Connections between the central nucleus of the amygdala and the midbrain periaqueductal gray: Topography and reciprocity
Abstract
Abstract Previous reports indicate that the midbrain periaqueductal gray and the central nucleus of the amygdala are interconnected but the organization of these projections has not been characterized. We have analyzed this reciprocal circuitry using anterograde and retrograde tracing methods and image analysis. Our findings reveal that innervation of periaqueductal gray from the central nucleus of the amygdala is extensive and discretely organized along the rostrocaudal axis of periaqueductal gray. In addition, the reciprocal projection from periaqueductal gray to the central nucleus of the amygdala is more extensive and more highly organized than previously suggested. Multiple or single discrete injections of wheatgerm agglutinin‐horseradish peroxidase into several rostrocaudal levels of periaqueductal gray retrogradely labeled a substantial population of neurons, predominantly located in the medial division of the central nucleus of the amygdala. Tracer injections into the central nucleus revealed a high degree of spatial organization in the projection from this nucleus to periaqueductal gray. Two discrete longitudinally directed columns in dorsomedial and lateral/ventrolateral periaqueductal gray are heavily targeted by central amygdalar inputs throughout the rostral one‐half to two‐thirds of periaqueductal gray. Beginning at the level of dorsal raphe and continuing caudally, inputs from the central nucleus terminate more uniformly throughout the ventral half of periaqueductal gray. In addition, a substantial population of periaqueductal gray neurons were retrogradely labeled from the central nucleus of the amygdala; these were heterogeneously distributed along the rostrocaudal axis of periaqueductal gray, and included both raphe and non‐raphe neurons. Thus, the present study demonstrates that periaqueductal gray receives heavy, highly organized projections from the central nucleus of the amygdala and in turn, has reciprocal connections with the central nucleus. Previous studies have demonstrated that longitudinally organized columns of output neurons located in dorsomedial and lateral/ventrolateral periaqueductal gray project to the ventral medulla. Thus, there may be considerable overlap between the two longitudinally organized terminal input columns from the central nucleus of the amygdala and the two longitudinal columns of descending projection neurons from periaqueductal gray to the ventral medulla. The central nucleus of the amygdala has been implicated in a variety of emotional/cognitive functions ranging from fear and orienting responses, defensive and aversive reactions, associative conditioning, cardiovascular regulation, and antinociception. Many of these same functions are strongly represented in the periaqueductal gray. It is noteworthy that the present results demonstrate that lateral periaqueductal gray, a preeminent central trigger site for behavioral and autonomic components of the defense/aversion response, is heavily targeted by inputs from the central nucleus of the amygdala at all levels of periaqueductal gray. Thus, the central nucleus of the amygdala to periaqueductal gray projection may be involved in the neural integration of behavioral, antinociceptive and autonomic responses with emotional state. In addition, the present demonstration of extensive reciprocal connections between the central nucleus of the amygdala and periaqueductal gray represents a route via which functional activity represented in periaqueductal gray may gain access to a forebrain structure long implicated m the integration of the cognitive and autonomic components of emotional behavior. Thus, the periaqueductal gray to central nucleus of the amygdala projection may provide a relatively direct linkage between critical species‐preserving behavioral reactions and a forebrain structure capable of influencing multiple nodal points in the descending autonomic system.
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Flight or fight is mediated through the lateral periaqueductal gray (LPAG), which activates the basic, stereotypical motor patterns of flight or fight-for example, attack, running, treading, burying.
“Flight or fight is mediated through the lateral periaqueductal gray (LPAG), which activates the basic, stereotypical motor patterns of flight or fight—for example, attack, running, treading, burying (see Figures 1 and 2).24,28,47,48”
From Fear and the Defense Cascade (2015) · cites this paper as [48]
Direct projections from the amygdala and limbic forebrain activate specific areas within the LPAG to produce these basic patterns, which control not only limb muscles but also laryngeal muscles resulting in snarling, growling, and howling.
“Direct projections from the amygdala and limbic forebrain activate specific areas within the LPAG to produce these basic patterns, which control not only limb muscles but also laryngeal muscles resulting in snarling, growling, and howling.24,48,49”
From Fear and the Defense Cascade (2015) · cites this paper as [48]
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- Authors
- Rizvi, T. A., Ennis, M., Behbehani, M. M., & Shipley, M. T.
- Affiliations
- University of Cincinnati (US)
- Venue
- Journal of Comparative Neurology
- Publisher
- Wiley
- Published
- 1991-01
- Volume
- 303
- Issue
- 1
- Pages
- 121-131
- ISSN
- 0021-9967 (ISSN-L)
- 1096-9861
- OpenAlex
- W2050251142
- Cited by
- 500
- References
- 4
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 14 · 2023: 11 · 2022: 11 · 2021: 5 · 2020: 21 · 2019: 16 · 2018: 19 · 2017: 13 · 2016: 20 · 2015: 14 · 2014: 21 · 2013: 18 · 2012: 18
- FWCI
- 8.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Comparative Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (NINDS 20643, 5r01ns020643-15, 5p01ns023348-03, NINDS 23348)
- National Institute of Neurological Disorders and Stroke (R01NS024698, NS 24698)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Keywords
- central amygdala, periaqueductal gray, reciprocal projections, dorsal raphe nucleus, ventral medulla, descending pain modulation, anterograde and retrograde tracing
- MeSH terms
- Acetylcholinesterase, Amygdala, Animals, Horseradish Peroxidase, Image Processing, Computer-Assisted, Injections, Male, Neural Pathways, Periaqueductal Gray, Rats, Inbred Strains, Wheat Germ Agglutinins, Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate, Rats
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