FY2018 Annual Report

Brain Mechanisms for Behaviour Unit
Professor Gordon Arbuthnott

(From left to right) Esther Lai, Bianca Sieveritz, Marianela Garcia Munoz, Gordon Arbuthnott, Hiroko Chinone, Teresa Hernandez Flores, Nilupaer Abudukeyoumu, Yoko Nakano

Abstract

This year has been my return to the laboratory full time, though the new Dean and the massive recruiting effort for new Professors in OIST have taken some time.

Nevertheless, we have two reviews accepted for the IBAGS special issue of the European Journal of Neuroscience and a long experimental paper also in EJN that presents a new image of the control of striatal microcircuits in Parkinson’s Disease models in mice.

There are many more in various stages of preparation so the Unit is firing on all cylinders again.

 

1. Staff

  • Marianela Garcia Munoz, Group Leader
  • Esther Suk King Lai, Staff Scientist
  • Teresa Hernandez Flore, Researcher
  • Yoko Nakano, Technical Staff
  • Nilupaer Abudukeyoumu, Graduate Student
  • Bianca Sieveritz, Graduate Student
  • Hiroko Chinone, Research Unit Administrator

 

2. Collaborations

2.1 Optical probe for deep brain recordings

  • Description: Research work on optical probe by graduate student, Simon Peter Mekhail.
  • Type of collaboration: Joint research
  • Researchers:
    • Professor Sile Nic Chormaic, OIST Graduate Univerity, Light-matter Interactions Unit

2.2 Calcium dynamics in brain slices

  • Description: Analysis methods for calcium activity in neurons in acute slices.
  • Type of collaboration: Continuing joint research
  • Researchers:
    • Professor Luis Carrillo-Reid, National Autonomous University of Mexico

 

3. Activities and Findings

Nilupaer completed her Ph.D. and the poster we wrote and presented for her in Society for Neuroscience meeting won a first prize, for papers on specific immunotoxins.

Nilupaer’s results from her Ph.D. are being prepared for publication. It looks like we have some data that will help assigning a functional role to the cholinergic striatal interneurons soon.

Bianca is working on a manuscript that describes the anatomical work she has completed that will be vital as part of the behavioural experiments she is in process of finishing.

We have learned to use GRIN lenses and have been working to prefect the use of them with multicore fibers with The Light Matter Interactions Unit; Peter Mekhail is writing his thesis on that topic. Yoko Nakano has made us some really useful virus constructs that might allow us to measure the release of neurotransmitters in vivo.

Figure 1: Histological section from the striatum of a mouse showing the position of the GRIN lens. The internal capsule fibers that penetrate the striatum are black and have been distorted somewhat during the implantation. The red and green bright dots are cells labelled by Virus infection with a CGAMP6S calcium indicator. The astroglial scar tissue is stained blue with an antibody to glial fibrillary acid protein.

 

Teresa has confirmed Violeta’s results that suggest that striosomes are not connected to the rest of the striatum, in a new transgenic mouse that was bred in OIST by Professor Doya’s Unit. The SEPW1 mice have cells outside the striosome areas that their originator calls ‘exopatch’ neurons.  These may be genetically similar to the striosomal cells but may not connect in the same way, more time will tell.  Her cortical work on calcium imaging is nearing the final analysis it has taken some careful experimental studies to collect the data but with help from Luis Carrillo Reid we should be able to put the results together for publication. Luis was here for a week both to help with those projects but also to share some plans about the development of the ‘cell assembly’ project he has developed in his postdoctoral work in New York.



Figure 2:The photomicrograph shows the cells in the Sepw1 mouse slice, stained with an AAV virus containing ChannelRhodopsin2. Most of the striosomes are not in focus but show as red fluorescent areas. Many of the cells that show clearly are outside the striosomes and called ‘exopatch’ cells by Prof Gerfen, who generated this mouse.

