Organization of connections between the amygdala, medial prefrontal cortex, and lateral hypothalamus: a single and double retrograde tracing study in rats

Abstract

The amygdala and medial prefrontal cortex (mPFC) are highly interconnected telencephalic areas critical for cognitive processes, including associative learning and decision making. Both structures strongly innervate the lateral hypothalamus (LHA), an important component of the networks underlying the control of feeding and other motivated behaviors. The amygdala–prefrontal–lateral hypothalamic system is therefore well positioned to exert cognitive control over behavior. However, the organization of this system is not well defined, particularly the topography of specific circuitries between distinct cell groups within these complex, heterogeneous regions. This study used two retrograde tracers to map the connections from the amygdala (central and basolateral area nuclei) and mPFC to the LHA in detail, and to determine whether amygdalar pathways to the mPFC and to LHA originate from the same or different neurons. One tracer was placed into a distinct mPFC area (dorsal anterior cingulate, prelimbic, infralimbic, or rostromedial orbital), and the other into dorsal or ventral LHA. We report that the central nucleus and basolateral area of the amygdala send projections to distinct LHA regions, dorsal and ventral, respectively. The basolateral area, but not central nucleus, also sends substantial projections to the mPFC, topographically organized rostrocaudal to dorsoventral. The entire mPFC, in turn, projects to the LHA, providing a separate route for potential amygdalar influence following mPFC processing. Nearly all amygdalar projections to the mPFC and to the LHA originated from different neurons suggesting amygdala and amygdala–mPFC processing influence the LHA independently, and the balance of these parallel pathways ultimately controls motivated behaviors.

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Abbreviations

ACAd:

Anterior cingulate area, dorsal part

ACAv:

Anterior cingulate area, ventral part

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

fx:

Fornix

ILA:

Infralimbic area

LA:

Lateral amygdalar nucleus

LHA:

Lateral hypothalamic area

LHAd:

Lateral hypothalamic area, dorsal region

LHAjd:

Lateral hypothalamic area, juxtadorsomedial region

LHAjvd:

Lateral hypothalamic area, juxtaventromedial region, dorsal zone

LHAjvv:

Lateral hypothalamic area, juxtaventromedial region, ventral zone

LHAs:

Lateral hypothalamic area, suprafornical region

mPFC:

Medial prefrontal cortex

ORB:

Orbital area

ORBl:

Orbital area, lateral part

ORBm:

Orbital area, medial part

ORBv:

Orbital area, ventral part

ORBvl:

Orbital area, ventrolateral part

PL:

Prelimbic area

TU:

Tuberal nucleus

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Acknowledgments

We thank Meghana Kuthyar and Heather Mayer for technical assistance. This research was supported in part by National Institute of Health grant DK085721 to G.D.P.

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Correspondence to Gorica D. Petrovich.

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The authors declare that they have no conflict of interest.

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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. Organization of connections between the amygdala, medial prefrontal cortex, and lateral hypothalamus: a single and double retrograde tracing study in rats. Brain Struct Funct 221, 2937–2962 (2016). https://doi.org/10.1007/s00429-015-1081-0

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Keywords

  • Amygdala
  • Prefrontal cortex
  • Hypothalamus
  • Behavior
  • Motivation
  • Feeding