title: Postsynaptic TrkB-mediated signaling modulates excitatory and inhibitory neurotransmitter receptor clustering at hippocampal synapses.
abstract: Tyrosine receptor kinase B (TrkB)-mediated signaling modulates synaptic structure and strength in hippocampal and other neurons, but the underlying mechanisms are poorly understood. Full-length and truncated TrkB are diffusely distributed throughout the dendrites and soma of rat hippocampal neurons grown in vitro. Manipulation of TrkB-mediated signaling resulted in dramatic changes in the number and synaptic localization of postsynaptic NMDA receptor (NMDAR) and GABA(A) receptor (GABA(A)R) clusters. BDNF treatment resulted in an increase in the number of NMDAR and GABA(A)R clusters and increased the proportion of clusters apposed to presynaptic terminals. Downregulation of TrkB signaling resulted in a decrease in receptor cluster number and synaptic localization. Examination of the time course of the effects of BDNF on receptor clusters showed that the increase in GABA(A)R clusters preceded the increase in NMDAR clusters by at least 12 hr. Moreover, the TrkB-mediated effects on NMDAR clusters were dependent on GABA(A)R activation. Although TTX, APV, and CNQX treatment had no effect, blockade of GABA(A)Rs with bicuculline abolished the BDNF-mediated increase in NMDAR cluster number and synaptic localization. In contrast, application of exogenous GABA prevented the decrease in NMDAR clusters induced by BDNF scavenging. Together, these results suggest that TrkB-mediated signaling modulates the clustering of postsynaptic GABA(A)Rs and that receptor activity is required for a subsequent upregulation of NMDAR clusters. Therefore, TrkB-mediated effects on postsynaptic neurotransmitter clusters may be part of a mechanism that balances inhibitory and excitatory synaptic transmission in developing neural circuits.
authors.affiliation: Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6074, USA.
authors.forename: Sarina B
authors.initials: SB
authors.lastname: Elmariah
authors.forename: Mark A
authors.initials: MA
authors.lastname: Crumling
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Parsons
authors.forename: Rita J
authors.initials: RJ
authors.lastname: Balice-Gordon
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D011940:Receptor Aggregation / Q000502:physiology; D020813:Receptor, trkB / Q000378:metabolism*; D018091:Receptors, AMPA / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D020813:Receptor, trkB