Periodic Reporting for period 1 - BRONC (Behavioral demand-driven dynamic reorganisation of cortical networks revealed by simultaneous wide-field optical imaging and optogenetic stimulation mapping in task-performing mice)
Reporting period: 2018-11-01 to 2020-10-31
We can change our thoughts and behavior flexibly to survive in the changing world. However, it remains to be elucidated how our brain achieves such flexible behavior. The goal of this project has been to uncover the mechanisms of such behavioral flexibility from a view point of neural circuits. Mammalian brain is subdivided into functionally differentiated small areas. The brain areas are anatomically connected by the axon fibers of neurons to communicate information. The anatomical connections are mostly fixed through the development, and do not change in adulthood. But adult animals can still behave very flexibly depending on different situations, and do not necessarily show a stereotypical response even when they encounter the same object. To enable such flexible behavior with the fixed anatomical connections, one possible way would be to modify the efficiency of the communication among brain areas to form a tailored circuit for behavior on demand. To examine such a possibility, I studied the brain of mice learning and executing a behavioral task where they reported whisker tactile perception by tongue movements, and revealed that the communication among brain areas was selectively enhanced and suppressed to form a temporary circuit executing necessary computation in the task context. The achievement of this project founded an important basis to further investigate the detailed mechanisms of rapid modification of brain circuits.
First, I developed paradigms where mice learned to detect a stimulation to a whisker, report the detection by licking a spout, and obtain the water reward. Next, I developed a combined wile-field optical imaging and laser scanning system, and established transgenic mice which co-express a genetically encoded neural activity sensor and a light-gated neural activator. These technical achievements made it possible to observe the activity of genetically-defined types of neurons, manipulate them to examine their causal roles, and visualize their information transmission among cortical areas (Figure 1). By systematically activating different areas by the laser scanning, I identified a motor area controlling movements of tongue and jaw (Figure 1A), which showed a sharp change of the causal control on licking across task learning. When mice learned the whisker stimulus predicting reward, the optical imaging revealed that the cortical responses to the same whisker stimulus changed drastically, evoking a sequential activation and deactivation in specific cortical areas including the motor area of tongue and jaw (Figure 1B). Optical inactivation of those areas revealed that their causal roles drastically changed across different task periods. These results demonstrated that the information flowed differentially in the cortical circuits depending on the task demands. To further investigate the changes in the cortical circuits, I started to systematically measure the communication efficiency among cortical areas by visualizing the propagation of the activity evoked by a short laser pulse (Figure 1C). This experiment is revealing how cortical circuits are tailored for specific behavior. I presented these results in conferences in Europe, United States and Japan, which were evaluated highly as evidenced by selection for short talks and travel awards. I published/submitted the reports with open access rights to enhance broad discussion and further usage of the project data in the basic scientific community.
Publications
1. Esmaeili V=1,*, Tamura K=1,* (=1, equal contribution; *, co-corresponding), …, Petersen C*. Divergent sensory processing converges in frontal cortex for a planned motor response. bioRxiv DOI: 10.1101/2020.10.06.326678.
2. Esmaeili V, Tamura K, …, Petersen C. Cortical circuits for transforming whisker sensory information into goal-directed licking. Curr Opin Neurobiol 65: 38-48 (2020).
1. Mayrhofer JM, …, Tamura K, Petersen C. Distinct contributions of whisker sensory cortex and tongue-jaw motor cortex in a goal-directed sensorimotor transformation. Neuron 103: 1–10 (2019). Data repository: https://doi.org/10.5281/zenodo.3271408.
Presentations (selected)
1. Tamura K, …, Petersen C. Cortical signal flow during sensorimotor transformation in a whisker detection and delayed lick task. Barrels XXXIII. (Online. Oct 21 – 23, 2020). Selected for short talk.
2. Tamura K, …, Petersen C. Global changes in cortical processing through learning of a delayed response behavior. NEURO2020 (Online, July 29 - Aug 1, 2020). Poster Movie (LBA-037).
3. Tamura K, …, Petersen C. Learning-induced changes in global cortical processing for a delayed response behavior. 12th FENS Forum for Neuroscience (Online, Jul 11-15, 2020), ePoster. FENS Virtual Forum Grant.
4. Tamura K, …, Petersen C. Changes in global cortical processing induced by learning of a delayed response behavior. 22nd SSN Annual Meeting (Bern, Switzerland, Feb 22, 2020), Poster.
5. Tamura K, …, Petersen C. Optical measurement and perturbation of global cortical processing for context-dependent behavior. Neuroscience 2019 (Chicago, USA. Oct 19-23, 2019), Selected for Nanosymposium (Oral). SfN Trainee Professional Development Award.
