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New players tip the scales in the balance between excitatory and inhibitory synapses

DOI: 10.1186/1744-8069-1-12

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In the brain, excitatory and inhibitory synaptic transmission is mainly mediated by two neurotransmitters: glutamate which is released at excitatory glutamatergic synaptic contacts, and γ-amino butyric acid (GABA) which is released at inhibitory GABAergic synapses. Neural information processing is believed to be mediated by integration of excitatory and inhibitory synaptic inputs [1-3]. Therefore, precise controls must exist to maintain an appropriate number of one type of synaptic input relative to the other. This process is thought to be governed by homeostatic feedback mechanisms, however factors involved remain elusive [4,5]. Impressive work carried out in recent years has begun to address the roles of molecules involved in synapse formation. A theme that has emerged from these studies is that glutamatergic and GABAergic synapses consist of complex, yet distinct networks of proteins on the postsynaptic side. The major challenge in this field now is to understand how this molecular machinery is involved in synapse formation and specificity.The discovery of a protein complex that regulates postsynaptic glutamate receptor clustering and the formation of dendritic spines has revealed some of the mechanisms involved in excitatory synapse development. Two main groups of key regulators of excitatory synapse formation have been identified, namely postsynaptic scaffolding proteins and cell adhesion molecules (CAMs). In the first group, several proteins including members of the PSD-95 family, shank, and homer have been shown to promote excitatory synapse maturation (reviewed in [6]). Much work has focused on postsynaptic density protein-95 (PSD-95), one of the most abundant proteins in the PSD [6]. PSD-95 clustering at synapses occurs early in development, prior to other postsynaptic proteins [7], and discs large, a Drosophila homolog of PSD-95, is required for normal neuromuscular junction development in larva [8]. In addition, PSD-95 enhances AMPA-type glutamate recepto


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