FY2019 Annual report

Neuronal Rhythms in Movement (nRIM) unit
Assistant Professor Marylka Yoe Uusisaari

nRIM unit at the OIST CDC grounds. Top row (from left to right): Lakshmipriya Swaminathan, Saeko Hedo, yoe; Middle row, Salvatore Lacava, Guo Da; Front row: Rasmus Ingvarsson, Aysen Gurkan Ozer, Bogna Ignatowska-Jankowska, Kevin Dorgans, Alex Kuck. 

Abstract

In it's 3rd year of operations, the nRIM grew with new students and interns, and the research work in all 4 major projects is progressing with increasing speed. We hosted several high-profile seminars and took part in community outreach activities. 
Two key elements promoted throughout the year in our work relate to continuous improvement of 1) animal wellbeing and 2) laboratory safety. 

At the close of FY19, the global COVID-19 situation started affecting work, as we had to cancel several planned visits both to and from OIST, as well as by means of disruption of purchase deliveries. At the time of writing this report, nRIM is working following a plan to maximise short-term experimental data gathering in preparation for possible breaks in access to laboratories. However, we are well-set for productivity even during prolonged period of reduced presence in the laboratory.

1. Staff

• Dr. Alex Kuck, post-doctoral researcher (until July 2019)
• Dr. Da Guo, post-doctoral researcher
• Dr. Kevin Dorgans, post-doctoral researcher
• Dr. Bogna Ignatowska-Jankowska, JSPS fellow
• Dr. Aysen Gurkan Ozer, Technical Staff
• Mr. Salvatore Andrea Lacava, PhD student
• Ms. Saeko Hedo, Administrative Assistant (until June 2019)
• Ms. Lakshmipriya Swaminathan, PhD student
• Ms. Kayoko Ikeda, Administrative Assistant (Starting from Jan 2020)

2. Collaborations

External collaborations:

• The laboratory of Dr. Benjamin Cravatt, The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
• The laboratory of Dr. Sylvia Fitting at the Department of Psychology and Neuroscience at University of North Carolina, Chapel Hill
• Department of Biopharmacy at the Medical University of Lublin, Poland.
• Laboratory of Dr. Leonard Khiroug, University of Helsinki, Finland
• Laboratory of Dr. Andrea Giovannucci, University of North Carolina - Chapel Hill, USA
• Laboratory of Dr. Albert Chen, NTU Singapore
• Laboratory of Dr. Philippe Isope, INCI, CNRS, Strasbourg, France
• Dr. Aurelien Laguerre, OHSU, Portland, Oregon, USA
• Dr. Yunliang Zang, Brandeis University, Waltham, USA

Internal collaborations:

• Human neurobiology unit (Prof. Gail Tripp)
• Computational neuroscience unit (Prof. Erik De Schutter)
• Optical neuroimaging unit (Prof. Bernd Kuhn)

3. Activities and Findings

1. Project: Kinematic signatures of endocannabinoid function (Project leader: Dr. Ignatowska-Jankowska; other participants: Dr. Gurkan, Ms. Lakshmipriya Swaminathan): in FY19, the team conducted several large-scale experimental protocols, gathering data for finalizing the project for publication. Key findings obtained using the nRIM mouse MoCap system and presented at various conferences, include novel low-dose effects as well as bidirectional, task-dependent modulation of locomotion kinematics. The results will be presented at upcoming conferences (ICRS, FENS, SfN, depending on possibility).
2. Project: In vivo fluorescent imaging of inferior olive network activity (Project leader: Dr. Guo; supplementary research: Dr. Dorgans): in FY19, we managed to overcome several technical obstacles in reliable recording of the network activity in live mice, and manipulate their activity via optogenetic actuators. Importantly, the validity of the recordings are confirmed with parallel in vitro work. Experiments for the first publication are nearing completion, and results are to be presented at upcoming conferences (JNS, SfN if it will be organized as planned in 2020).
3. Project: In vitro investigation of calcium dynamics underlying subthreshold oscillations in the inferior olive (Project leader: Dr. Dorgans). In FY19, we have succeeded establishing and optimizing fluorescent imaging methods monitoring calcium dynamics in the inferior olive, and employed them to acquire several pilot data sets that will form the foundations of future projects. 
4. Project: Investigation of network dynamics with in vitro fluorescent imaging in the inferior olive  (Project leader: Dr. Dorgans). In FY19, the suitability of novel fluorescent voltage reporter dyes developed by the Optical neuroimaging unit were investigated in the context of subthreshold activity detection in the inferior olive. Results obtained in the last quarter of FY19 are now being finalized for methods paper. The project will then continue with in-depth investigation of coherent network activity.
5. Project: Motor signatures of ADHD in children (in collaboration with the Tripp unit). In this project we are examining the possibility that subtle differences in kinematic strategies among typically developing and ADHD children. In FY19, a proof-of-concept experiment was designed and pilot data obtained, and is currently analyzed for deciding further work directions.

