Elsevier

Neuroscience

Volume 126, Issue 3, 2004, Pages 533-540
Neuroscience

Hippocampal corticotropin releasing hormone: pre- and postsynaptic location and release by stress

https://doi.org/10.1016/j.neuroscience.2004.03.036Get rights and content

Abstract

Neuropeptides modulate neuronal function in hippocampus, but the organization of hippocampal sites of peptide release and actions is not fully understood. The stress-associated neuropeptide corticotropin releasing hormone (CRH) is expressed in inhibitory interneurons of rodent hippocampus, yet physiological and pharmacological data indicate that it excites pyramidal cells. Here we aimed to delineate the structural elements underlying the actions of CRH, and determine whether stress influenced hippocampal principal cells also via actions of this endogenous peptide.

In hippocampal pyramidal cell layers, CRH was located exclusively in a subset of GABAergic somata, axons and boutons, whereas the principal receptor mediating the peptide's actions, CRH receptor 1 (CRF1), resided mainly on dendritic spines of pyramidal cells. Acute ‘psychological’ stress led to activation of principal neurons that expressed CRH receptors, as measured by rapid phosphorylation of the transcription factor cyclic AMP responsive element binding protein. This neuronal activation was abolished by selectively blocking the CRF1 receptor, suggesting that stress-evoked endogenous CRH release was involved in the activation of hippocampal principal cells.

Section snippets

Animals and tissue handling

Brains of immature Sprague–Dawley-derived rats (approximately P18, when density of CRH-expressing neurons in hippocampal pyramidal cell layers is maximal; Chen et al., 2001a) and young adult mice (C57/BL6) were used. Animals were born and maintained in a quiet, uncrowded, NIH-approved facility on a 12-h light/dark cycle, and brains were harvested under relatively stress-free conditions (Yan et al., 1998). Animals were undisturbed for 24 h prior to experiments, and were then deeply anesthetized

Presumed releasable pools of hippocampal CRH are located in axon terminals of GABAergic interneurons

Consistent with earlier studies (Sakanaka et al., 1987, Yan et al., 1998, Chen et al., 2001a), CRH was expressed in basket-type interneurons within the hippocampal pyramidal cell layer (Fig. 1A). These CRH-immunoreactive somata co-expressed mRNA for the GABA synthesizing enzyme glutamic acid decarboxylase (GAD67; Fig. 1B–D). Robust CRH-immunoreactivity was apparent within the perisomatic axonal ‘baskets’ surrounding principal cells (Fig. 1A, arrows), and double-labeling confirmed that

Discussion

The principal findings of these studies are: (1) The hippocampal CRH ‘system’ is organized with CRH expressed in GABAergic interneurons and the mediating receptor on dendritic spines of principal cells, (2) stress induces molecular/ transcriptional activation of hippocampal pyramidal cells, (3) stress-induced activation of a subset of hippocampal neurons requires activation of CRH receptors expressed by these cells, and (4) blocking central CRH receptors without interfering with the peripheral

Acknowledgements

The authors thank Karin Mews and Aniko Schneider for help with the EM studies, and M. Hinojosa for excellent editorial assistance. Grant number: NS28912, NS39307 (TZB), SFB 505 (MF). Grant sponsor: NIH and Deutsche Forschungsgemeinschaft.

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