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.

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The LIM domain is a zinc-binding amino acid motif that characterizes various proteins which function in protein-protein interactions and transcriptional regulation. Expression patterns of several LIM protein genes are compatible with roles in vertebrate CNS development, but little is known about the expression, regulation, or function of LIM proteins in the mature CNS. Lmo1, Lmo2, and Lmo3 are LIM-only genes originally identified as putative oncogenes that have been implicated in the control of cell differentiation and are active during CNS development. Using in situ hybridization for mRNA and immunohistochemical detection of reporter protein expression in transgenic mice, we found that Lmo1, Lmo2, and Lmo3 show individually unique but partially overlapping patterns of expression in several regions of the adult mouse forebrain, including hippocampus, caudate putamen, medial habenula, thalamus, amygdala, olfactory bulb, hypothalamus, and cerebral cortex. In the hippocampal formation, Lmo1, Lmo2, and Lmo3 show different combinatorial patterns of expression levels in CA pyramidal and dentate granule neurons, and Lmo1 is present in topographically restricted subpopulations of astrocytes. Kainic acid-induced limbic seizures differentially regulated Lmo1, Lmo2, and Lmo3 mRNA levels in hippocampal pyramidal and granule neurons, such that Lmo1 mRNA increased, whereas Lmo2 and Lmo3 mRNAs decreased significantly, with maximal changes at 6 hr after seizure onset and return to baseline by 24 hr. These findings show that Lmo1, Lmo2, and Lmo3 continue to be expressed in the adult mammalian CNS in a cell type-specific manner, are differentially regulated by neuronal activity, and may thus be involved in cell phenotype-specific regulatory functions.