GABAergic and glycinergic interneuron expression during spinal cord development: dynamic interplay between inhibition and excitation in the control of ventral network outputs.

A key objective of neuroscience research is to understand the processes leading to mature neural circuitries in the central nervous system (CNS) that enable the control of different behaviours. During development, network-constitutive neurons undergo dramatic rearrangements, involving their intrinsic properties, such as the blend of ion channels governing their firing activity, and their synaptic interactions. The spinal cord is no exception to this rule; in fact, in the ventral horn the maturation of motor networks into functional circuits is a complex process where several mechanisms cooperate to achieve the development of motor control. Elucidating such a process is crucial in identifying neurons more vulnerable to degenerative or traumatic diseases or in developing new strategies aimed at rebuilding damaged tissue. The focus of this review is on recent advances in understanding the spatio-temporal expression of the glycinergic/GABAergic system and on the contribution of this system to early network function and to motor pattern transformation along with spinal maturation. During antenatal development, the operation of mammalian spinal networks strongly depends on the activity of glycinergic/GABAergic neurons, whose action is often excitatory until shortly before birth when locomotor networks acquire the ability to generate alternating motor commands between flexor and extensor motor neurons. At this late stage of prenatal development, GABA-mediated excitation is replaced by synaptic inhibition mediated by glycine and/or GABA. At this stage of spinal maturation, the large majority of GABAergic neurons are located in the dorsal horn. We propose that elucidating the role of inhibitory systems in development will improve our knowledge on the processes regulating spinal cord maturation.