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 this neuron. The strength of the synaptic transmission may then, theoretically, be regulated by either altering 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 provided the first evidence suggesting that both channel gating (function) and the numbers of neurotransmitters on the postsynaptic domains can be rapidly regulated, and that these rapid changes 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 channel gating and number of postsynaptic receptors, and hence, synaptic transmission strength, are regulated. Interneuronal communication is fundamental to all aspects of brain function, and alteration of this process underlies many brain disorders, including epilepsy, stroke, and anxiety disorders. As such, our proposed studies can be expected to lead to better treatments for these diseases.