Research in my laboratory primarily focuses on investigating the properties and molecular mechanisms of developmental synaptic plasticity in 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. The major areas of interest are summarized below:? Developmental plasticity in the barrel cortex: We are characterizing the mechanisms by which neuronal activity leads to both long-term and short-term synaptic plasticity at developing thalamocortical synapses. We are focusing on the role of these mechanisms in experience-dependent plasticity. ? The role of kainate receptors in the development of cortical circuits: Using pharmacological and genetic tools we are investigating the physiological roles of pre- and postsynaptic kainate receptors at developing synapses in the hippocampus and barrel cortex. We are particularly focusing on their involvement in developmental synaptic plasticity in these systems.? Molecular mechanisms of AMPA and kainate receptor trafficking in the activity-dependent regulation of synaptic strength: We are investigating the roles of proteins that interact with AMPA receptor and kainate receptor subunits in the functional regulation of these receptors. We use two main approaches: 1) acute blockade of specific interactions by introducing peptides into individual neurons, and 2) chronic over expression of constructs of interest using Sindbis virus in acute cultured slices. The effects of these manipulations are then assessed by investigating changes in AMPA or kainate receptor-mediated synaptic transmission and plasticity. ? Molecular determinants of kainate and NMDA receptor trafficking: We are investigating the molecular mechanisms regulating NR1/NR2C, and KA2, GluR5 and GluR6 trafficking. We are characterizing a series of mutants using electrophysiological assays of transiently transfected heterologous cells.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Intramural Research (Z01)
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Vázquez-Santiago, Fabián; García, Yashira; Rivera-Román, Ivelisse et al. (2015) Longitudinal Analysis of Cerebrospinal Fluid and Plasma HIV-1 Envelope Sequences Isolated From a Single Donor with HIV Asymptomatic Neurocognitive Impairment. J Virol Antivir Res 4:
Luscher, Christian; Isaac, John T (2009) The synapse: center stage for many brain diseases. J Physiol 587:727-9
Terashima, Akira; Pelkey, Kenneth A; Rah, Jong-Cheol et al. (2008) An essential role for PICK1 in NMDA receptor-dependent bidirectional synaptic plasticity. Neuron 57:872-82
Daw, Michael; Isaac, John (2007) Electrophysiological recordings from neonatal neocortical brain slices. Curr Protoc Neurosci Chapter 6:Unit 6.23
Daw, Michael I; Scott, Helen L; Isaac, John T R (2007) Developmental synaptic plasticity at the thalamocortical input to barrel cortex: mechanisms and roles. Mol Cell Neurosci 34:493-502
Daw, Michael I; Ashby, Michael C; Isaac, John T R (2007) Coordinated developmental recruitment of latent fast spiking interneurons in layer IV barrel cortex. Nat Neurosci 10:453-61
Scott, Helen L; Braud, Stephanie; Bannister, Neil J et al. (2007) Synaptic strength at the thalamocortical input to layer IV neonatal barrel cortex is regulated by protein kinase C. Neuropharmacology 52:185-92
Chen, Bo-Shiun; Braud, Stephanie; Badger 2nd, John D et al. (2006) Regulation of NR1/NR2C N-methyl-D-aspartate (NMDA) receptors by phosphorylation. J Biol Chem 281:16583-90
Plant, Karen; Pelkey, Kenneth A; Bortolotto, Zuner A et al. (2006) Transient incorporation of native GluR2-lacking AMPA receptors during hippocampal long-term potentiation. Nat Neurosci 9:602-4
Lauri, Sari E; Vesikansa, Aino; Segerstrale, Mikael et al. (2006) Functional maturation of CA1 synapses involves activity-dependent loss of tonic kainate receptor-mediated inhibition of glutamate release. Neuron 50:415-29

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