Rodenas Ruano, Alma Ph.D.

Epigenetic regulation of the cation-chloride symporter KCC2 during neuronal development.

  • Fordham University
  • 2016
Rodenas Ruano, Alma Ph.D.
Brain function is based on the balance of excitation and inhibition. This balance is set early in development via the switch of GABAergic and glycinergic transmission from excitatory to inhibitory. In most vertebrate neurons, this change from depolarizing to hyperpolarizing function is mediated by changes in Cl- gradients generated by an increase in the expression of the cation-Cl- symporter KCC2, which extrudes Cl- from neurons. While it is known that increased KCC2 expression is causal to the excitation/inhibition shift, very little information exists on the transcriptional mechanisms that regulate its developmental expression in vivo. Transcriptional regulators act through epigenetic modifications to modify gene expression, and serve as the link between gene-environment interactions. In the studies proposed here using a zebrafish model, the aim is to identify the epigenetic mechanisms that contribute to the KCC2-mediated developmental switch that leads to inhibitory function in mature neurons. I will use biochemical, physiological, and imaging approaches in control and genetically modify zebrafish spinal and brainstem neurons. My goal for the Grass Fellowship is to determine what epigenetic mechanisms are required for the acquisition of inhibitory function in mature vertebrate neurons.

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