INFLUENCE OF THE ELECTRICAL ACTIVITY ON SPECIFICATION OF NEURAL PROGENITORS OF THE ADULT SUBVENTRICULAR ZONE
Adult Neurogenesis; Subventricular Zone; Olfactory Bulb; Neuronal Specification
The Subventricular zone (SVZ) is the site of adult neurogenesis to the olfactory bulb (OB). SVZ progenitors generate mainly two types of interneurons that integrate in the OB: granular and periglomerular (PG) neurons. These cells can also be further subdivided based on the expression of the proteins calbindin, calretinin or tyrosine hydroxylase. The mechanisms that lead to the specification into these neuronal types are unknown. In the spinal cord neurogenesis, neurotransmitter identity is specified according to early spontaneous electrical activity in progenitor and precursor cells. This electrical pattern guide master transcription factors expression and the differentiation in a particular subtype. Manipulation of electrical activity can change de fate of progenitors and derived neurons. We hypothesize that the specification of SVZ-OB interneurons could also be influenced by electrical activity. To test this hypothesis, two experiments were designed to manipulate the cell electricity either acutely or chronicly. First, DCX-Cre-ER2/lox-GFP mice were injected with Kainic Acid (KA) or PBS in the neuroblasts migratory route to the bulb. Tamoxifen was injected 4 days after to label immature neuroblasts affected by KA and perfusion was performed 45 days after KA injection. In a second set of experiments, wild type mice were injected with a retrovirus containing the RNA for the expression of NaChBac, a bacterial sodium channel that increases electric activity. This channel is fused with the GFP that labels the infected cells. To control this experiment, a mutated non-functional version of the NaChBac channel was used. Cell identity was analyzed 45 days after injection. Our preliminary results suggest that the neuroblasts stimulated by the acute approach differentiate into TH+ PG neurons at the expense of Calbindin+ PG phenotype