Inhibitory Synaptic Influences on Developmental Motor Disorders

During development, GABA and glycine play major trophic and synaptic roles in the establishment of the neuromotor system. In this review, we summarise the formation, function and maturation of GABAergic and glycinergic synapses within neuromotor circuits during development. We take special care to discuss the differences in limb and respiratory neuromotor control. We then investigate the influences that GABAergic and glycinergic neurotransmission has on two major developmental neuromotor disorders: Rett syndrome and spastic cerebral palsy. We present these two syndromes in order to contrast the approaches to disease mechanism and therapy. While both conditions have motor dysfunctions at their core, one condition Rett syndrome, despite having myriad symptoms, has scientists focused on the breathing abnormalities and their alleviation-to great clinical advances. By contrast, cerebral palsy remains a scientific quagmire or poor definitions, no widely adopted model and a lack of therapeutic focus. We conclude that the sheer abundance of diversity of inhibitory neurotransmitter targets should provide hope for intractable conditions, particularly those that exhibit broad spectra of dysfunction-such as spastic cerebral palsy and Rett syndrome.

Automated summary

During development, GABA and glycine play important roles in the neuromotor system, affecting the formation, function and maturation of synapses. This review focuses on GABAergic and glycinergic synapses in neuromotor circuits, discussing the differences in limb and respiratory control. It also explores the effects of GABAergic and glycinergic neurotransmission on two developmental neuromotor disorders, Rett syndrome and spastic cerebral palsy, highlighting the different approaches to disease mechanism and therapy. The article concludes that the diversity of inhibitory neurotransmitter targets offers hope for treating conditions like spastic cerebral palsy and Rett syndrome that exhibit a wide range of dysfunctions.