1. Performing two-photon calcium imaging of head-direction cells in RSC.
A large dataset comprising thousands of cells across mouse RSC was obtained during passive rotation. In this dataset, 5-10% of cells were found to show head direction tuning, and remarkably many of these cells also showed conjunctive tuning to other features such as turn direction, and speed. Summaries of these results were presented in conference abstracts at two major international meetings: (1) European Visual Cortex meeting in London, UK, and (2) Society for Neuroscience meeting in Washington, DC, USA.
2. Computational analysis of head direction tuning in RSC.
In collaboration with a computational neuroscientist, analysis of the dataset from Topic 1 revealed the extent to which individual RSC head direction cells can decode head direction alongside other features of passive rotation. Experimental data also shows the stability of head direction tuning over multiple days of imaging. This analysis will be presented at an international conference for memory research (Spring Hippocampal Research Conference, Taormina, Italy). These results are also being prepared into a manuscript for publication.
3. Development of an active rotation behavioral task to study the causal impact of RSC in head-direction perception.
Since only a minority of cells in the RSC are sensitive to head direction, we developed a task that would allow high-resolution imaging of head direction cell activity during active conditions, as opposed to passive rotation. In the task, mice were trained to orient themselves toward visual or auditory cues and discriminate between the direction of these cues. Therefore, the task required the development of a new behavioral paradigm that can be used to understand how mice used directional information to orient themselves in space. Preliminary experiments also included performance of the task during periods when the RSC was inactivated with a drug, however more experiments are needed to determine the effect of RSC inactivation on behavioral measures.
4. Development of viral-genetic strategies to determine mechanistic underpinnings of RSC head-direction tuning.
Another aspect of the project was to develop viral-genetic strategies to identify how RSC head-direction cells obtain their functional properties. To this end, mouse lines which allowed the study of different neuronal cell types such as inhibitory and excitatory neurons in RSC, and the isolation of specific inputs to RSC from other memory and sensory related areas, were studied under two conditions: (1) passive rotation, and (2) memory consolidation periods in awake and sleeping mice. Cell-type specific responses in both experiments indicate that certain cells mediate different aspects of memory and navigation, and that these cells could be unique therapeutic targets for treatment of memory-related diseases. These results will be presented at two international conferences: (1) The Spring Hippocampal Research Conference (Taormina, Italy), and (2) The Society for Neuroscience Meeting (Chicago, USA). The results are also being prepared into a manuscript for publication.
