|Ph.D Student||Lavzin Maria|
|Subject||Network and Single Cell Mechanisms Underlying|
|Department||Department of Medicine||Supervisor||Professor Jackie Schiller|
In this work we concentrated on sensory-motor processing in cortical neurons. Understanding sensory-motor representation and processing is important to our understanding of how we translate sensation to action. We sought out to explore these mechanisms in-vivo using two different approaches.
In the first part of the thesis we studied sensory processing in the primary somatosensory cortex of rats (the barrel cortex) in an in-vivo anesthetized animal preparation. We used the rat whisker system that is considered an excellent model for the study of sensory processing due to the very clear mapping between the sensory periphery and the cortex. Although many cellular mechanisms have been described and much has been learned about the computational power of single cortical pyramidal neurons in-vitro, very little is known about the cellular mechanisms used by the single neurons under physiological conditions in-vivo. We studied the contribution of nonlinear dendritic mechanisms, which previously had only been described in-vitro, to the sensory selectivity properties of single cortical neurons in-vivo. To that end, we studied the angular tuning responses of layer 4 spiny stellate neurons in the barrel cortex. We performed whole-cell recordings of layer 4 neurons in the barrel cortex in-vivo, while applying different sensory stimulation paradigms to the whiskers and specific blockers for NMDAR. Contrary to the prevailing dogma, we found that the NMDAR dendritic regenerative responses critically contribute to the selectivity properties of layer 4 spiny stellate neurons in the rat barrel cortex. This part of the work was published (Lavzin et al. 2012, appendix 1).
In the second part of the thesis we developed a novel experimental platform to study the neural mechanisms underlying motor behavior and motor learning in the primary motor cortex of awake behaving mice. The motor system possesses an ability to learn new skills to adapt to new and varying environments and training can improve the effectiveness of voluntary movements. The mechanisms underlying these changes remain unclear. Classically, these questions were studied mainly by fMRI experiments in human subjects or single unit recordings from primates. However, the low resolution of these methods and the lack of cell type specificity do not allow us to infer the underlying cellular and network mechanisms. The motor system is complex, involving many cortical and sub-cortical areas and each area is comprised of several cell types. Thus, in order to fully understand the circuit, we need to study the activity of identified neuronal types within the network. In this project we concentrated on layer 2-3 and layer 5 pyramidal tract neurons. We developed an experimental platform enabling us to record the activity of several hundreds of neurons with cellular and sub-cellular resolution. We used calcium imaging of genetically encoded indicators to chronically record from the same neurons over many weeks using two-photon imaging. These calcium imaging recordings were made in head restrained mice performing a hand reach task under the microscope. Our first findings show significant differences in the activity of layer 2-3 neurons vs. layer 5 during the hand reach task.