Inactivation of the dorsal or ventral hippocampus with muscimol differentially affects fear and memory.

It was recently found that temporary inactivation of the dorsal hippocampus with lidocaine impaired fear memory, whereas temporary inactivation of the ventral hippocampus did not. These site-specific deficits, however, may have resulted from disruption of axonal signals arriving from structures outside of the hippocampus, or from disruption of axons that pass through the hippocampus entirely. This is problematic because the hippocampus receives extensive afferent input from both the amygdala and the septum, which also play very important roles in fear and fear memory. To mitigate this problem, rats were infused with the GABA(A) receptor agonist muscimol, into either the dorsal or the ventral hippocampus, just after an "acquisition" session in which the rats were shocked from an electrified probe. A "retention" test in the same apparatus was conducted 24h later, when the hippocampus was no longer inactivated, and the probe was no longer electrified. Dorsal hippocampal inactivation just after acquisition impaired conditioned fear behavior (probe avoidance) during the retention test, whereas ventral hippocampal inactivation after acquisition did not. However, muscimol inactivation of the ventral hippocampus during an "acquisition" session selectively impaired unconditioned fear behavior, replicating earlier findings with lidocaine, a sodium channel blocker. Because muscimol hyperpolarizes neurons through a post-synaptic, GABA(A) receptor-mediated increase of chloride conductance-whereas lidocaine produces indiscriminate disruption of all axonal signalling-its effects are more likely to be restricted to intrinsic neurons within the area of infusion. These results provide strong evidence that afferent input from brain structures located outside of the hippocampus is not responsible for the differential effects of dorsal and ventral hippocampal inactivation on fear memory. Copyright 2010 Elsevier B.V. All rights reserved.