Electrophysiological actions of corticotropin-releasing factor in the central nervous system

A review of recent studies of the effects of corticotropin-releasing factor (CRF) on the electrical activity of central neurons indicates that CRF has predominantly excitatory actions in locus ceruleus, hippocampus, cortex, and some regions of hypothalamus. These brain areas are reported to contain immunoreactive CRF. Intracellular recordings in the hippocampal slice preparation demonstrate that the excitation in this preparation may arise from reduction of the afterhyperpolarizations (AHPs) following bursts of spikes. The postburst AHPs probably are produced by a Ca2+-dependent K+ conductance. Inasmuch as "Ca2+ spikes" recorded in the presence of tetrodotoxin are not diminished by CRF, this peptide appears to be acting either at the level of the Ca2+-dependent K+ conductance itself, or at the linkage between this conductance and Ca2+ influx or Ca2+ recognition sites. These excitatory effects are consistent with electroencephalographic recordings in awake animals, where intracerebroventricular CRF activates cortical and limbic areas and, at higher doses, evokes epileptiform activity in amygdala and hippocampus. However, predominantly inhibitory actions of CRF have been seen with extracellular single-unit recordings in a few central nervous system (CNS) areas such as lateral septum, thalamus, and the hypothalamic paraventricular nucleus. These findings, combined with those from immunohistochemical, biochemical, and behavioral studies, suggest 1) a possible neuromessenger role for CRF in extrahypothalamic regions and 2) a possible concerted function by CRF-containing elements in the CNS in an integrated behavioral response to stress.