Electrophysiological and Biochemical Studies of AMPA Receptor Phosphorylation and Synaptic Plasticity in Hippocampal CA1 Mini-Slices

In the hippocampus, synapses undergo activity-dependent changes in synaptic strength, and this is thought to underlie some forms of learning and memory. Different patterns of activity can selectively enhance synaptic transmission, inducing long-term potentiation (LTP), or weaken synapses, resulting in long-term depression (LTD). It is thought that the activation of specific signaling pathways will dictate the direction of plasticity, with kinases leading to LTP and phosphatases leading to LTD. These signaling molecules influence synaptic strength by modifying the phosphorylation state of many target proteins. In particular, bi-directional alterations in the phosphorylation of AMPA receptors can affect the trafficking and conductance of these receptors, which greatly impact the magnitude of synaptic strength. In order to further understand the signaling at AMPA receptors, and their contribution to synaptic plasticity, investigators employ a wide variety of approaches, from genetics and molecular biology to behavior. Here we describe our approaches using electrophysiological and biochemical methods with acute mouse hippocampal CA1 mini-slices to study GluA1 phosphorylation during LTP and LTD.