Commissurally projecting inhibitory interneurons of the rat hippocampal dentate gyrus: A colocalization study of neuronal markers and the retrograde tracer Fluoro-Gold

Improved methods for detecting neuronal markers and the retrograde tracer F luoro-Gold (FQ) were used,to identify commissurally projecting neurons of t he rat hippocampus. In addition to the dentate hilar mossy cells and CA3 py ramidal cells shown previously to transport retrograde tracers after inject ion into the dorsal hippocampus, FG positive interneurons of the, dentate g ranule cell layer and hilus were detected in numbers greater than previousl y reported. FG labeling of interneurons was variable among animals, but was as high as 96% of hilar somatostatin-positive interneurons, 84% of parvalb umin-positive cells of the granule cell layer and hilus combined, and 33% o f hilar calretinin-positive cells. By comparison, interneurons of the denta te molecular layer and all hippocampal subregions were conspicuously FG-neg ative. Whereas hilar mossy cells and CA3 pyramidal cells were FG-labeled th roughout the longitudinal axis, FG-positive interneurons exhibited a relati vely homotopic distribution. "Control" injections of FG into the neocortex, septum, and ventral hippocampus demonstrated that the homotopic. labeling of dentate interneurons was injection site-specific, and that the CA1-CA3 i nterneurons unlabeled by contralateral hippocampal FG injection were noneth eless able to transport FGfrom the septum. These data suggest a hippocampal organizing principle according to which virtually all commissurally projec ting hippocampal neurons share the property of being monosynaptic. targets of dentate granule cells. Because granule cells innervate their exclusively ipsilateral target cells in a highly lamellar pattern, these results sugge st that focal granule cell excitation may result in commissural inhibition of the corresponding "twin" granule cell lamella, thereby lateralizing and amplifying, the influence of the initiating discharge. (C) 2001Wiley-Liss, Inc