 

Finally, we are still fascinated with Layer1 of cortex. Esther is using new Optical tools that have allowed us to study the influence of thalamic and other inputs into Layer 1 of motor cortex.  The inhibitory interneurons in layer 1 are certainly influenced by more than one input and we are exploring the differences not only in the kinds of neuron there but also their different responses to input fibers. Although there are now some publications detailing the effects of these surface thalamic inputs on the deeper cells in cortex there are still many aspects of the ‘Crowning Enigma’ that will keep us busy for another year.

Marianela was involved closely in preparing and writing the short paper to the Tokyo conference on Neurology but she takes an active part in designing experiments and a major part in all the publications from the Unit. Her input has been vital in the scientific output of the Unit.

 

4. Publications

4.1 Journals

1. Arbuthnott, G.W. & Munoz, M.G. (2018) A Cortical Substrate for Parkinsonism: A Personal Journey. International Journal of Clinical Research & Trials, 3, 1-4.

2. Mekhail, S.P., Abudukeyoumu, N., Ward, J., Arbuthnott, G. & Chormaic, S.N. (2018) Fiber-bundle-basis sparse reconstruction for high resolution wide-field microendoscopy. Biomedical Optics Express, 9, 1843.

3. Abudukeyoumu, N., Hernandez-Flores, T., Garcia-Munoz, M. & Arbuthnott, G.W. (2018)   Cholinergic modulation of striatal microcircuits. Eur J Neurosci.

4. Sieveritz, B., Garcia-Munoz, M. & Arbuthnott, G.W. (2018) Thalamic afferents to prefrontal cortices from ventral motor nuclei in decision-making. Eur J Neurosci.

In Press

1. Jaidar, O., Carrillo-Reid, L., Nakano, Y., Lopez-Huerta, V.G., Hernandez-Cruz, A., Bargas, J., Garcia-Munoz, M. & Arbuthnott, G.W. (2019) Synchronized activation of striatal direct and indirect pathways underlies the behavior in unilateral dopamine-depleted mice. Eur J Neurosci.

2. Abudukeyoumu, N., Garcia-Munoz, M., Nakano, Y., Arbuthnott, G.W. (2018) Impaired reach-to-grasp responses in mice depleted of striatal cholinergic interneurons. Targeting Trends

4.2 Books and other one-time publications

Nothing to report

4.3 Oral and Poster Presentations

A role for motor thalamus in decision-making
Bianca Sieveritz, Marianela García-Muñoz, Gordon W. Arbuthnott
ENCODES  2017

Ventromedial thalamic projection neurons to prelimbic cortex in cost-benefit decision-making
Bianca Sieveritz, Marianela García-Muñoz, Gordon W. Arbuthnott
SfN annual meeting San Diego,2018

Impaired reach-to-grasp responses in mice depleted of striatal cholinergic interneurons
Nilupaer Abudukeyoumu , Marianela Garcia-Munoz , Yoko Nakano, Gordon Arbuthnott
SfN annual meeting San Diego,2018

Absence of direct synaptic connectivity between striatal compartments in identified striosome neurons
Teresa Hernandez-Flores, Yoko Nakano, Marianela Garcia-Munoz, Gordon Arbuthnott
SfN annual meeting San Diego,2018

Inputs to neurons in layer 1 of mouse cerebral cortex    
Esther Lai, Marianela Garcia Munoz, Gordon Arbuthnott
SfN annual meeting San Diego,2018 146.22 / JJ8

Cell assemblies in the striatum; the source of intentional movement.
Gordon Arbuthnott
Invited talk at KAIST 'Future of Medicine' Meeting Daejeon, South Korea 2018

What if Parkinson’s Disease Symptoms are cortical?
Gordon Arbuthnott, Marianela Garcia Munoz
Invited talk at International Conference on neurovascular and Neurodegenerative Diseases (NVND-2018) Tokyo, Japan 2018

 

5. Intellectual Property Rights and Other Specific Achievements

Nothing to report

6. Meetings and Events

6.1 Manipulation of behavioral performance induced by targeted activation of cortical ensembles

  • Date: March 20, 2019
  • Venue: OIST Campus Lab3
  • Speaker: Prof. Luis Carrillo-Reid, National Autonomous University of Mexico

 

7. Other

Nothing to report.