Abstract
Central regulation of hypothalamo-pituitary-adrenocortical (HPA) axis stress responses is mediated by a relatively circumscribed group of projections to the paraventricular hypothalamus (PVN). The dorsomedial hypothalamus (DMH), medial preoptic area (mPOA), and bed nucleus of the stria terminalis (BST) provide direct, predominantly inhibitory, innervation of the PVN. These PVN-projecting neurons are controlled by descending information from limbic forebrain structures, including the prefrontal cortex, amygdala, hippocampus, and septum. The neurochemical phenotype of limbic circuits targeting PVN relays has not been systematically analyzed. The current study combined retrograde tracing and immunohistochemistry/in situ hybridization to identify the specific sites of glutamatergic and GABAergic inputs to the DMH, mPOA, and BST. Following Fluoro-gold (FG) injections in the DMH, retrogradely labeled cells co-localized with vesicular glutamate transporter mRNA in the prefrontal cortex, ventral hippocampus, and paraventricular thalamus. Co-localization of FG and glutamic acid decarboxylase mRNA was present throughout the central and medial amygdaloid nuclei and septal area. In addition, the mPOA received predominantly GABAergic input from the septum, amygdala, and BST. The BST received glutamatergic projections from the hippocampus and basomedial amygdala, whereas, GABAergic inputs arose from central and medial amygdaloid nuclei. Thus, discrete sets of neurons in the hypothalamus and BST are positioned to summate limbic inputs into PVN regulation and may play a role in HPA dysfunction and stress-related illness.
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Abbreviations
- AHN:
-
Anterior hypothalamic nucleus
- BMA:
-
Basomedial amygdala
- BST:
-
Bed nucleus of the stria terminalis
- CeA:
-
Central nucleus of the amygdala
- CoA:
-
Cortical amygdala
- CRH:
-
Corticotrophin-releasing hormone
- DMH:
-
Dorsomedial hypothalamus
- FG:
-
Fluoro-gold
- GAD65:
-
Glutamic acid decarboxylase 65
- HPA:
-
Hypothalamo-pituitary-adrenal
- LH:
-
Lateral hypothalamus
- LS:
-
Lateral septum
- MeA:
-
Medial nucleus of the amygdala
- mPFC:
-
Medial prefrontal cortex
- MPN:
-
Medial preoptic nucleus
- NAc:
-
Nucleus accumbens
- PA:
-
Posterior amygdala
- PAG:
-
Periaqueductal gray
- PH:
-
Posterior hypothalamus
- POA:
-
Preoptic area
- PVN:
-
Paraventricular nucleus of the hypothalamus
- PVT:
-
Paraventricular nucleus of the thalamus
- Reu:
-
Reuniens nucleus
- vGluT1:
-
Vesicular glutamate transporter 1
- vGluT2:
-
Vesicular glutamate transporter 2
- VMH:
-
Ventromedial hypothalamus
- vSub:
-
Ventral subiculum
- ZI:
-
Zona incerta
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Acknowledgments
This work was supported by NIH grants MH049698, MH069725, MH069860, and MH090574 to JPH. The authors wish to thank Chun Xiao and Dana Ziegler for technical assistance.
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Myers, B., Mark Dolgas, C., Kasckow, J. et al. Central stress-integrative circuits: forebrain glutamatergic and GABAergic projections to the dorsomedial hypothalamus, medial preoptic area, and bed nucleus of the stria terminalis. Brain Struct Funct 219, 1287–1303 (2014). https://doi.org/10.1007/s00429-013-0566-y
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DOI: https://doi.org/10.1007/s00429-013-0566-y