FY2019 Annual Report

Brain Mechanisms for Behaviour Unit
Professor Gordon Arbuthnott

Abstract

This was a year of many interns.

The picture was taken when they were all here at once, although that did not happen for all the time of course.

Shannon Duke was an applicant for 2020 intake of Graduate Students and Anastasia Goryanin came for a short time from her studies in Edinburgh University Medical School. Karin Kinjo worked with us as part of studies for her first degree at the University of Paris Descartes; Fanny Denux came from Paris to work with us as part of degree studies at the Sorbonne and Nitsan Schwarz was trained in specialized mice stereotaxic surgery in Stanford before coming to learn immunocytochemistry with us.

 

1. Staff

• Dr. Marianela Garcia Munoz, Group Leader
• Dr. Esther Lai, Staff Scientist
• Dr. Junghyun Jo, Staff Scientist (Starting September 2019)
• Dr. Teresa Hernandez Flores, Researcher
• Dr. Hoan-Dai Tran, Researcher (Starting October 2019)
• Yoko Nakano, Technical Staff
• Nilipaer Abudukeyoumu, Graduate Student
• Bianca Sieveritz, Graduate Student
• Hiroko Chinone, Administrative Assistant

2. Collaborations

Nothing to report.

3. Activities and Findings

3.1 Graduated Students

After graduation Nilupaer left for a post-doctoral position at Professor Anita Disney’s neurobiology laboratory in the Center for Cognitive Neuroscience, Duke Institute for Brain Sciences, Duke University School of Medicine, we wish her well in achieving new challenges.
Bianca passed her exam for her PhD and will graduate in May. In June, she will start a post-doctoral position at Roozbeh Kiani’s Perceptual and Mnemonic Decision-making Laboratory in the Faculty of Arts and Science, New York University. (Bianca’s plans were interrupted by corona virus lockdown, so no graduation ceremony and a delayed move to the USA till August were the consequences.)

Meanwhile the two PhD theses still need their findings published in full.  Nilupaer’s  anatomical work is in preparation with some serious input from one of her examiners Dr Jill Crittenden, who has a different model of the death of the cholinergic cells in striatum. Bianca’s anatomical work is revised for publication too, though her behavioral results are still in the process of being analyzed, with work completed since her thesis was submitted.

3.2 Catching up with the backlog

This has been a year of recovery in output.  We have submitted several manuscripts and now have one Published.  Mainly the work was done while or just before I was Dean but the papers rely on our attention to details of the original experiments and their analysis.
The usual interpretation of the two sets of output cells from the input area of the basal ganglia suffered some hard knocks internationally and our own results added to its reconsideration.  We no longer support the idea that the two groups of striatal output neurons are inevitably antagonist to one another but work together to sculpt movement parameters. When dopamine is missing the dynamics of the two are completely distorted and fire in one large stereotyped group making the nuanced control of movement impossible.  We were able to show that such a situation, generated optogenetically in normal mice, also renders the animal unable to make normal movements.
 

This was the graphical abstract in European Journal of Neuroscience article (see publications)
Similarly, disrupting either group of striatal output neurons during a learned movement meant disruption in the success of the movement with direct cells involved in the reach through the hole in the chamber wall, while D2 cells were more involved in reaching the end point.

This one is submitted as the graphical abstract in our submission to Cell Reports.
Wish us luck!

3.3 We still also work in cortex

The final output of basal ganglia reaches layer 1 of the cortex via ventral thalamus.  That pathway has been our target in three studies all of which are approaching completion this year.  A study of the activity of the axons from thalamus to layer 1 is being analyzed in detail, the action of the pathway onto individual cortical cells in layer 1 has been contrasted with the input to the same cells from other areas of cortex.  Finally, we have looked at the influence of these layer 1 fibers in prelimbic cortex, on cost/benefit decision making in rats.  Bianca’s PhD Thesis is the only result for now, the papers will come.

