Serotoninergic afferents preferentially innervate distinct subclasses of peptidergic interneurons in the rat visual cortex

Although it is well documented that the non-pyramidal neurons of the cerebr al cortex are under the influence of the vast serotoninegic input, the ultr astructural substrate for such functional interactions appears largely obsc ure. We sought to address this issue by dual immunoelectron microscopy, com bining antibodies against serotonin (5-HT) and three neurochemical markers for peptidergic interneurons. namely somatostatin (SRIF), neuropeptide Y (N PY) and vasoactive intestinal polypeptide (VIP). The gold-substituted silve r-peroxidase method was employed to intensify and differentiate the end-pro duct of the peptide-immunoreaction from the non-intensified 5-HT fibers. Ma inly the SRIF but also the NPY neurons were encountered among the postsynap tic targets of the 5-HT boutons. Recipients of synapses were perikarya and proximal dendrites of SRIF and NPY cells but also distal dendrites of the S RIF neurons. Neither synaptic relationships nor close appositions were ever identified between 5-HT boutons and VIP-immunoreactive elements. This rema rkable synaptic preference/avoidance of 5-HT afferents for specific peptide rgic subpopulations reveals a 'wired' component of cortical serotonin neuro transmission, which should be carefully interpreted within the frame of the available literature for extrasynaptic serotonin release. (C) 2001 Elsevie r Science B.V. All rights reserved.