Hippocampal neurons containing GABA-, cholecystokinin(CCK)-, vasoactive intestinal polypeptide(VIP)-, or somatostatin(SS)-like immunoreactivity (LI) were localized in sections of rat hippocampus. GABA-, CCK-, VIP, and SS-LI are found exclusively in interneurons of the area dentata and hippocampus. In the area dentata, GABA-LI occurs in cells of all strata but predominates in type 1 and 2 basket cells. CCK-LI is present in a subset of these basket cells and some hilar cells. VIP-LI is present in a distinct subset of dentate interneurons that, unlike the type 1 and 2 basket cells, do not contribute to the fiber plexus in the inner molecular layer. These VIP-LI interneurons send their axons to nearby granule cells and form a plexus in the hilus. SS-LI, although rare in cells of the molecular and granular layers, is present in a large population of hilar interneurons that do not exhibit GABA-, CCK-, or VIP-LI. In area CA3 of the hippocampus, a variety of morphologically diverse interneurons containing GABA-, CCK-, VIP-, or SS-LI are present in all strata. In area CA1, SS-LI is present mainly in cells of strata oriens and pyramidale. GABA- CCK- and VIP-LI interneurons are present in all strata of CA1 but, unlike the SS-LI cells, are most numerous in strata pyramidale and radiatum. These findings in the area dentata, taken together with those of Kosaka et al. (J. Comp. Neurol. 239:967-969, '85), indicate that two main populations of interneurons can be discriminated on the basis of the substances they contain. One is a group of GABA-LI cells, some of which also contain CCK- and/or VIP-LI. These cells innervate the granule cells and the second group of interneurons, the SS-LI hilar cells, which apparently form part of the dentate ipsilateral associational/commissural projections.

Phosphorylation of molecules involved in synaptic transmission by multifunctional protein kinases modulates both pre- and post-synaptic events in the central nervous system. The positioning of kinases near their substrates may be an important part of the regulatory mechanism. The A-kinase-anchoring proteins (AKAPs; ref. 3) are known to bind the regulatory subunit of cyclic AMP-dependent protein kinase A with nanomolar affinity. Here we show that anchoring of protein kinase A by AKAPs is required for the modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate channels. Intracellular perfusion of cultured hippocampal neurons with peptides derived from the conserved kinase binding region of AKAPs prevented the protein kinase A-mediated regulation of AMPA/kainate currents as well as fast excitatory synaptic currents. This effect could be overcome by adding the purified catalytic subunit of protein kinase. A control peptide lacking kinase-binding activity had no effect. To our knowledge, these results provide the first evidence that anchoring of protein kinase A is crucial in the regulation of synaptic function.

The opioid peptide dynorphin is widely distributed in neuronal tissue of rats. By immunocytochemical methods, it was shown previously that dynorphin-like immunoreactivity is present in the posterior pituitary and the cells of the hypothalamic neurosecretory magnocellular nuclei which also are responsible for the synthesis of oxytocin, vasopressin, and their neurophysins. By using an affinity-purified antiserum to the non-enkephalin part of the dynorphin molecule it has now been demonstrated that dynorphin and vasopressin occur in the same hypothalamic cells of rats, whereas dynorphin and oxytocin occur in separate cells. Homozygous Brattleboro rats (deficient in vasopressin) have magnocellular neurons that contain dynorphin separate from oxytocin. Thus dynorphin and vasopressin, although they occur in the same cells, appear to be under separate genetic control and presumably arise from different precursors.