Jean Rossier: Plasticity, Critical Period, Perineuronal Net (PNN), Metallopeptidases and Fast Spiking Parvalbumin (FS-PV) interneurons in the cortex
It is a great pleasure to invite you to attend a seminar by Professor Jean Rossier from INSERM, France. Dr. Rossier has made several major discoveries in neuropharmacology including his work on neuropeptides with Bloom, Guillemin, and Udenfriend. He discovered multiple opioïd peptides delineating several distinct neuronal systems involved in pain and reward. Turning his interests on GABAA receptors, he made the seminal observation that several inverse agonists facilitate performance in learning and memory tasks. This has led to the present development by the pharmaceutical industry of specific inverse agonists which are candidates for promnesic drugs. His most widely technical contribution in neuroscience is the invention of single cell RT-PCR after patch-clamp. This unexpected marriage of molecular biology and physiology led to several discoveries. With single cell RT-PCR, he has deciphered the molecular organization of various synaptic receptors. He is now using RT-PCR and a multidisciplinary approach combining electrophysiology, pharmacology and imaging to characterize the diversity of neocortical interneurons and their roles in local blood flow control.
The in situ hybridization Allen Mouse Brain Atlas was mined for proteases expressed in the somatosensory cerebral cortex. Among the 480 genes coding for protease/peptidases, only 4 were found enriched in cortical interneurons: Reln coding for reelin; Adamts8 and Adamts15 belonging to the class of metzincin proteases involved in reshaping the perineuronal net (PNN) and Mme encoding for Neprilysin, the enzyme degrading amyloid β−peptides. The pattern of expression of metalloproteases (MP) was analyzed by single cell RT multiplex PCR after patch-clamp and was compared with the expression of 10 canonical interneurons markers and 12 additional genes from the Allen Atlas.
Clustering of these genes by K-means algorithm displays five distinct clusters. Among these 5 clusters, two fast spiking (FS) interneurons clusters expressing the calcium-binding protein Pvalb were identified, one co-expressing Pvalb with Sst (PV-Sst) and another co-expressing Pvalb with three metallopeptidases Adamts8, Adamts15 and Mme (PV-MP). By using Wisteria Floribunda agglutinin, a specific marker for PNN, PV-MP interneurons were found surrounded by PNN while the one expressing Sst, PV-Sst were not. Recent studies on animal models of schizophrenia indicated that FS-PV interneurons surrounded by PNN are protected against oxidative stress.
The present study may indicate that FS-PV interneurons expressing Sst are not protected by PNN and represent a distinct class of FS-PV highly susceptible to oxidative stress.