3.4 Studies on human neurons

This year’s big news for the Unit is the arrival of Doctors Junghyun  Jo and Hoang-Dai Tran, from Singapore, with the aim to build human brain organoids in which to test theories of the causes of Parkinson’s Disease.  Much of what we have done in the field, has been oriented towards finding ways to ameliorate the devastating symptoms of the disease, but with these human derived cell cultures we hope to be able to attack the cause of dopamine loss rather than its consequences, i.e., why do dopamine neurons die?

 

4. Publications

4.1 Journals

1. Impaired reach-to-grasp responses in mice depleted of striatal cholinergic interneurons. Nilupaer Abudukeyoumu, Marianela Garcia-Munoz, Yoko Nakano, Gordon W. Arbuthnott Targeting Trends, 19, 1+6, 2019
    
2. Synchronized activation of striatal direct and indirect pathways underlies the behavior in unilateral dopamine‐depleted mice. Omar Jaidar, Luis Carrillo‐Reid, Yoko Nakano, Violeta Gisselle Lopez‐Huerta, Arturo Hernandez‐Cruz, Jose Bargas, Marianela Garcia‐Munoz, Gordon William Arbuthnott. European Journal of Neuroscience 49 1512-1528, 2019

4.2 Books and other one-time publications

Nothing to report

4.3 Oral and Poster Presentations

1. Bianca Sieveritz, Marianela Garcia Munoz, Gordon W. Arbuthnott.
   Ventral motor thalamic input to prelimbic cortex is involved in cost-benefit decision-making. Ninth International Symposium on Biology of Decision Making; Oxford May 27-29, 2019

2. Gordon W. Arbuthnott, Marianela Garcia Munoz. What if Parkinson’s Disease Symptoms are cortical? Annual Meeting of the Physiological Society Abstract 3557; Aberdeen July 7-10, 2019

3. Carlos Gutierrez, Jun Igarashi, Zhe Sun, Hiroshi Yamaura, Tadashi Yamazaki, Markus Diesmann, Jean Lienard, Heidarinejad Morteza, Benoit Girard, Gordon Arbuthnott, Hans Ekkehard Plesser, Kenji Doya. A whole‑brain spiking neural network model linking basal ganglia, cerebellum, cortex and thalamus. Annual computational neuroscience meeting CNS*2019; BMC Neuroscience 20 (Suppl 1): 56 P73; Barcelona. July 13-17, 2019

4. Esther. Lai, Gordon W. Arbuthnott. Inputs to neurons in layer 1 of mouse cerebral cortex. Society for Neuroscience Annual Meeting Abstract 2941: Chicago Oct 23, 2019

5. Teresa Hernandez Flores, Yoko Nakano, Andres Carrasco, Marianela Garcia Munoz, Gordon W. Arbuthnott. Direct measurement of striatal cholinergic transmission with a specific genetically encoded fluorescent acetylcholine indicator in mice. Society for Neuroscience Annual Meeting Abstract 3557; Chicago Oct 20, 2019

6. Bianca Sieveritz, Marianela Garcia Munoz, Gordon W. Arbuthnott. Ventral motor thalamic input prelimbic cortex is involved in cost-benefit decision-making. Gordon Research Seminar/Gordon Research Conference Ventura February 16-18, 2020

5. Intellectual Property Rights and Other Specific Achievements

Nothing to report

6. Meetings and Events

6.1 What if the symptoms of parkinsonism are cortical ? 

• Date: July 12, 2019
• Venue: Centre Discovery Brain Sciences, Edinburgh Medical School, Biomedical Sciences, University of Edinburgh
• Speaker: Prof. Gordon Arbuthnott

6.2 Towards induced pluripotent cell-derived sensory neurons for fate commitment of bone marrow stromal cell-derived Schwann cells and beyond.

• Date: July 1, 2019
• Venue: OIST Campus Lab1
• Speaker: Professor Daisy K. Y. Schum (Schoold of Biomedical Sciences, The University of Hong Kong)

6.3 Simultaneous two photon calcium imaging of cortical and striatal microcircuits.

• Date: February 17, 2020
• Venue: OIST Campus Lab 3
• Speaker: Dr Omar Jaidar Benavides (The Ding Lab, Stanford University School of Medicine, U.S.A.)

7. Other

Nothing to report.