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This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 98/3/1610    most recent 00219.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Albright, M. J. Articles by Crair, M. C. Search for Related Content PubMed PubMed Citation Articles by Albright, M. J. Articles by Crair, M. C.

Increased Thalamocortical Synaptic Response and Decreased Layer IV Innervation in GAP-43 Knockout Mice

¹Departments of Neuroscience and ²Molecular and Human Genetics, ³Program in Developmental Biology, Baylor College of Medicine, Houston, Texas; and ⁴Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut

Submitted 28 February 2007; accepted in final form 18 June 2007

The growth-associated protein, GAP-43, is an axonally localized neuronal protein with high expression in the developing brain and in regenerating neurites. Mice that lack GAP-43 (GAP-43^–/–) fail to form a whisker-related barrel map. In this study, we use GAP-43^–/– mice to examine GAP-43 synaptic function in the context of thalamocortical synapse development and cortical barrel map formation. Examination of thalamocortical synaptic currents in an acute brain slice preparation and in autaptic thalamic neurons reveals that GAP-43^–/– synapses have larger -amino-3-hydroxyl-5-methyl-4-isoxazolepropionate receptor (AMPAR)-mediated currents than controls despite similar AMPAR function and normal probability of vesicular release. Interestingly, GAP-43^–/– synapses are less sensitive to blockade by a competitive glutamate receptor antagonist, suggesting higher levels of neurotransmitter in the cleft during synaptic transmission. Field excitatory postsynaptic potentials (EPSPs) from GAP-43^–/– thalamocortical synapses reveal a reduced fiber response, and anatomical analysis shows reduced thalamic innervation of barrel cortex in GAP-43^–/– mice. Despite this fact synaptic responses in the field EPSPs are similar in GAP-43^–/– mice and wild-type littermate controls, and the ratio of AMPAR-mediated to N-methyl-D-aspartate receptor (NMDAR)-mediated currents (AMPAR:NMDAR ratio) is larger than normal. This suggests that GAP-43^–/– mice form fewer thalamocortical synapses in layer IV because of decreased anatomical innervation of the cortex, but the remaining contacts are individually stronger possibly due to increased neurotransmitter concentration in the synaptic cleft. Together, these results indicate that in addition to its well known role in axonal pathfinding GAP-43 plays a functional role in regulating neurotransmitter release.