Substrates for Coincidence Detection and Calcium Signaling for Induction of Synaptic Potentiation in the Neonatal Visual Cortex

• Published in: Journal of neurophysiology 2004-06, Vol.91 (6), p.2747-2764
• Main Authors: Schrader, Laura A, Perrett, Stephen P, Ye, Lan, Friedlander, Michael J
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Calcium Signaling - drug effects; Calcium Signaling - physiology; Excitatory Amino Acid Antagonists - pharmacology; Female; Guinea Pigs; Male; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - physiology; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Visual Cortex - cytology; Visual Cortex - drug effects; Visual Cortex - physiology
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00908.2003

Department of Neurobiology and Civitan International Research Center, University of Alabama at Birmingham, Birmingham, Alabama 35294 Submitted 16 September 2003; accepted in final form 12 February 2004 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 Ca 2+ 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 NMDA receptor (NMDAR) antagonist, 2-amino-5-phosphonovaleric acid despite the Ca 2+ requirement. Therefore there must be an alternative postsynaptic Ca 2+ 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 Ca 2+ from inositol trisphosphate (InsP 3 ) receptor-mediated intracellular stores and influx through voltage-gated Ca 2+ channels (VGCCs) provide alternative postsynaptic Ca 2+ sources. We hypothesize that InsP 3 Rs 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. Address for reprint requests and other correspondence: M. J. Friedlander, CIRC 516, 1719 Sixth Ave., South, Dept. of Neurobiology, UAB, Birmingham, AL, 35294–0021 (E-mail: mjf{at}nrc.uab.edu ).