Stress-induced dynamic routing of hippocampal connectivity: a hypothesis

Recent observations have caused a drastic shift in the conception of the hippocampus as a homogeneous structure that subserves cognitive functions, either spatial maps or short term episodic memory, to a structure that is associated with both cognitive and emotional functions. In fact, the assignment of cognitive functions to the hippocampus is restricted to its dorsal sector. In contrast, the ventral hippocampus (VH) appears to be associated with control of behavioral inhibition, stress and emotional memory, but not with strictly cognitive functions. Curiously, the VH but not the dorsal hippocampus (DH) is associated with the development of affective disorders. In line with these collective observations, we and others have found that the ability to evoke a sustained long term potentiation (LTP), a cellular correlate of learning and memory, is much lower in the VH compared to the DH. Strikingly, acute stress as well as direct exposure to corticosterone affect DH and VH in an opposite manner; causing facilitation of LTP in the VH and its suppression in the DH. This double dissociative action results from activation of different steroid receptor species in the DH and VH. Since the DH and VH differ in efferent connectivity, and since the strength of LTP can be considered as an indicator of strength of synaptic connectivity, these results suggest that stress regulates the routes by which the hippocampus is functionally linked to the rest of the brain such that under stress, the ventral route to the amygdala is enabled while the dorsal route to the neocortex is suppressed. This selective routing may underlie the complex outcome of stress on hippocampal and amygdala physiology and behavior.