Abstract
Proper cell-to-cell communication and circuit function in the brain depends on the establishment of neuronal connections, or synapses. Since the mammalian brain is composed of both glutamatergic and GABAergic synaptic connections, a specific excitation/inhibition (E/I) balance is required for proper nervous system function. Disruptions to this E/I balance are associated with diseases such as epilepsy, autism spectrum disorders, and schizophrenia.\r \r Previously, the Paradis lab has shown that the molecule Semaphorin4D (Sema4D) is required for GABAergic synapse formation and signals through the PlexinB1 receptor in hippocampal rat neurons (Kuzirian, Moore et al. 2013). However, the role of the PlexinB1 and PlexinB2 receptors in glutamatergic synapse formation is unknown, as well as the identity of the Semaphorin ligand(s) which signal through PlexinB2 to mediate synapse formation. First, our work shows that PlexinB2, but not PlexinB1, is required for proper GABAergic synapse formation, while neither receptor is required for glutamatergic synapse formation. Next, I specifically demonstrate that the extracellular domain of Sema4C, Sema4D, and Sema4G can bind and signal through PlexinB2 in COS-7 cells to mediate collapse. In this context, I investigate the sufficiency of Sema4C and Sema4G to promote GABAergic synapse formation in hippocampal neurons. Finally, I demonstrate that Sema4A is sufficient to promote both glutamatergic and GABAergic synapse formation. Future experiments will aim to further elucidate the role of Sema4C and Sema4G in synapse formation as well as the signaling mechanisms by which Sema4A promotes glutamatergic and GABAergic synapse formation.