Co-regulation of ocular dominance plasticity and NMDA receptor subunit expression in glutamic acid decarboxylase-65 knock-out mice.
Experience can shape cortical circuits, especially during critical periods for plasticity. In visual cortex, imbalance of activity from the two eyes during the critical period shifts ocular dominance (OD) towards the more active eye. Inhibitory circuits are crucial in this process: OD plasticity is absent in GAD65KO mice that show diminished inhibition. This defect can be rescued by application of benzodiazepines, which increase GABAergic signalling. However, it is unknown how such changes in inhibition might disrupt and then restore OD plasticity. Since NMDA dependent synaptic plasticity mechanisms are also known to contribute to OD plasticity, we investigated whether NMDA receptor levels and function are also altered in GAD65KO. There are reduced NR2A levels and slower NMDA currents in visual cortex of GAD65KO mice. Application of benzodiazepines, which rescues OD plasticity, also increases NR2A levels. Thus it appears as if OD plasticity can be restored by adding a critical amount of excitatory transmission through NR2A-containing NMDA receptors. Together, these observations can unify competing ideas of how OD plasticity is regulated: changes in either inhibition or excitation would engage homeostatic mechanisms that converge to regulate NMDA receptors, thereby enabling plasticity mechanisms and also ensuring circuit stability.
Kanold
Patrick O
PO
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Kim
Yoon A
YA
GrandPre
Tadzia
T
Shatz
Carla J
CJ
D000818:Animals; D015153:Blotting, Western; D003720:Densitometry; D003975:Diazepam / Q000494:pharmacology; D023882:Dominance, Ocular / Q000502:physiology*; D004594:Electrophysiology; D018757:GABA Modulators / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000235:genetics* / Q000502:physiology*; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology; D018079:Receptors, GABA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014793:Visual Cortex / Q000502:physiology
D018757:GABA Modulators; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2; D003975:Diazepam