The hippocampus as a common target of neurotoxic agents

The hippocampus (HPC) is in a strategic position to process information derived from the polymodal association areas of the neocortex and to redistribute it to cortical and subcortical regions involved in the modulation of complex behavioral processes. Several converging lines of evidence indicate that the HPC and its cholinergic input are an important neurobiological substrate for learning and memory processes. Destruction of the HPC proper, its afferent projections, and its cholinergic innervation, produces a persistent impairment in cognitive function. Since alterations in learning and memory are a common consequence of toxicant exposure it is possible that the HPC is an important target site for neurotoxicity. In fact, the HPC has been shown to be preferentially susceptible to a wide variety of toxic insults and disease states. For example, the HPC is damaged by a number of environmental toxicants (heavy metals and their alkyl derivatives), metabolic perturbations, neuroactive viruses, cerebrovascular insufficiency, and neurodegenerative diseases. The susceptibility of this structure to a broad spectrum of insults and its involvement in higher order cognitive processes makes it an important focal point for studies of behavioral and neurological toxicity. Neurobiological characteristics of the HPC that might make this structure uniquely susceptible to toxic insult are discussed.