Brain Mechanism for Behaviour Unit (Gordon Arbuthnott)
Professor Gordon Arbuthnott
gordon at oist.jp
- Marianela Garcia Munoz, Group Leader
- Esther S.K. Lai, Staff Scientist
- Teresa Hernandaz Flores, Researcher
- Yoko Nakano, Technician
- Hiroko Chinone, Research Administrator
Our aim is to understand, at the systems neuroscience level, the mechanisms that allow the brain to control behavioural responses. It now seems likely that the neurotransmitter, dopamine, has a vital role to play in this regard. However, the brain mechanisms underlying the changes in behaviour that can be engendered by training, remain obscure. We use anatomical, physiological, pharmacological and molecular genetic techniques to understand how dopamine acts on neuronal systems to change learning and performance. The endeavour will be a collaborative one involving other scientists at OIST in testing behaviour, in delineating the biology of the neural systems involved, and in developing theoretical models of brain systems capable of modifying behavioural outcomes.
Recently we showed that the synapses on the major output neurons of the striatum can be reduced in number by removal of dopamine and are doubled in number in mice lacking one class of calcium channels. We have so far only been able to show the anatomical effect at the two extremes, but in normal brain we expect this structural action of dopamine to play an important role in the normal sculpting of striatal cell assemblies to match the physiological requirements of changing motor strategies. Recent work on the consequences of behavioural training on synaptic networks in striatum are strengthening that expectation. We aim to continue to link synaptic physiology with behavioural outcomes.
Continuing work on the mechanisms of action of Deep Brain Stimulation for Parkinson’s disease and on the detailed anatomy and physiology of the basal ganglia will use electrophysiological and optogenetic approaches to increase our understanding of how these phylogenetically old brain structures operate. We were among the first to recognise that the final output of the basal ganglia arrives in layer 1 of the cerebral cortex. Optogenetic methods will now allow us to manipulate these layer 1 inputs to the cortex and asses their influence on functional cortical activity.
We developed a cell culture system, where only the corticostriatal system is present. Such a system allows us to ‘grow’ neuronal assemblies more like the networks modelled in mathematical simulations. Electrophysiological as well as imaging methods applied to these ‘simple’ networks allowed us to test some of the assumptions in mathematical simulations. Collaborations with several of the physics units are bringing to bear information-theoretical analyses and new methods of recording the results of activity in the brain.
Dopamine neurons are implicated in a wide variety of neurological and psychiatric disease states and we hope that our scientific knowledge of their basic biology will both, allow a deeper understanding of their role in these diseases, and suggest treatment strategies that respect the complex systems of which they form such a vital part.