6. Tamura K, …, Petersen C. Revealing context-dependent global cortical processing by wide-field calcium imaging and optogenetic stimulation mapping. NEURO2019 (Niigata, Japan. Jul 25-28, 2019). Selected for Short Talk.
7. Tamura K, …, Petersen C. Global cortical processing for context-matched behavior revealed by optogenetic stimulation mapping and wide-field calcium imaging. EMBO|EMBL Symposium (Heidelberg, Germany. Apr 10-13, 2019). Selected for Short Talk.
8. Tamura K, …, Petersen C. Context-driven global cortical processing revealed by optogenetic stimulation mapping and wide-field calcium imaging. 21st SSN Annual Meeting (Geneva, Switzerland. Feb 1, 2019). Poster.
9. Tamura K, …, Petersen C. Context-dependent changes in global cortical processing revealed by wide-field calcium imaging and optogenetic stimulation mapping. BMI Symposium (Lausanne, Switzerland. Dec 3-4, 2018). Poster.
Publications
1. Esmaeili V=1,*, Tamura K=1,* (=1, equal contribution; *, co-corresponding), …, Petersen C*. Divergent sensory processing converges in frontal cortex for a planned motor response. bioRxiv DOI: 10.1101/2020.10.06.326678.
2. Esmaeili V, Tamura K, …, Petersen C. Cortical circuits for transforming whisker sensory information into goal-directed licking. Curr Opin Neurobiol 65: 38-48 (2020).
1. Mayrhofer JM, …, Tamura K, Petersen C. Distinct contributions of whisker sensory cortex and tongue-jaw motor cortex in a goal-directed sensorimotor transformation. Neuron 103: 1–10 (2019). Data repository: https://doi.org/10.5281/zenodo.3271408.
Presentations (selected)
1. Tamura K, …, Petersen C. Cortical signal flow during sensorimotor transformation in a whisker detection and delayed lick task. Barrels XXXIII. (Online. Oct 21 – 23, 2020). Selected for short talk.
2. Tamura K, …, Petersen C. Global changes in cortical processing through learning of a delayed response behavior. NEURO2020 (Online, July 29 - Aug 1, 2020). Poster Movie (LBA-037).
3. Tamura K, …, Petersen C. Learning-induced changes in global cortical processing for a delayed response behavior. 12th FENS Forum for Neuroscience (Online, Jul 11-15, 2020), ePoster. FENS Virtual Forum Grant.
4. Tamura K, …, Petersen C. Changes in global cortical processing induced by learning of a delayed response behavior. 22nd SSN Annual Meeting (Bern, Switzerland, Feb 22, 2020), Poster.
5. Tamura K, …, Petersen C. Optical measurement and perturbation of global cortical processing for context-dependent behavior. Neuroscience 2019 (Chicago, USA. Oct 19-23, 2019), Selected for Nanosymposium (Oral). SfN Trainee Professional Development Award.
6. Tamura K, …, Petersen C. Revealing context-dependent global cortical processing by wide-field calcium imaging and optogenetic stimulation mapping. NEURO2019 (Niigata, Japan. Jul 25-28, 2019). Selected for Short Talk.
7. Tamura K, …, Petersen C. Global cortical processing for context-matched behavior revealed by optogenetic stimulation mapping and wide-field calcium imaging. EMBO|EMBL Symposium (Heidelberg, Germany. Apr 10-13, 2019). Selected for Short Talk.
8. Tamura K, …, Petersen C. Context-driven global cortical processing revealed by optogenetic stimulation mapping and wide-field calcium imaging. 21st SSN Annual Meeting (Geneva, Switzerland. Feb 1, 2019). Poster.
9. Tamura K, …, Petersen C. Context-dependent changes in global cortical processing revealed by wide-field calcium imaging and optogenetic stimulation mapping. BMI Symposium (Lausanne, Switzerland. Dec 3-4, 2018). Poster.
The experimental system I developed for laser scanning and wide-field imaging in combination with the advanced transgenic mouse technology is providing a new vision for neural circuits: systematic catalogue of causal interaction among cortical areas, or causal connectome. The analysis of the dynamics of the causal connectome for different behavioral demands is updating the understanding of the functional multiplexity and stability of the mammalian brain circuits. The deactivation of specific cortical areas by the task learning is providing a novel concept that both enhancement and suppression of the cortical signal transmission are involved in the learning and execution of a simple behavior. These results have shifted the state-of-the-art of the field of systems neuroscience. Future studies based on the project results will allow mechanistic understanding of the flexibility of animal behavior, and further contribute to the field of psychiatry by inspiring a study to understand and control the obsessive symptoms to specific thoughts and behavior from a view point of circuit flexibility, which will provide a positive impact on the society.