The long-term goal of this project is to reveal how neuronal activity produces a lasting change in synaptic transmission and subsequently alters the electrical signaling in a neuronal network. One fundamental feature of the central nervous system is that neuronal activity can modify the characteristics of the postsynaptic response. This use-dependent change in synaptic strength may alter information processing in a neuronal circuit and information storage within the brain.
One of the proposed mechanisms for synaptic plasticity is that AMPA-type glutamate receptors present in the postsynaptic membrane undergo dynamic changes in response to alterations in synaptic activity. Alterations in the number of AMPA receptors and in their phosphorylation state can change the amplitude of the synaptic current and thereby alter the postsynaptic response. Recent work by Dr. Liu and her colleague has shown that the repetitive synaptic activation of a subset of AMPA receptors that are permeable to Ca2+ results in the rapid appearance of Ca2+-impermeable synaptic AMPA receptors in a cerebellar interneuron, the stellate cell. This switch not only reduces the amplitude of the synaptic current, but also prolongs the decay time course of the synaptic current. Interestingly, the reversal of this process, changing from Ca2+-impermeable to Ca2+-permeable AMPA receptors, occurs after epileptic seizures. This change may be involved in the pathogenesis of ischemia-induced neuronal death.
With National Science Foundation support, Dr. Liu will study the physiological consequences of the activity-dependent switch in AMPA receptor subtypes. This investigation could further our understanding of how synaptic plasticity may alter input-output relationships within a cerebellar neuronal network that is essential for several forms of well characterized motor learning. This study may also increase our understanding of cellular mechanisms underlying neurological disorders associated with excessive activation of Ca2+-permeable AMPA receptors.
