  |
 |
 |
Inhibitory Circuits Control Experience-Dependent
Plasticity in Developing Visual Cortex
Laboratory for Neuronal Circuit Development |
|
|
|
Sensory experience in early life shapes the mammalian brain. After even a brief period of monocular occlusion in early life, input to visual cortex from the closed eye is functionally weakened, then anatomically reduced in size. How perturbed levels of neuronal activity are detected to produce changes in connectivity within cortex remains unknown.
We have recently identified an impairment in the activity-dependent refinement of functional connections within developing visual cortex in a mouse model (Hensch et al, Science 282: 1504).
|
- |
Intracortical Inhibition Sets the Threshold for Experience-Dependent Plasticity.
(magnify:27k)
|
|
Gene-targeted disruption of one isoform of the GABA-synthetic enzyme, glutamic acid decarboxylase (GAD), prevented the competitive loss of responsiveness to an eye briefly deprived of vision, without affecting cooperative mechanisms of synapse modification in vitro. Selective intracortical enhancement of fast inhibitory transmission with benzodiazepines restored plasticity in vivo, rescuing the genetic defect. Competitive plasticity in vivo, therefore, requires a threshold level of GABAergic transmission, making it fundamentally different from in vitro LTP or LTD models that are impeded by inhibition.
Our results indicate that local cortical circuits instruct the expression of changes in both thalamocortical and intracortical connections that are known to accompany monocular deprivation. A delicately balanced recruitment of excitation and inhibition detects the disparity between competing sensory inputs and drives experience-dependent changes in visual cortex (figure). Our findings identify the first animal model that is immune to perturbations of sensory input, exhibiting a robust yet reversible disruption of plasticity in the intact visual cortex. This provides a valuable tool for dissecting the unique local circuit properties that enable experience-dependent plasticity in the developing brain.
|
Hensch, T.K., Fagiolini, M., Mataga, N., Stryker, M.P., Baekkeskov, S., Kash, S.F.
Local GABA circuit control of experience-dependent plasticity in developing visual cortex.
Science 282: 1504-1508 (1998).
|
|
 |
 |
|
|
|
