Calcitonin gene-related peptide-containing pathways in the rat forebrain

Abstract

The present study focuses on the topographical distribution of calcitonin gene-related peptide (CGRP)-containing cell bodies and fibers and their connections and pathways in the rat forebrain. We confirm previously reported CGRP projections from the perifornical area of the hypothalamus to the lateral septum, from the posterior thalamus to the caudate putamen and cerebral cortex, and from the parabrachial nuclei to the central extended amygdala, lateral hypothalamus, and ventromedial thalamus. Despite previous descriptions of CGRP in the central nervous system, important neuroanatomical aspects of the forebrain CGRP system remained obscure, which we addressed by using brain lesion techniques combined with modern immunohistology. We first report CGRP terminal fields in the olfactory-anterior septal region and also CGRP projections from the parabrachial nuclei to the olfactory-anterior septal region, the medial prefrontal cortex, the interstitial nucleus of the anterior commissure, the nucleus of the lateral olfactory tract, the anterior amygdaloid area, the posterolateral cortical amygdaloid nucleus, and the dorsolateral part of the lateral amygdaloid nucleus. In addition, we identified a CGRP cell group in the premamillary nuclei and showed that it projects to the medial CGRP layer of the lateral septum. CGRP fibers usually join other pathways rather than forming bundles. They run along the fornix from the hypothalamus, along the supraoptic decussations or the inferior thalamic peduncle-stria terminalis pathway from the posterior thalamus, and along the superior cerebellar peduncle, thalamic fasciculus, and ansa peduncularis from the parabrachial nuclei. This description of the forebrain CGRP system will facilitate investigation of its role in higher brain functions.

Neuronal correlates of fear conditioning in the bed nucleus of the stria terminalis

“…Last, intra-BNST infusions of calcitonin gene-related peptide (CGRP) was reported to enhance startle and increase Fos expression in CeA (Sink et al 2011). However, a patch-clamp study found that CGRP potentiates GABAergic inhibition in neurons of BNST-AL (Gungor and Pare 2012), the BNST region receiving CGRP inputs from the parabrachial nucleus (Gustafson and Greengard 1990;Dobolyi et al 2005). Since most BNST neurons are GABAergic (Esclapez et al 1993;Poulin et al 2009), these results suggest the startle enhancement produced by intra-BNST infusions of CGRP is due to the inhibition of BNST-AL neurons and consequent disinhibition of CeA.…”

Spinal cord compression injury in adult rats initiates changes in dorsal horn remodeling that may correlate with development of neuropathic pain

“…This antiserum was raised in goat against synthetic rat Tyr-CGRP (23-27) ␥-globulin and is specific for the whole molecule (1-37) and 23-37 fragment. This antibody reacts with rat CGRP but does not cross-react (<0.01%) with calcitonin, somatostatin, or amylin 8 -37 (dot blot); specific reactivity is eliminated by preincubation of the antiserum with 10 M rat CGRP (manufacturer's technical information), and fluorescence immunostaining of terminals in rat forebrain is eliminated by preincubation (2 days, room temperature) with 5 M rat CGRP (Dobolyi et al, 2005). This antibody produces a similar pattern of immunoreactivity in the rodent dorsal horn as demonstrated in numerous previous publications (e.g., Alvarez et al, 2004).…”

Stimulation of FcγRI on Primary Sensory Neurons Increases Insulin-Like Growth Factor-I Production, Thereby Reducing Reperfusion-Induced Renal Injury in Mice

“…CGRP, a 37-amino acid neuropeptide, is produced by the alternative splicing of the calcitonin gene (8). It is widely distributed in the central and peripheral nervous systems (9) and has been considered to possess diverse functions (10).…”