L-VGCC subtypes during development of inhibitory and excitatory circuitry in the central auditory system.

University of Oldenburg, Germany

Processing of auditory information such as pitch, intensity, and location, requires a convergence of morphological, biophysical, and biochemical specializations in auditory neurons. Specific features include the most precise timing of action potentials found within the brain, giant synaptic structures and a great number of processing centers connected via a pleiotropy of ascending and descending pathways.

Our research focuses on two main processing centers within the auditory brainstem: the Superior Olivary Complex (SOC) and the Inferior Colliculus (IC). The SOC is involved in binaural sound localization by comparing interaural level and time differences. The IC is a central hub for ascending and descending auditory pathways. The main lines of research in our group relate to the development of these two auditory centers and to the identification of molecular mechanisms underlying processing of auditory information.

We mainly work with rodents (rat, mouse and gerbil) and mammalian cell cultures. Methods include a large range of different molecular, biochemical and genetic techniques such as yeast to hybrid system, microarray technology, proteomics, and generation of transgenic animals.

Role of CaV1.3 in the development of auditory brainstem structures

The depolarizing action of inhibitory neurotransmitters in immature neurons is likely required to trigger Ca2+-dependent signaling cascades leading to strengthening of synaptic connections. One of the major entry gates for Ca2+ in postsynaptic neurons are voltage-gated calcium channels.

Expression analysis indicated strong expression of CaV1.3 in the auditory pathway and CaV1.3 knockout mice display a structural abnormal SOC. To investigate further the role of CaV1.3 in the development of the SOC, we currently generate a regional-specific CaV1.3 knockout mouse using the bacterial artificial chromosome (BAC) technique.