INVOLVEMENT OF DISTINCT PIONEER NEURONS IN THE FORMATION OF LAYER-SPECIFIC CONNECTIONS IN THE HIPPOCAMPUS

During neural development, specific recognition molecules provide the cues necessary for the formation of initial projection maps, which are reshaped later in development. In some systems, guiding cues for axon al pathfinding and target selection are provided by specific cells tha t are present only at critical times. For instance, the floor plate gu ides commissural axons in the spinal cord, and the subplate is involve d in the formation of thalamocortical connections. Here we study the d evelopment of entorhinal and commissural connections to the murine hip pocampus, which in the adult terminate in nonoverlapping layers. We sh ow that two groups of pioneer neurons, Cajal-Retzius cells and GABAerg ic neurons, form layer-specific scaffolds that overlap with distinct h ippocampal afferents at embryonic and early postnatal stages. Furtherm ore, at postnatal day 0 (P0)-P5, before the dendrites of pyramidal neu rons develop, these pioneer neurons are preferential synaptic targets for hippocampal afferents. Birthdating analysis using 5'-bromodeoxyuri dine (BrdU) pulses showed that most such early-generated neurons disap pear at late postnatal stages, most likely by cell death. Together wit h previous studies, these findings indicate that distinct pioneer neur ons are involved in the guidance and targeting of different hippocampa l afferents.