Presenting Author
New York Medical College
For 30 years, my laboratory has been engaged in work across the range of neuronal plasticity, including: 1) properties of long-term activity-dependent potentiation (LTP) and depression (LTD) of synaptic strength; 2) links between LTD and cascades underlying LTP; 3) changes in synaptic function associated with the development of epileptic seizures; and 4) cellular mechanisms that both trigger and prevent ischemia-induced delayed neuronal death. We were the first to show that induction of mammalian LTP requires cyclic AMP and new protein synthesis, and to demonstrate a novel form of LTD evoked when presynaptic inputs are active while postsynaptic neurons are hyperpolarized. This led to our describing a NO-mediated cyclic GMP-dependent biochemical cascade that is part of bi-directional cyclic nucleotide regulation of synaptic strength, discovering chemical methods of inducing this and other forms of LTD, and direct two-photon fluorescence imaging of presynaptic transmitter release to demonstrate that this form of LTD persistently modulates release from the rapidly-recycling pool of transmitter vesicles. We study the mechanisms by which impairments in long-term, activity-dependent synaptic plasticity contribute to progressive functional brain damage in pathologies such as Alzheimer's disease, traumatic brain injury, epilepsy, depression, and perinatal lead exposure.