Hippocampal and prefrontal cortical inputs monosynaptically converge with individual projection neurons of the nucleus accumbens.

Afferents to the nucleus accumbens from different sources innervate specific areas of the central "core" and peripheral "shell" and are related to each other, at the light microscopical level, in an intricate overlapping and nonoverlapping way. This lack of homogeneity suggests that this region consists of circuits involving emsembles of neurons modulated by specific sets of convergent afferent inputs and abnormal regulation of such ensembles has been implicated in mental disorders. Early extracellular studies suggested that individual Acb neurons might respond to activation of afferents from more than one excitatory input: More recent studies of hippocampal and amygdalar or prefrontal cortical afferents suggest that hippocampal afferents gate the input from the prefrontal cortex or amygdala. Electrophysiological evidence for convergence of excitatory afferents in the Acb is strong and suggests that these pathways are monosynaptic. Nevertheless, this convergence has proved difficult to demonstrate anatomically as a result of the spatial distribution of the afferent inputs on the dendritic tree of the target neurons. To establish whether individual accumbens neurons receive monosynaptic input from pairs of afferents, one projection was labelled anterogradely with Phaseolus vulgaris leucoagglutinin and the second with biotinylated dextran amine (BDA) with Vector slate grey and 3,3'-diaminobenzidine tetrahydrochloride as the chromagens. Accumbens neurons possibly postsynaptic to these afferents, labelled by an in vivo focal injection of BDA, were examined using correlated light and electron microscopy to establish the proximal-distal distribution of labelled afferent synaptic inputs on their dendritic arbours. Individual cells were shown to receive monosynaptic afferent input from both ventral subiculum and prefrontal cortex, providing an anatomical framework for the hippocampal gating of other limbic inputs to the accumbens. Copyright 2002 Wiley-Liss, Inc.