Effects of cholinergic depletion on experience-dependent plasticity in the cortex of the rat

Abstract

Clinical and functional studies have strongly suggested that acetylcholine input from the nucleus basalis of Meynert is important for the cortex's adaptive response to experience. The purpose of this study was to investigate the effects of depletion of acetylcholine inputs from nucleus basalis of Meynert on experience-dependent plasticity in the cortex of young adult male rats. The posteromedial barrel subfield in the primary somatosensory cortex was studied. Experience-dependent plasticity was elicited using a whisker-pairing paradigm in which all whiskers except D2 and D3 were trimmed daily. Plasticity within barrel D2 of the posteromedial barrel subfield was measured using the electrophysiological extracellular recording technique. An index of plasticity was determined in two ways: as an increase in the magnitude of evoked activity to stimulation of whisker D2 and as a bias in the ratio of evoked activity for stimulation of paired whisker D3 and cut whisker D1 (D3/D1). Whiskers D2, D3 and D1 were stimulated (deflected) by a Chubbuck electromechanical stimulator. Cholinergic neurons in the nucleus basalis of Meynert were selectively lesioned with an immunotoxin, 192 IgG-saporin, injected into the left lateral ventricle. Lesions of cholinergic neurons in the nucleus basalis of Meynert were verified using choline acetyltransferase immunocytochemistry and radioenzymatic assay. Experience-dependent plasticity was significantly reduced in cholinergic-depleted animals. The magnitude of evoked activity to stimulation of whisker D2 increased by 16-100% in control animals compared with 0-20% in cholinergic-depleted animals. Similarly, compared to a 60-100% increase in the D3/D1 ratio of evoked activity for phosphate-buffered saline-injected control animals, cholinergic-depleted rats showed no significant increase in the D3/D1 ratio (0-15%) after undergoing the whisker-pairing paradigm. After whisker trimming, the D3/D1 response ratio in immunotoxin-treated animals was essentially the same as in control animals that had not been subjected to the whisker-pairing paradigm. This study showed that no significant plasticity response was observed in the absence of cholinergic input from the nucleus basalis of Meynert. The mechanisms of the action of acetylcholine in cortical plasticity are still not known, but we hypothesize that this type of plasticity is activity dependent and is significantly enhanced in the presence of acetylcholine.