Our Research Interests
Nerve cells are connected to each other in intricate, but highly specific neuronal networks. Nerve cells communicate at synapses via the process of chemical synaptic transmission. Therefore, understanding how synaptic transmission is regulated by neuronal activity, and how synapses acquire their specific strength on correct partner neurons, is important to unravel the origins of information processing in the brain.
At most chemical synapses, transmission originates at the presynaptic nerve terminal by the quantal release of neurotransmitter, and presynaptic factors, such as the availability of readily-releasable vesicles, and presynaptic Ca2+ buffering and Ca2+ signaling influence synapse strength. Therefore, one focus of our work lies in understanding the cellular and molecular mechanisms that regulate Ca2+ signaling and Ca2+ dependent vesicle fusion in the nerve terminal.
Synaptic connections at specific sites in the brain must optimally fulfill the signaling needs of the circuit they are located in. For example, in the lower auditory (hearing) system, large excitatory synapses which can mediate an extremely fast and reliable depolarization of their postsynaptic neuron develop in specific areas. To understand how synapses acquire their specific properties during brain development, we investigate the signaling mechanisms and trophic factors which specify synapse size, synapse strength, and signaling speed during brain development. We recently showed that the bone morphogenetic protein (BMP) pathway is a major determinant of large synapse size and fast signaling properties in the auditory system (Xiao et al. 2013). We also investigate whether use-dependent synaptic plasticity can shape the wiring, and synaptic strength of excitatory and inhibitory synapses in sensory circuits. For these studies, we use the auditory system as a convenient model system. First, the auditory system shows a high degree of synapse size specificity, which is important for the computations performed in this system, like sound source localization. Second, sound representations in higher levels of the auditory system can be influenced by sensory experience, especially during critical periods of brain development.
Finally, in a third line of research, we are beginning to link synaptic pathways and synaptic plasticity in the forebrain limbic system, to motivated behavior of animals. In summary, our research aims to gain insight into neuronal – and synaptic network function in the context of sensory processing and the development of specific neuronal circuits. On the long term, our research should provide insight into the pathophysiology of neuropsychiatric and neurodegenerative disorders, many of which represent diseases of the synapse.