Thalamocortical projections to the premotor cortex (PM) following unilateral lesion of primary motor cortex (M1) in macaque monkeys

Abstract

Voluntary movements, such manual dexterity with independent use of fingers, strongly depend on the corticomotoneuronal projection system in primates. Furthermore, the cortico-basal ganglia-thalamo-cortical and cortico-cerebello-thalamo-cortical loops contribute to shape motor commands for manual dexterity. The thalamocortical (TC) projections to multiple motor cortical areas represent a crucial terminal projection step underlying these two subcortical influences. The present study aimed at investigating whether the TC projection terminating in premotor cortex (PM) is affected following a lesion restricted to the homolateral primary motor cortex (M1) in adult macaque monkeys. The TC projections to PM were compared between intact monkeys (n=3) and monkeys subjected to a unilateral lesion of the homolateral M1 hand area (n=7), using the biotinylated dextran amine (BDA) retrograde tract-tracing method. The group of 7 lesioned monkeys was subdivided into a subgroup of 4 untreated subjects, while a subgroup of 3 subjects was treated with an anti-Nogo-A antibody. The BDA retrogradely labelled TC neurons projecting to PM were charted and quantified across different thalamic nuclei. The absolute total numbers of TC-stained neurons were considered for further analysis and inter-subgroups' comparison. As compared to intact monkeys, the TC projections' density in M1 lesion untreated monkeys was strongly reduced (about 6x less). In the anti-Nogo-A antibody treated subgroup (also M1 lesioned), the density of TC projection was less reduced (about 3x), as compared to intact monkeys. To minimize interindividual variability related to BDA injection sites' properties, the numbers of TC-stained neurons were normalized in each monkey based on the numbers of BDA labelled corticospinal (CS) axons. The normalization yielded comparable results as the absolute TC numbers, with however a more pronounced, actually complete separation between the 3 respective ranges of data points corresponding to the 3 monkeys' subgroups. In conclusion, the M1 lesion induced a sharp downregulation of TC projections to the homolesional PM, which was moderately minimized by the anti-Nogo-A antibody treatment.