4. Publications

4.1 Journals

1. Vrieler N., Loyola S., Yarden-Rabinowitz Y., Medvedev N., Hoogland T., De Zeeuw CI., De Schutter E., Yarom Y., Negrello M., Torben-Nielsen B., Uusisaari MY. Variability and directionality of inferior olive neuron dendrites revealed by detailed 3D characterization of an extensive morphological library. Brain Structure and Function 224: 1677-1695. doi: 10.1007/s00429-019-01859-z
2. Mustafa M, Donvito G, Moncayo L, Swafford A, Poklis J, Grauer R, Olszewska T, Ignatowska-Jankowska BM, Kendall D, Lu D, Lichtman AH. (2020) In vivo evaluation of the CB1 allosteric modulator LDK1258 reveals CB1-receptor independent behavioral effects. Pharmacol Biochem Behav, 190: 172840. doi:10.1016/j.pbb.2019.1728402.
3. Jacobs IR, Xu C, Hermes DJ, Xu C, Niphakis MJ, Cravatt BF, Mackie K, Lichtman AH, Ignatowska-Jankowska BM and Fitting S. (2019) Inhibitory control deficits associated with upregulation of CB1R in the HIV-Tat transgenic mouse model of HAND. J Neuroimmune Pharmacol, 14(4):661–678. doi:10.1007/s11481-019-09867-w3.
4. Donvito G, Piscitelli F, Muldoon P, Jackson A, Vitale RM, D'Aniello E, Giordano C, Ignatowska-Jankowska BM, Mustafa MA, Guida F, Petrie GN, Parker L, Smoum R, Sim-Selley L, Maione S, Lichtman AH, Damaj MI, Di Marzo V, Mechoulam R. (2019) N-Oleoyl-glycine reduces nicotine reward and withdrawal in mice. Neuropharmacology, 19; 148: 320-331. doi: 10.1016/j.neuropharm.2018.03.020.
5. Dorgans K, Demais V, Bailly Y, Poulain B, Isope P, Doussau F, Short-term plasticity at cerebellar granule cell to molecular layer interneuron synapses expands information processing. ELife. 2019 May 13;8. pii: e41586. doi:10.7554/eLife.41586.
6. Ozcan OO, Wang X, Binda F, Dorgans K, De Zeeuw C, Gao Z, Aertsen, KumarA, Isope P. Differential Coding Strategies in Glutamatergic and GABAergic Neurons in the Medial Cerebellar Nucleus. J Neurosci. 2020 Jan 2;40(1):159-170. doi:10.1523/JNEUROSCI.0806-19.2019. Epub 2019 Nov 6.
7. Straub I, Witter L, Eshra A, Hoidis M, Byczkowicz N, Maas S, Delvendahl I, Dorgans K, Savier E, Bechmann I, Krueger M, Isope P, Hallermann S. Gradients in the mammalian cerebellar cortex enable Fourier-like transformation and improve storing capacity.Elife. 2020 Feb 5;9. pii: e51771. doi: 10.7554/eLife.51771

4.2 Books and other one-time publications

1. Online database of inferior olive neurons published on neuromorpho.org http://neuromorpho.org/NeuroMorpho_ArchiveLinkout.jsp?ARCHIVE=Uusisaari&DATE=2019-12-13

4.3 Oral and Poster Presentations

1. Ignatowska-Jankowska BM, Kuck A, Uusisaari MY: Talk at CannX 4th International Medical Cannabis Conference, Tel Aviv, Israel. Kinematic signatures of cannabinoids in 3D motion capture in mice, 9-10 Sept 2019.
2. Ignatowska-Jankowska BM, Poster at 29th Annual International Cannabinoid Research Society Symposium on Cannabinoids. Bethesda, USA. (ICRS/NIDA Travel Award). 29 Jun-4 July19.
3. Guo D, Dorgans K, Uusisaari MY. In vivo calcium imaging of mouse inferior olive neurons. Cerebellum Conference GRC, Les Diablerets, Switzerland, July 14. - 19., 2019.
4. Synaptic operational rules for locomotor adaptation in the cerebellum. Spaeth L, Bahuguna J, Gagneux T, Petit-Desmoulieres N, Dorgans K, Sugihara I, Poulain B, Battaglia D and Isope P. Gordon Research Conference. July 14 - 19, 2019, Les Diablerets, Switzerland. Best poster award
5. Organization of the temporal coding rules of the sensorimotor information in the cerebellar modules. Rossi, Dorgans et al. Cerebellum Days, Strasbourg, January 2019. Best poster award
6. Gradients in the mammalian cerebellar cortex enable Fourier-like transformation and improve storing capacity. Straub I, Witter L, Eshra A, Hoidis M, Byczkow-icz N, Maas S, Delvendahl I, Dorgans K, Savier E, Bechmann I, Krueger M,Isope P, Hallermann S. Gordon conference, les Diablerets, July2019

4.4 Seminars at Research Institutes

4-5.09.2019: Workshop “Basics of rodent handling for researchers”, Neurotar, Helsinki, Finland.

