PhD student, Erasmus Medical Center
Sensorimotor integration in the thalamus modulates movement coordination
The sensorimotor system of our body is essential for the execution of precise movements that enable us to move freely through our daily lifes. To safely maneuver through the environment the brain needs to compare active sensory information with ongoing fine-tuned motor programs. Several brain nuclei co-process sensory- and motor-related inputs and malfunctioning of these integrative centers leads to impaired motor and sensory processing and thus motor disease. At the higher level of sensorimotor integration, brain structures such as sensory and motor cortices integrate information and form output centers for motor programs. The cerebellum, supports the proper execution of motor plans by encoding accurate timing and fine-tuning of movements. Within the motor system, the most suitable candidate nucleus for cortico-cerebellar convergence and integration is the thalamic ventro-lateral nucleus (VL), as it receives direct synaptic input from cerebellar nuclei neurons but also feedback from primary motor cortex. Synaptic inputs to the thalamus can be subdived into drivers and modulators. Driver synapses are characterized by large ionotropic receptor mediated evoked post-synaptic currents with decreasing amplitudes while modulatory synaptic currents are evoked by metabotropic receptors, show small but increasing amplitudes upon sustained higher frequency activity. We want to proof that modulatory synapses from M1 and driver synapses from CN do converge onto single cells in VL and thus mediate thalamo-cortical activity patterns for sensorimotor integration. Therefore, we established an in-vitro optogenetic dual-channel photostimulation approach in combination with whole-cell patch clamp recordings, which allows us to excite cortical and cerebellar synaptic populations independently by using blue (470nm) and orange (585nm) light excitation. The physiological response pattern of motor cortical and cerebellar synapses as well as the combined stimulation of both inputs allows us to identify synaptic properties as well as mechanisms of synaptic integration in the thalamus and the sensorimotor system.
Abstract: Optogenetic tools enable examination of how specific cell types contribute to brain circuit functions. A long-standing question is whether it is possible to independently activate two distinct neural populations in mammalian brain tissue. Such a capability would enable the study of how different synapses or pathways interact to encode information in the brain. Here we describe two channelrhodopsins, Chronos and Chrimson, discovered through sequencing and physiological characterization of opsins from over 100 species of alga. Chrimson's excitation spectrum is red shifted by 45 nm relative to previous channelrhodopsins and can enable experiments in which red light is preferred. We show minimal visual system-mediated behavioral interference when using Chrimson in neurobehavioral studies in Drosophila melanogaster. Chronos has faster kinetics than previous channelrhodopsins yet is effectively more light sensitive. Together these two reagents enable two-color activation of neural spiking and downstream synaptic transmission in independent neural populations without detectable cross-talk in mouse brain slice.
Pub.: 11 Feb '14, Pinned: 08 Aug '17