Septal GABAergic and hippocampal cholinergic systems interact in the modulation of anxiety

According to Gray [(1982) The neuropsychology of anxiety: an enquiry into the function of the septo-hippocampal system. Oxford: Oxford University Press; (1991) Neural systems, emotion and personality. In: Neurobiology of learning, emotion, and affect (Madden J, ed), pp 273-306. New York: Raven Press; Gray JA, McNaughton N (2000) The neuropsychology of anxiety. Oxford: Oxford University Press], the septum and the hippocampus act in concert to control anxiety. In the present study we examined a possible interaction between septal GABAergic and hippocampal cholinergic systems in the shock-probe burying test, an animal model of anxiety. In experiment 1, we found that a 10-ng infusion of muscimol in the medial septum produced a significant suppression of burying behavior, whereas lower doses (2.5 and 5.0 ng) did not. In experiment 2, we found a significant suppression of burying behavior after a 20-microg infusion of physostigmine into the dorsal hippocampus, but not after lower-dose infusions (5 and 10 microg). In experiment 3, we infused combined sub-effective doses of physostigmine and muscimol in the hippocampus and medial septum respectively. The combination of sub-effective doses of physostigmine (5 microg) and muscimol (2.5 ng) significantly reduced burying of the shock probe. The results indicate that the hippocampal cholinergic and septal GABAergic systems act synergistically in the modulation of anxiety.