Cell-type-specific molecular plasticity in the Mesencephalic Locomotor Region is necessary for motor memory consolidation.

It is classically thought that motor memories are formed through neuronal plasticity in higher motor centres, such as the motor cortex, cerebellum, and basal ganglia, while downstream motor regions primarily execute learned motor commands. However, we hypothesize that the formation of new motor skills also requires plastic changes in brainstem centres, such as the Mesencephalic Locomotor Region (MLR), to adapt motor commands to new task demands. The MLR comprises the pedunculopontine (PPN) and cuneiform (CnF) nuclei, containing glutamatergic (Glu-MLR), GABAergic and cholinergic (ChAT-MLR) populations. Using mice, different motor training tasks and cell-type specific pharmacogenetic approaches, we found that de novo protein synthesis in Glu-MLR neurons is necessary for the consolidation of newly learned motor tasks. Moreover, in situ analysis of the MLR in mice that successfully learned these tasks revealed increased expression of proteins involved in signalling pathways classically associated with learning and memory in higher motor centres and with different types of memory, suggesting that these molecular mechanisms are highly conserved. We are now addressing the in vivo electrophysiological correlates of these molecular changes and whether ChAT-MLR neurons also contribute to motor memory consolidation. Our findings challenge the classic view of downstream motor regions, demonstrating that Glu-MLR neurons undergo molecular plasticity required for motor memory consolidation.