Separable features of visual cortical plasticity revealed by N -methyl- d -aspartate receptor 2A signaling

doi:10.1073/pnas.0536089100

Separable features of visual cortical plasticity revealed by N-methyl-d-aspartate receptor 2A signaling

^*Neuronal Circuit Development, Institute of Physical and Chemical Research (RIKEN), Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; ^†Molecular Neurobiology and Pharmacology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; and ^‡Center for Neuroscience Research, Edinburgh University, 1 George Square, Edinburgh EH8–9JZ, United Kingdom

Edited by Shigetada Nakanishi, Kyoto University, Kyoto, Japan, and approved January 9, 2003 (received for review October 10, 2002)

Abstract

How individual receptive field properties are formed in the maturing sensory neocortex remains largely unknown. The shortening of N-methyl-d-aspartate (NMDA) receptor currents by 2A subunit (NR2A) insertion has been proposed to delimit the critical period for experience-dependent refinement of circuits in visual cortex. In mice engineered to maintain prolonged NMDA responses by targeted deletion of NR2A, the sensitivity to monocular deprivation was surprisingly weakened but restricted to the typical critical period and delayed normally by dark rearing from birth. Orientation preference instead failed to mature, occluding further effects of dark rearing. Interestingly, a full ocular dominance plasticity (but not orientation bias) was selectively restored by enhanced inhibition, reflecting an imbalanced excitation in the absence of NR2A. Many of the downstream pathways involved in NMDA signaling are coupled to the receptor through a variety of protein–protein interactions and adaptor molecules. To further investigate a mechanistic dissociation of receptive field properties in the developing visual system, mice carrying a targeted disruption of the NR2A-associated 95-kDa postsynaptic density (PSD95) scaffolding protein were analyzed. Although the development and plasticity of ocular dominance was unaffected, orientation preference again failed to mature in these mice. Taken together, our results demonstrate that the cellular basis generating individual sensory response properties is separable in the developing neocortex.

Footnotes

↵ § To whom correspondence should be addressed. E-mail: hensch{at}postman.riken.go.jp.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

OD,

ocular dominance;

NMDA,

N-methyl-d-aspartate;

NR,

NMDA receptor;

MD,

monocular deprivation;

Pn,

postnatal day n;

PSD95,

postsynaptic density 95-kDa protein;

CBI,

contralateral bias index;

DR,

dark rearing;

EPSC,

excitatory postsynaptic current;

AMPA,

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid;

KO,

knockout;

GAD65,

glutamic acid decarboxylase 65-kDa isoform;

LTP,

long-term potentiation;

E-I,

excitatory-inhibitory;

LR,

light-reared