cortex

Project number:

303

Project title:

Brain carbonic anhydrases in neuronal signaling, plasticity and epilepsy

Project supervisor:

Claudio Rivera/Kai Kaila

Project description:

Recent work has shown that neuronal signalling, especially GABAergic transmission, is strongly affected by carbonic anhydrase CAVII that is expressed in neurons. Data obtained at the level of purified CA molecules have shown that a number of amines as well as carboxylic acids have a strong modulatory action on the effective turn-over of CAs, including CAVII. However, there is little data available on the physiological and pathophysiological modulation of CAVII by amines and carboxylic acids in neurons.
We will examine the efficacy of CAVII using established techniques (laboratory of K. Kaila), where isolated neurons are exposed to step changes in the ambient carbon dioxide level, while measuring the changes in intracellular pH as an indicator of CAVII function. The effects of various kinds of biologically relevant amines (e.g., monoamine transmitter compounds) and end-products of energy metabolism (carboxylic acids) will be tested. In a next set of experiments, these results will be used to design experiments in order to find out the quantitative and qualitative role of such modulatory actions at the level of GABAergic signalling. This study may open up truly novel insights into (1) the actions of modulatory transmitter compounds and (2) the links between neuronal energy metabolism and plasticity. The experiments require a careful analysis of the regional and subcellular patterns of CAVII expression, that will be studied in the laboratory of Ole Petter Ottersen.

Possible cortex partners rotation:

Erlend Nagelhus/Ole Petter Ottersen, Oslo
Schmitz/ Dirnagl, Berlin