The differential expression of transcription factors during embryonic development has been selected as the main feature to define the specific subclasses of spinal interneurons. However, recent studies based on single-cell RNA sequencing and transcriptomic experiments suggest that this approach could not be appropriate in the adult spinal cord, where interneurons show overlapping expression profiles, especially in the ventral region. This constitutes a major challenge for the identification and direct targeting of specific populations that could be involved in locomotor recovery after a traumatic spinal cord injury in adults. Current experimental therapies including electrical stimulation, training, pharmacological treatments, or cell implantation that resulted in improvements in locomotor behaviour, rely on the modulation of the activity and connectivity of interneurons located in the surroundings of the lesion core for the formation of detour circuits. However, very few publications clarify the specific identity of these cells. In this work, we review the studies where premotor interneurons were able to create new intraspinal circuits after different kinds of traumatic spinal cord injury, highlighting the difficulties encountered by researchers to classify these populations.

The therapeutic effects of volatile anesthetics on mental diseases, particularly schizophrenia, have gained considerable interest. Although isoflurane is a commonly used volatile anesthetic, there’s no more evidence that it could work on treating schizophrenia. Here, we discovered that inhaling isoflurane at low concentrations might reverse the behavioral phenotypes of schizophrenia caused by MK801, such as hyperlocomotion, pre-pulse inhibition impairment, and working memory loss. Isoflurane also helped recovering adult neurogenesis and synaptic plasticity impairments in the dentate gyrus (DG) induced by MK801. To better understand the mechanism, we discovered that isoflurane could reverse the reduction of parvalbumin (PV)-positive GABAergic interneuron (PVI) number and the aberration of NRG1-ErbB4 signaling in the DG; however, isoflurane could not reverse the schizophrenia-related phenotypes caused by PVI ablation, indicating that PVI are necessary for the therapeutic effect of isoflurane. Interestingly, isoflurane could reverse phenotypes caused by blocking PVIs GABA release in the DG, indicating the therapeutic impact is independent of PVI GABA release. Our research revealed that isoflurane might be used to treat schizophrenia, possibly through PVI in the DG.

Excitation-inhibition imbalance of GABAergic interneurons is predisposed to develop chronic temporal lobe epilepsy (TLE). We have previously shown that virtually every neuronal nitric oxide synthase (nNOS)-positive cell is a GABAergic inhibitory interneuron in the denate gyrus. The present study was designed to quantify the number of nNOS-containing hilar interneurons using stereology in pilocapine- and kainic acid (KA)-exposed transgenic adult mice that expressed GFP under the nNOS promoter. In addition, we studied the properties of miniature excitatory postsynaptic current (mEPSC) and paired-pulse response ratio (PPR) of evoked EPSC in nNOS interneurons using whole cell recording techniques. Results showed that there were fewer nNOS-immunoreactive interneurons of chronically epileptic animals. Importantly, patch-clamp recordings revealed reduction in mEPSC frequency, indicating diminished global excitatory input. In contrast, PPR of evoked EPSC following the granule cell layer stimulation was increased in epileptic animals suggesting reduced neurotransmitter release from granule cell input. In summary, we propose that impaired excitatory drive onto hippocampal nNOS interneurons may be implicated in the development of refractory epilepsy.