Blank, T. (Thomas), Nijholt, Ingrid, Grammatopoulos, Dimitris, Randeva, Harpal S., Hillhouse, Edward W. and Spiess, Joachim (2003) Corticotropin-releasing factor receptors couple to multiple g-proteins to activate diverse intracellular signaling pathways in mouse hippocampus: role in neuronal excitability and associative learning. Journal of Neuroscience, Vol.23 (No.2). pp. 700-707. ISSN 0270-6474.

PDF WRAP_Randeva_corticotropin.pdf - Requires a PDF viewer. Download (430Kb)

Request Changes to record.

Abstract

Corticotropin-releasing factor (CRF) exerts a key neuroregulatory control on stress responses in various regions of the mammalian brain, including the hippocampus. Using hippocampal slices, extracts, and whole animals, we investigated the effects of human/rat CRF (h/rCRF) on hippocampal neuronal excitability and hippocampus-dependent learning in two mouse inbred strains, BALB/c and C57BL/6N. Intracellular recordings from slices revealed that application of h/rCRF increased the neuronal activity in both mouse inbred strains. Inhibition of protein kinase C (PKC) by bisindolylmaleimide I (BIS-I) prevented the h/rCRF effect only in hippocampal slices from BALB/c mice but not in slices from C57BL/6N mice. Inhibition of cAMP-dependent protein kinase (PKA) by H-89 abolished the h/rCRF effect in slices from C57BL/6N mice, with no effect in slices from BALB/c mice. Accordingly, h/rCRF elevated PKA activity in hippocampal slices from C57BL/6N mice but increased only PKC activity in the hippocampus of BALB/c mice. These differences in h/rCRF signal transduction were also observed in hippocampal membrane suspensions from both mouse strains. In BALB/c mice, hippocampal CRF receptors coupled to Gq/11 during stimulation by h/rCRF, whereas they coupled to Gs, Gq/11, and Gi in C57BL/6N mice. As expected on the basis of the slice experiments, h/rCRF improved context-dependent fear conditioning of BALB/c mice in behavioral experiments, and BIS-I prevented this effect. However, although h/rCRF increased neuronal spiking in slices from C57BL/6N mice, it did not enhance conditioned fear. These results indicate that the CRF system activates different intracellular signaling pathways in mouse hippocampus and may have distinct effects on associative learning depending on the mouse strain investigated.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry Q Science > QL Zoology
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Corticotropin releasing hormone, Classical conditioning -- Research, Hippocampus (Brain), Neural stimulation, Mice -- Physiology
Journal or Publication Title:	Journal of Neuroscience
Publisher:	Society for Neuroscience
ISSN:	0270-6474
Official Date:	15 January 2003
Dates:	Date Event 15 January 2003 Published
Volume:	Vol.23
Number:	No.2
Page Range:	pp. 700-707
Status:	Peer Reviewed
Access rights to Published version:	Open Access (Creative Commons)
Funder:	Max-Planck-Gesellschaft zur Förderung der Wissenschaften [Max Planck Society for the Advancement of Science], Wellcome Trust (London, England)

Data sourced from Thomson Reuters' Web of Knowledge

Request changes or add full text files to a record

Repository staff actions (login required)

View Item

Downloads