The functional properties of local neuronal microcircuits determine the computational capacity of specialized brain structures and drive animal behaviour. The cerebellum is a specialized anatomical structure that is involved in the learning and execution of motor coordination.
It contains only a handful of morphological cell types that have been extensively characterized. Theoretical calculations and computer modeling studies have suggested several ways in which the connectivity and physiological activity might be translated into motor control.
However, experimental validation of the input-output function of the cerebellar microcircuit is still lacking. We propose an original experimental paradigm to unravel how the cerebellar cortical circuit processes incoming sensory-motor inputs in its input layer. First, we will mimic physiological cortical inputs in a reduced preparation of the vestibulo-cerebellum. Secondly, we will monitor simultaneously the activity of multiple identified neurons within the circuit in situ.
To this end we will use an innovative multi-photon microscope that has been developed in the sponsor's laboratory in Paris. This unique device, based on acousto-optic deflectors-operated beam steering, performs 250 kHz digital scanning as well as digital photon counting.
It is a promising tool to perform long-duration optical multiunit recordings (50 cells) with millisecond temporal resolution in situ. Additionally, the improved spatial and temporal resolution afforded by acousto-optical beam steering allows distributed excitation of hundreds of points in a plane.
Combining this technology with glutamate uncaging will allow us to study integration of synaptic inputs by stimulating controlled physiological patterns of neuronal excitation that mimic cortical inputs. Together, these innovative techniques bear great promise to improve our understanding of the computational dynamics in brain structures.
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