DISTINCT MOLECULAR AND MORPHOLOGICAL SUBCIRCUITS OF THE SUBPLATE NEURONS
Kanold, Patrick o
Looger, Loren L
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Subplate neurons (SPNs) are a population of neurons in the mammalian cerebral cortex that exist predominantly in the prenatal and early postnatal period. Loss of SPNs prevents the functional maturation of the cerebral cortex. SPNs receive subcortical input from the thalamus and relay this information to the developing cortical plate and thereby can influence cortical activity in a feed-forward manner. Little is known about potential feedback projections from the cortical plate to SPN. SPNs are also a heterogeneous population in terms of molecular and morphological identity. And the functional role of the different subpopulation of SPN remains poorly defined. This is mainly due to the lack of tools- i.e. transgenic lines and reporters to target and manipulate the SPNs at different stages of development. Hence the functional significance of the molecular diversity remains unexplored. In this study, we used a combination of genetic, molecular, anatomical and physiological approaches to address these questions and also to identify and characterize transgenic `tools' to manipulate the SPN. We identified and characterized a set of reporters and transgenic lines expressing Cre recombinase or green fluorescent protein with different levels of specificity in the subplate (SP). Using these transgenic driver lines and specific antibodies, we find that defined SPNs project to the main thalamo-recipient layers - L4 and L1 - and the spatial pattern of SPN projections to layer 4 is related to the spatial pattern of thalamo-cortical projections. However different subclasses have distinct patterns of projections with respect to the thalamic afferents. While certain subclasses have been shown to project locally, we observe that certain cell types of SPN also extend long-range projections to different thalamic nuclei. Thus molecularly defined SPN cell types are differentially integrated into the thalamo-cortical and intra-cortical connectivity. We also find a laminar difference in intra-cortical connectivity of the SPN. The first class of SPNs receives inputs from only deep cortical layers, while the second class of SPNs receives inputs from deep as well as superficial layers including layer 4 and are located more superficially. These superficial cortical inputs to SPNs emerge in the second postnatal week. Taken together, we demonstrate the presence of distinct laminar and molecular circuits in the developing subplate and characterize yet another level of heterogeneity of this population.