Corticotropin-releasing factor in the dorsal raphe nucleus regulates activity of lateral septal neurons

Corticotropin-releasing factor (CRF) has substantial effects on brain serotonergic activity, especially in limbic structures related to stress and anxiety. For example, relatively low doses of CRF administered into the dorsal raphe nucleus (DRN) decrease DRN unit activity and serotonin release in the lateral septum (LS), a limbic target of the DRN. In contrast, higher doses of CRF tend to be excitatory on both endpoints. The present experiment sought to establish the functional connection between CRF effects in the DRN and the ultimate effect on activity in the LS as a terminal region. We recorded the effects of CRF (3, 10, 30 and 100 ng in 100 nl of artificial cerebrospinal fluid) administered into the DRN upon LS unit activity. In general, the lower doses of CRF (3 and 10 ng) had a facilitatory effect on LS unit activity, peaking at about 15-20 min post-injection. The higher doses had a more complex effect with an early suppression of unit responding maximizing at about 5 min followed by a facilitatory rebound, especially at the 100 ng dose, maximizing at about 20 min. Taken with previous studies demonstrating an inhibitory effect of 5-HT on neuronal activity in LS, the findings suggest that CRF regulation of the DRN is translated to changes in LS activity. This effect may underlie certain coping behaviors in response to stress.