Submitted on September 16, 2003
Accepted on February 12, 2004
Substrates for Coincidence Detection and Calcium Signaling for Induction of Synaptic Potentiation in the Neonatal Visual Cortex
Laura A. Schrader1, Stephen P. Perrett2, Lan Ye3, and Michael J. Friedlander2*
1 Division of Neuroscience, Baylor College of Medicine, Houston, TX, USA
2 Dept.of Neurobiology and Civitan International Research Center, University of Alabama at Birmingham, Birmingham, AL, USA
3 Department of Neurobiology, Duke Univeristy, Durham, NC, USA
* To whom correspondence should be addressed. E-mail: mjf{at}nrc.uab.edu.
Regulation of the efficacy of synaptic transmission by activity-dependent processes has been implicated in learning and memory as well as in developmental processes. We previously described transient potentiation of excitatory synapses onto layer 2/3 pyramidal neurons in the visual cortex that is induced by coincident presynaptic stimulation and postsynaptic depolarization. In the adult visual cortex, activation of N-methyl-D-aspartate (NMDA) glutamate receptors is necessary to induce this plasticity. These receptors act as coincidence detectors, sensing presynaptic glutamate release and postsynaptic depolarization, and cause an influx of Ca2+ that is necessary for the potentiation. In the neurons of the neonatal visual cortex, on the other hand, coincident presynaptic stimulation and postsynaptic depolarization induce stable long-term potentiation (LTP). In addition, reduced but significant LTP can be induced in many neurons in the presence of the NMDAR antagonist, APV, despite the Ca2+ requirement. Therefore, there must be an alternative postsynaptic Ca2+ source and coincidence detection mechanism linked to the LTP induction mechanism in the neonatal cortex operating in addition to NMDARs. In this study, we find that in layer 2/3 pyramidal neurons, release of Ca2+ from inositol trisphosphate (InsP3) receptor-mediated intracellular stores and influx through voltage-gated Ca2+ channels (VGCCs) provide alternative postsynaptic Ca2+ sources. We hypothesize that InsP3Rs are coincidence detectors, sensing presynaptic glutamate release through linkage with group I metabotropic glutamate receptors (mGluRs), and depolarization, through VGCCs. We also find that the downstream protein kinases, PKA and PKC have a role in potentiation in layer 2/3 pyramidal neurons of the neonatal visual cortex.
