Renshaw cell interneuron specialization is controlled by a temporally restricted transcription factor program.

The spinal cord contains a diverse array of physiologically distinct interneuron cell types that subserve specialized roles in somatosensory perception and motor control. The mechanisms that generate these specialized interneuronal cell types from multipotential spinal progenitors are not known. In this study, we describe a temporally regulated transcriptional program that controls the differentiation of Renshaw cells (RCs), an anatomically and functionally discrete spinal interneuron subtype.

Regulation of gephyrin cluster size and inhibitory synaptic currents on Renshaw cells by motor axon excitatory inputs.

Renshaw cells receive a high density of inhibitory synapses characterized by large postsynaptic gephyrin clusters and mixed glycinergic/GABAergic inhibitory currents with large peak amplitudes and long decays. These properties appear adapted to increase inhibitory efficacy over Renshaw cells and mature postnatally by mechanisms that are unknown. We tested the hypothesis that heterosynaptic influences from excitatory motor axon inputs modulate the development of inhibitory synapses on Renshaw cells.

Pax6 and engrailed 1 regulate two distinct aspects of renshaw cell development.

Many of the interneuron cell types present in the adult spinal cord contribute to the circuits that control locomotion and posture. Little is known, however, about the embryonic origin of these cell types or the molecular mechanisms that control their differentiation. Here we provide evidence that V1 interneurons (INs), an embryonic class of interneurons that transiently express the En1 transcription factor, differentiate as local circuit inhibitory interneurons and form synapses with motor neurons.

Glycine and GABA(A) receptor subunits on Renshaw cells: relationship with presynaptic neurotransmitters and postsynaptic gephyrin clusters.

Inhibitory synapses with large and gephyrin-rich postsynaptic receptor areas are likely indicative of higher synaptic strength. We investigated the presynaptic inhibitory neurotransmitter content (GABA, glycine, or both) and the presence and subunit composition of GABA(A) and glycine postsynaptic receptors in one example of gephyrin-rich synapses to determine neurochemical characteristics that could also contribute to enhance synaptic strength. Hence, we analyzed subunit receptor expression in gephyrin patches located on Renshaw cells, a type of spinal interneuron that receives powerful excitatory and inhibitory inputs and displays many large gephyrin patches on its surface.