Understanding how the brain processes new skills and actions can help to improve learning and aid research into neurodegenerative and psychiatric disorders such as Parkinson's and Huntington's disease. An EU-funded project has collected new data on the development of neural mechanisms of action learning and habit formation and addiction through the manipulation of the brain’s molecular networks. This could lead to breakthroughs in thought-controlled prostheses.
Some actions undertaken by living things are innate or pre-wired, such as swallowing, breathing and even grooming. Others are learned throughout life through trial and error. The EU-funded Neural mechanisms of action learning in mouse models (Neuroaction) project studied the neurological changes (changes in the brain, spinal cord and nervous system) which take place when actions are learned through the reaction to stimuli, facts and events.
The project’s findings give hope to sufferers of neurodegenerative conditions such as Parkinson's and Huntington's disease and could provide those who have suffered spinal cord injuries, amputations and other disabilities the possibility of regaining mobility through the use of thought-controlled prostheses.
The Neuroaction team sought answers on how the brain initiates and generates diverse actions; how it improves the accuracy and speed of actions through trial and error; and how the brain learns that particular actions lead to particular outcomes and goals, and how this contributes to forming habits. Humans learn initially in a goal-directed manner and then slowly it becomes a habit – an example of this could be driving your car home from work.
This was particularly interesting to the Neuroaction team in the context of their research into understanding the mechanisms underlying drug seeking in addiction.
“The results from this research will help us understand how we automatise skills and form habits, and how we make decisions in everyday life,” explains Dr Rui Costa, a researcher in the Neuroaction project. “They will also hopefully help us understand addictions – as many addictive drugs impinge on these circuits – and compulsions.”
The learning of new skills takes place in a specific part of the brain known as the striatum. However, the detailed mechanisms and circuits underlying the role of the striatum in the acquisition and consolidation of skills are not fully understood. The aim of the project, which is still ongoing, is to build a clearer picture of how the molecular networks in this area of the brain adapt. Results showed that the synapses in the connecting area between the striatum and the cerebral cortex (the area of the brain responsible for higher functions of the nervous system) exhibit long-term 'plasticity' during skill learning, a necessary adaptation in developing and retaining newly acquired skills.
“We wanted to investigate if the neural circuits responsible for our automated responses or habits were different to the neural circuits mediating our goal-directed or intentional actions,” says Dr Costa. “In particular, we wanted to know if different striatal circuits were mediating newly acquired versus automatised actions.”
The team found that circuits coursing through the dorsomedial striatum – the area of the striatum concerned with action selection and evaluation as well as in value-based decision-making – are more important for novel actions. In addition, circuits in the dorsolateral striatum – a different area of the striatum which deals with performance and habitual enactment of skills – are critical for automatised skills, such as driving your car home from work or riding a bike.
The project team also believes that the dorsolateral striatum has the potential to be trained, which could lead to the control of implanted prosthetic devices. Their findings might open the door to the development of thought-controlled prostheses restoring normal mobility levels for people with spinal cord injuries, amputations and other disabilities.
In addition, Neuroaction investigated the possible links between dysfunction in the striatum and cerebral cortex, and neurodegenerative conditions such as Parkinson's and Huntington's disease. “The links we’ve found are that cells that die in Huntington´s and Parkinson´s disease are abundant in the areas necessary for automatisation and habit formation,” explains Dr Costa.
Using specialised equipment and resources, the team carried out tests into neural activity in region-specific areas of the striatum during the different phases of skill learning in genetically modified mice.
Learning from the animals
The modified mouse genetics allowed the team to target specific circuits, while the use of optogenetics (a combination of optics and genetics techniques to control the activity of individual neurons – nerve cells which transmit information in living tissue) – enabled the researchers to manipulate such circuits with great precision. The activity of those brain circuits was then monitored by electrophysiology (the study of the electrical properties of biological cells and tissues).
“Our approach was to have a task where animals can learn and automatise novel skills, and manipulate circuits to investigate the neural bases of these processes,” Dr Costa says.
The initial findings from these tests provided important data on the processes of skill learning and execution, and on the development of impairments observed in neurodegenerative and psychiatric disorders. “We found that different circuits do indeed mediate the initial acquisition of actions and the automatisation of those actions,” continues Dr Costa. “We also discovered that dopamine from neurons in the part of the brain called the substantia nigra pars compacta is important for this automatisation and habit formation.” Dopamine is a neurotransmitter that helps control the brain’s reward and pleasure centres, while the substantia nigra pars compacta plays an indirect role in motor control.
The project NEUROACTION’s work is financed to the tune €100 000 by the Marie Curie Actions, an EU research fund managed by the Research Executive Agency (REA). Dr Rui Costa has also received a ‘Starting grant’ from the European Research Council (ERC) of around €1.5 million for the project NEUROHABIT to pursue his research.
Neuroaction’s research into the link between neural circuits and behaviour will continue under the Human Brain Project (HBP) which has been announced as one the EU’s Future and Emerging Technologies Flagship Projects. The HBP will run from 2013 until 2023. Researchers, including Dr Costa, will be tasked with producing data on complex systems within the brain and developing computational models of these systems.