The hippocampal learning-behavior translation and the functional significance of hippocampal dysfunction in schizophrenia

How is hippocampal learning, including place learning, translated into behavior? The hippocampus integrates, along its septotemporal axis, substrates of rapid place learning, including entorhinal–hippocampal connectivity, with functional connectivity to subcortical sites and prefrontal cortex, which play central roles in behavioral-control functions, including sensorimotor, emotional, motivational, attentional, and executive functions. I present recent evidence that such integration, for which the intermediate hippocampus is a key neuroanatomical substrate, enables translation of rapid place learning into adaptive behavior. What are the clinical implications of the hippocampal learning-behavior translation? Focusing on hippocampal overactivity, which has emerged as a central feature of schizophrenia pathophysiology, I highlight how, due to functional connectivity enabling the learning-behavior translation, hippocampal dysfunction may cause not only memory deficits, but also neural-network disruptions underlying psychosis and attentional and executive deficits.

Research highlights► Hippocampus integrates memory mechanisms with links to behavioral-control function. ► Such integration enables hippocampal learning-behavior translation. ► Key role of intermediate hippocampus. ► Hippocampal links to behavioral control may have important clinical implications.