DUAL (EXCITATORY AND INHIBITORY) CALRETININ INNERVATION OF AMPA RECEPTOR-CONTAINING NEURONS IN THE RAT LATERAL SEPTUM

A recent study demonstrated both an extrinsic and an intrinsic calreti nin (CR) innervation of the rat septal complex and that a population o f the extrinsic calretinin fibers is aspartate/glutamate-containing. T he aim of this study was to determine which types (GluR1, GluR2/3, or both) of AMPA receptor-containing lateral septal area neurons are inne rvated by extrinsic and intrinsic CR neurons and whether the intrinsic CR cells are GABAergic. Light-and electron-microscopic single immunos taining for CR, GluR1, and GluR2/3, as well as light-and electron-micr oscopic-double immunostaining experiments for CR plus GluR1 and CR plu s GluR2/3 were performed in the lateral septal area. Furthermore, the ''mirror'' colocalization technique was employed on consecutive vibrat ome sections of the septal complex to investigate whether the intrinsi c septal CR neurons are GABAergic. The results are summarized as follo ws: (1) both GluR1- and GluR2/3-immunoreactive neurons are innervated by CR-containing fibers; (2) the majority of these synapses, observed mainly on the soma and, to a lesser extent, on proximal dendrites of A MPA receptor-containing neurons, represent asymmetric synaptic membran e specializations; (3) a minority of CR-containing axon terminals asso ciated with both GluR1- and GluR2/3-immunoreactive neurons form symmet ric contacts, predominantly on their soma; and (4) 93% of the lateral septal area CR cells are GABAergic. These observations indicate that b oth GluR1- and GluR2/3-containing lateral septal area neurons receive a dual intrinsic and extrinsic CR innervation. The former (intrinsic) CR boutons are GABAergic, while the latter form asymmetric synaptic co ntacts, are excitatory, and probably originate in the supramammillary area, since previous work has demonstrated that a population of supram ammillo-septal fibers contain aspartate and!or glutamate.