Related Experiment Videos
Disruption of experience-dependent synaptic modifications in striate cortex by infusion of an NMDA receptor
M F Bear1, A Kleinschmidt, Q A Gu
1Max Planck Institut für Hirnforschung, Frankfurt, Federal Republic of Germany.
Abstract:
To assess the possibility that NMDA receptors play a special role in visual cortical plasticity, the selective antagonist 2-amino-5-phosphonovaleric acid (APV) was continuously infused into the striate cortex of kittens as the visual environment was manipulated during the critical period. The cortex was studied using single-unit recording from sites between 3 and 6 mm from the infusion cannulae. One week of D,L-APV infusion coincident with monocular deprivation or "reverse suture" produced a concentration-dependent increase in the percentage of neurons that (1) lacked normal orientation selectivity and (2) were responsive to stimulation of the deprived eye. These effects outlasted the presence of the drug in the tissue. APV treatment also prevented the acquisition of selectivity and visual responsiveness that normally results from monocular visual experience after dark-rearing. Lasting effects of chronic APV infusion were not observed in adult striate cortex. The effects of APV on kitten striate cortex depended on the presence of the D stereoisomer as infusion of L-APV was without effect. Estimates of extracellular concentration using 3H-APV indicated that significant effects could be obtained with concentrations as low as 20 microM D,L-APV. Recordings from units during infusion indicated that visual responses were reduced by APV. Nonetheless, a normal percentage of visually responsive neurons was found at sites greater than or equal to 3 mm from the infusion cannula. There was no evidence that chronic APV infusion affected the sampling frequency of recorded neurons or disrupted cytoarchitecture at the sites further than 3 mm from the infusion cannula. Taken together, the data indicate that the effects of APV on kitten striate cortex are likely due specifically to the blockade of NMDA receptors. These data are considered in relation to several hypotheses concerning the role of NMDA receptors in the experience-dependent development of striate cortex.
Insights
NMDA receptor blockade with APV in kittens disrupts visual cortical plasticity, impairing orientation selectivity and preventing normal visual development during critical periods.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Visual System Plasticity
Background:
- The role of NMDA receptors in experience-dependent plasticity of the visual cortex is not fully understood.
- Understanding critical period plasticity is crucial for addressing visual developmental disorders.
Purpose of the Study:
- To investigate the specific role of NMDA receptors in visual cortical plasticity during the critical period.
- To determine if blocking NMDA receptors affects the development of orientation selectivity and visual responsiveness.
Main Methods:
- Continuous infusion of the NMDA receptor antagonist D,L-APV into the kitten striate cortex.
- Manipulation of the visual environment (monocular deprivation, reverse suture, dark-rearing) during the critical period.
- Single-unit recordings to assess neuronal orientation selectivity and visual responsiveness.
Main Results:
- APV infusion led to a concentration-dependent increase in neurons lacking orientation selectivity and responsive to the deprived eye.
- APV treatment prevented the normal development of visual selectivity and responsiveness after dark-rearing.
- Effects were stereospecific (D-APV) and outlasted drug presence, with no lasting effects observed in adult cats.
Conclusions:
- NMDA receptor blockade by APV specifically disrupts experience-dependent visual cortical plasticity in kittens.
- These findings support a critical role for NMDA receptors in the developmental refinement of visual cortical circuits.