Grant: Operating Grant

Communication between neurons occurs at specialized junctions known as synapses via a process known as synaptic transmission: neurotransmitter molecules are released from presynaptic neurons, bind to membrane receptors on the surface of postsynaptic neurons, and initiate various processes within the neuron. The strength of the synaptic transmission may then, theoretically, be regulated by changing either the presynaptic neurotransmitter release or the responsiveness of postsynaptic receptors. Research in our laboratory has focused on the mechanisms by which postsynaptic receptors are regulated. We have recently provided the first evidence suggesting that the numbers of receptors expressed on postsynaptic domains can be rapidly regulated, and that these rapid changes in postsynaptic receptor numbers may be a novel and efficient means by which the strength of synaptic transmission can be altered. In this application, we propose experiments to investigate how such rapid changes in the number of postsynaptic receptors, and hence synaptic transmission strength, are initiated and carried out. Interneuronal communication is fundamental for all aspects of brain function and alteration of this process underlies many brain disorders including epilepsy, stroke, and mental disorders. As such, our proposed studies can be expected to lead to better treatments for these diseases.