RESUMO
The present study explores the impact of metabotropic glutamate receptor (mGluR) activation on activity-dependent synaptic plasticity (ADSP) and the intrinsic membrane properties of lumbar motoneurons (MNs) using a combination of biochemical, pharmacological, electrophysiological and behavioral techniques. Using spinal cord slices from C57BL/6JRJ mice at two developmental stages, 1-3 and 8-12 postnatal days (P1-P3; P8-P12, respectively), we found that ADSP expressed at glutamatergic synapses between axons conveyed in the ventrolateral funiculus (VLF) and MNs, involved mGluR activation. Using specific agonists of the three groups of mGluRs, we observed that mGluR stimulation causes subtype-specific and developmentally regulated modulation of the ADSP and synaptic transmission at VLF-MN synapses as well as the intrinsic membrane properties of MNs. RT-qPCR analysis revealed a downregulation of mGluR gene expression with age in the ventral part of the lumbar spinal cord. Interestingly, the selective harvest by laser microdissection of MNs innervating the Gastrocnemius and Tibialis anterior muscles unraveled that the level of Grm2 expression is higher in Tibialis MNs compared to Gastrocnemius MNs suggesting a specific mGluR gene expression profile in these two MN pools. Finally, we assessed the functional impact of mGluR modulation on electrically induced bouts of fictive locomotion in the isolated spinal cord preparation of P1-P3 mice, and in vivo during spontaneous episodes of swimming activity in both P1-P3 and P8-P12 mouse pups. We observed that the mGluR agonists induced distinct and specific effects on the motor burst amplitudes and period of the locomotor rhythms tested and that their actions are function of the developmental stage of the animals. Altogether our data show that the metabotropic glutamatergic system exerts a complex neuromodulation in the developing spinal lumbar motor networks and provide new insights into the expression and modulation of ADSP in MNs.
RESUMO
This article aims to review studies that have investigated the role of neurons that use the transmitter acetylcholine (ACh) in controlling the operation of locomotor neural networks within the spinal cord. This cholinergic system has the particularity of being completely intraspinal. We describe the different effects exerted by spinal cholinergic neurons on locomotor circuitry by the pharmacological activation or blockade of this propriospinal system, as well as describing its different cellular and subcellular targets. Through the activation of one ionotropic receptor, the nicotinic receptor, and five metabotropic receptors, the M1 to M5 muscarinic receptors, the cholinergic system exerts a powerful control both on synaptic transmission and locomotor network neuron excitability. Although tremendous advances have been made in our understanding of the spinal cholinergic system's involvement in the physiology and pathophysiology of locomotor networks, gaps still remain, including the precise role of the different subtypes of cholinergic neurons as well as their pre- and postsynaptic partners. Improving our knowledge of the propriospinal cholinergic system is of major relevance to finding new cellular targets and therapeutics in countering the debilitating effects of neurodegenerative diseases and restoring motor functions after spinal cord injury.