4.09.2019: Emerging behavioral models: from 3D motion capture to behavioral transcriptomics”, University of Helsinki Helsinki, Finland

2.09.2019: “Emerging behavioral models: from 3D motion capture to behavioral transcriptomics”, Department of Neuroscience Erasmus University, Rotterdam, Netherlands.

22.07.2019: “Emerging behavioral models: from 3D motion capture to behavioral transcriptomics”. Lecture at the Nencki Institute of Experimental Biology, Warsaw, Poland.

5. Intellectual Property Rights and Other Specific Achievements

5.1 Awards

Bogna received the ICRS-NIDA travel award for attendance to ICRS annual meeting, 31 June-4 July 2019, Bethesda, USA ($675).

Bogna received the Judges Award for “My research in 200s” presentation “3D motion capture of freely behaving mice”, Researcher Appreciation Week, Okinawa Institute of Science and Technology (1 annual award, 3.03.2020)

Salvatore won the Research Fellowship for Young Scientist (JSPS DC-1) for the duration of 3 years starting from April 2020

6. Meetings and Events

6.1 Seminars hosted by nRIM unit

6.1.1 Molecular control of synapse identity and plasticity in cerebellar Purkinje cells

• Date: June 26st, 2019
• Venue: OIST Campus Lab1
• Speaker: Dr. Fekrije Selimi (CIRB, Collège de France)

6.1.2 Sound mechanism of Sanshin ~ Influence of Sao

• Date: July 8th, 2019
• Venue: OIST Campus Lab1
• Speaker: Dr. Kojiro Nishimiya (Aoyama Gakuin University, Japan)

6.1.3 Seminar: Mechanisms Linking Circadian Clocks to Sleep, Feeding Cycles, Seasonal Rhythms, and the Impact of Artificial Light at Night on Human Rhythms

• Date: Sept 17th, 2019
• Venue: OIST Center Building, C209
• Speaker: Fred Turek (Director of the Center for Sleep & Circadian Biology and Charles & Emma Professor of Biology in the Department of Neurobiology at Northwestern University)

6.1.4 Presidential Lecture: The molecular Circadian Clock and its impact on Health and Disease

• Date: Sept 18th, 2019
• Venue: OIST Center Building, B250
• Speaker: Fred Turek (Director of the Center for Sleep & Circadian Biology and Charles & Emma Professor of Biology in the Department of Neurobiology at Northwestern University)

6.1.5 Seminar: The cerebellum and Autism

• Date: February 18th, 2020
• Venue: OIST Center Building, C209
• Speaker: Prof. Yosef Yarom (Hebrew University of Jerusalem, Israel)

7. Other

7.1 Joint Cerebellar Journal Club

The joint journal club with specific focus on cerebellar research papers, with the Computational Neuroscience Unit and the Optical Neuroimaging Unit was extended with few members from other OIST units interested in olivo-cerebellar systems in FY 2019. During the year, the JCJC met 15 times, with presentations alternating between the laboratories.

7.2 Events at OIST

7.2.1. OIST Student Happy Hour

Bogna presented a seminar on "How and why to apply for travel grants” for OIST students

7.2.2. Assisting teaching in 'Physics for Life Sciences'

Salvatore was a TA for the class 'Physics for Life Sciences' taught by professor Bernd Kuhn (second term, Jan-Apr 2020), during which he gave presentations and organized hands-on sessions on optics and basic microscopy.

7.3 Community outreach activities

In FY19, several of the nRIM unit members volunteered in various community and science outreach projects, interacting with members of the public both in Okinawa and Japan.

7.3.1. Manai 2019 Programs

The Manai 2019 programs were organized by Manai Institute of Science and Technology for international high school students interested in science. The spring program was hosted by OIST in March. Dr. Da Guo help the program by giving a talk about optogenetic method in neuroscience study and a hands-on experience of 3D fluorescence microscopy.

The Manai summer program took place in Hokkaido University, from July 28^th to August 3^rd. Dr. Da Guo joined the program as a scientific mentor and planned a research project for a subset of students to investigate whether human thermal sensation can be influenced by other senses. He supervised the students through the research project including experiment design, execution, data analysis and presentation.

More information on the Manai program can be found here.

7.3.2 OIST Researcher Appreciation Week (March 2 - 6, 2020)

The nRIM unit members took active part in the first-ever RAW event week at OIST, by engaging in poster sessions, organizing lab tours and taking part in speech competition.