Dendritogenesis of neocortical pyramidal cells and interneurons: regulation by AMPA and NMDA receptors.

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All cortical neurons express ionotropic glutamate receptors. They are essential determinants of synaptic transmission and adult function, and important regulators of early postnatal differentiation. With an overexpression strategy, we demonstrated a contribution of specific biophysically distinct AMPA receptor isoforms for dendritic growth and spine formation of pyramidal neurons and multipolar interneurons. Furthermore, we showed that the AMPA receptor-induced dendritic growth requires NMDA receptors and L-type calcium channels. We are now focussing on two aims. First, we propose to analyze the effects of an enhancement of endogenous AMPA receptor function by using 1. an overexpression of transmembrane AMPA receptor regulatory proteins, TARPs, and 2. Ampakines as positive allosteric modulators. Little is known on the function about the various TARP isoforms in neocortical neurons, and they have not been analysed in the context of development and morphological differentiation. Second, we propose to characterize the role of NMDA receptor isoforms for dendritic growth, in particular of cortical interneurons. Knowledge of the role of NMDA receptors in interneurons is surprisingly limited. The project will deliver novel insights into the function of type I and type II TARPS in the two cortical neuron classes, and unravel the role of NMDA receptors, in particular for interneuronal differentiation.