA:

Lateral hypothalamic area

mPFC:

Medial prefrontal cortex

NTSm:

Nucleus of the solitary tract, medial part

PL:

Prelimbic area

PVH:

Paraventricular hypothalamic nucleus

PVHdp:

Paraventricular hypothalamic nucleus, dorsal parvicellular part

PVHmpd:

Paraventricular hypothalamic nucleus, medial parvicellular part, dorsal zone

PVHmpv:

Paraventricular hypothalamic nucleus, medial parvicellular part, ventral zone

PVHpml:

Paraventricular hypothalamic nucleus, posterior magnocellular part, lateral

PVHpv:

Paraventricular hypothalamic nucleus, periventricular part

PVT:

Paraventricular thalamic nucleus

SO:

Supraoptic nucleus, proper

US:

Unconditioned stimulus

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Acknowledgements

We thank Elizabeth Choi, Megan Ebner, Michael Hobin, Songhon Hwang, Meghana Kuthyar, Heather Mayer, Jordan Newmark, Daniel Powell, Grant Schum, Anna Whitham, and John Young for technical assistance. A portion of the research reported here partially fulfilled the requirements for the degree of PhD awarded to CJR by Boston College.

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Correspondence to G. D. Petrovich.

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All applicable international, national, and institutional guidelines for the care and use of animals were followed. All procedures performed in this study involving animals were in accordance with the ethical standards of the Boston College Institutional Animal Care and Use Committee.

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Reppucci, C.J., Petrovich, G.D. Neural substrates of fear-induced hypophagia in male and female rats. Brain Struct Funct 223, 2925–2947 (2018). https://doi.org/10.1007/s00429-018-1668-3

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Keywords

  • Amygdala
  • Prefrontal cortex
  • Hypothalamus
  • Fear
  • Feeding
  • Anorexia