Plastic changes in the cholinergic innervation of the rat cerebral cortex after unilateral lesion of the nucleus basalis with α-amino-3-OH-4-isoxozole propionic acid (AMPA): Effects of basal forebrain transplants into neocortex

• Published in: Brain research bulletin 1997, Vol.42 (2), p.79-93
• Main Authors: Calaminici, Mariarita, Abdulla, Fuad A., Sinden, John D., Stephenson, John D.
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase-positive fibres; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - pharmacology; AMPA; Animals; Biological and medical sciences; Cerebral Cortex - metabolism; Cerebral Cortex - physiology; Cerebral Cortex - surgery; Choline O-Acetyltransferase - metabolism; Choline-acetyltransferase; Development. Senescence. Regeneration. Transplantation; Excitatory Amino Acid Agonists - pharmacology; Fetal Tissue Transplantation; Fundamental and applied biological sciences. Psychology; Male; Nerve Tissue - embryology; Nerve Tissue - transplantation; Neuronal Plasticity; Nucleus basalis; Parasympathetic Nervous System - physiology; Prosencephalon - drug effects; Prosencephalon - embryology; Prosencephalon - physiology; Rats; Rats, Sprague-Dawley; Transplantation; Vertebrates: nervous system and sense organs
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/S0361-9230(96)00212-2

Unilateral AMPA lesions of the nucleus basalis magnocellularis (nbm) produced a nearly complete loss of cholinergic markers in the ipsilateral frontal and parietal cortices with no recovery at 6 months. The loss was associated with compensatory increases in AChE-positive fibre density in the contralateral cortex, in ipsilateral cortical regions not receiving their cholinergic innervation from the nbm and in the size of cholinergic magnocellular neurones in the contralateral nbm. The hypertrophy and increase in AChE-positive fibre density were apparent at 4–6 weeks after lesion and increased with time. Cholinergic transplants to cholinergically deafferented cortex prevented development of the compensatory increases in AChE-positive fibre density and restored AChE-positive fibre density and ChAT activity to control levels in ipsilateral cholinergically deafferented regions, partially after 6–8 weeks and completely after 6 months. In contrast, when cholinergic grafts were placed into unlesioned cortex, axonal outgrowth was localized to the vicinity of the transplant and did not develop with time. These results support the concept that vacant synapses promote and direct axonal outgrowth from transplanted neurones and that grafted cholinergic neurones integrate into the lesioned forebrain cholinergic projections system and prevent the lesion-induced changes in AChE-positive fibre density and ChAT activity.