Ramanathan D, Conner JM, Anilkumar AA, Tuszynski MH (2010) Early post-natal cholinergic lesion impairs normal development and maturation of the motor cortex in rats. Neuroscience 2010 Abstracts 32.14/D20. Society for Neuroscience, San Diego, CA.
Summary: Prior studies have indicated that sensory and motor representations develop over a defined postnatal period and are dependent upon behavioral experience to achieve appropriate adult patterns. In adult animals, behaviorally driven forms of cortical map plasticity are critically dependent upon the basal forebrain cholinergic system. Based on the critical role cholinergic mechanisms play in mediating experience-dependent plasticity in adulthood, we postulated that cholinergic mechanisms may also play a critical role in shaping initial cortical map formation during development. In this study, using 25 male Fisher rats between the ages of 15 days and 60 days, we first characterized the normal motor map development in the rat. We found that motor maps underwent a significant change in overall size and refinement over time, with more mature animals having larger overall maps (p < 0.001) and an increase in the size of distal forelimb representations (p < 0.01). Following the initial characterization of normal motor map development in the rat, we used 192-IgG-saporin (SAP) to create selective cholinergic lesions early in map development (PND 24), in 5 animals (with 6 animals receiving ACSF as controls). This early cholinergic depletion impaired the normal maturation and refinement of cortical motor representations: the total caudal forelimb area (comprising elbow and wrist) was decreased by 33% in cholinergically depleted animals, from 5.1 ± 0.3 mm2 to 3.4 ± 0.3 mm2 (t-test p < 0.01). This decrease in caudal forelimb area in cholinergically-depleted animals was primarily driven by a significant 37% reduction in the size of the distal forelimb (wrist) representation, from 3.1 ± 0.1 mm2 to 2.0 ± 0.1 mm2 (p < 0.001). In a follow-up experiment with 12 additional animals (6 with cholingeric lesions and 6 controls), we found that early (PND 24) cholinergic depletions resulted in long-term impairments in skilled motor learning, with significant differences in daily motor performance beginning at day 3 of training (repeated measures ANOVA < 0.05). These results suggest a novel role for the basal forebrain cholinergic system in establishing normal cortical map formation during development.
Related Products: 192-IgG-SAP (Cat. #IT-01)