Research in my laboratory primarily focuses on investigating the properties and molecular mechanisms of developmental synaptic plasticity at mammalian cortical glutamatergic synapses. Our primary approach is to use electrophysiological recordings from neurons in brain slices. This is combined with techniques such as viral expression of genes of interest in slices, 2 photon calcium imaging and glutamate uncaging. We are characterizing the mechanisms by which neuronal activity leads to both long-term and short-term synaptic plasticity at developing thalamocortical synapses and in the regulation of feed forward inhibition in layer 4. We are focusing on the role of these mechanisms in experience-dependent plasticity. Specifically we are using pharmacological and genetic tools to investigate the physiological roles of pre- and postsynaptic kainate receptors, and that of NMDA receptor NR2 subtypes. These studies enable us to understand how these synaptic mechanisms produce a functional layer 4 circuit.
| Chakrabarti, Lina; Best, Tyler K; Cramer, Nathan P et al. (2010) Olig1 and Olig2 triplication causes developmental brain defects in Down syndrome. Nat Neurosci 13:927-34 |
| Evers, Danielle M; Matta, Jose A; Hoe, Hyang-Sook et al. (2010) Plk2 attachment to NSF induces homeostatic removal of GluA2 during chronic overexcitation. Nat Neurosci 13:1199-207 |
| Isaac, John T R; Feldmeyer, Dirk (2009) Mechanisms of neocortical development. J Physiol 587:1871-2 |
| Isaac, John T R; Buchanan, Katherine A; Muller, Robert U et al. (2009) Hippocampal place cell firing patterns can induce long-term synaptic plasticity in vitro. J Neurosci 29:6840-50 |
| Walker, Craig S; Jensen, Stori; Ellison, Michael et al. (2009) A novel Conus snail polypeptide causes excitotoxicity by blocking desensitization of AMPA receptors. Curr Biol 19:900-8 |
| Luscher, Christian; Isaac, John T (2009) The synapse: center stage for many brain diseases. J Physiol 587:727-9 |
| Mistry, Rajen B; Isaac, John T R; Crabtree, John W (2008) Two differential frequency-dependent mechanisms regulating tonic firing of thalamic reticular neurons. Eur J Neurosci 27:2643-56 |
