INVOLVEMENT OF MUSCARINIC ACETYLCHOLINE-RECEPTORS IN REGULATION OF KITTEN VISUAL-CORTEX PLASTICITY

Receptor autoradiographic methods specific for M(3) and M(1) muscarinic acetylcholine receptors were used to investigate the development and input-dependent laminar redistribution of these receptor populations during the critical period for kitten visual cortex plasticity. Analysis of the binding curves of [H-3]4-diphenylacetyl-N-methyl-piperidine (4-DAMP) and [H-3]pirenzepine (PZ) indicated that these two ligands bound heterogeneously to muscarinic acetylcholine receptors with different affinities. While [H-3]4-DAMP showed a high affinity for M(3) receptors and much lower affinities for M(1) and M(2) receptors, [H-3]PZ displayed higher affinity for M(1) receptors. By carefully choosing concentrations of labelled and unlabeled ligands, the patterns of laminar distribution for both receptor subtypes within visual cortex were obtained. Both receptors were most concentrated in cortical layer IV immediately after birth and during the most sensitive period of visual cortex plasticity. The binding density for both receptor subtypes thinned out progressively in this layer to concentrate in more superficial layers as plasticity waned with age. Moreover, interruption of visual or spontaneous input to visual cortex induced either by lesion or by tetrodotoxin infusion into lateral geniculate nucleus prevented the developmental redistribution of these receptors from layer IV to superficial layers, that is, the pattern of laminar distribution remained that of the age at which the lesion or tetrodotoxin infusion into the lateral geniculate nucleus was performed. The results indicate that the developmental expression of M(3) and M(1) muscarinic acetylcholine receptors in kitten visual cortex depends on cortical inputs. The parallel time course of these receptors' expression and laminar redistribution and their relation to the critical period of the developing visual cortex suggest that these muscarinic receptor classes may be involved in regulation of visual cortex plasticity.