Interview with Dr David Robbe conducted by April Cashin-Garbutt

Traditionally, the dorsal striatum has been thought to play a critical role in learning and selecting adaptive actions. However, recent research suggests that the dorsal striatum's contribution to action selection may be derived from its involvement in motivation.

In this Q&A, SWC Seminar speaker Dr David Robbe, Group Leader at Institut de Neurobiologie de la Méditerranée (INMED), shares his key findings and highlights how the dorsal striatum’s motivational function is relevant to understanding brain disorders such as Parkinson’s.

What role is the dorsal striatum believed to play in learning and procedural skills?

This is the debate! We think the dorsal striatum is critical for motor skills, learning, and procedural memory. But is this really the case? Could the dorsal striatum be contributing a component of behaviour necessary for learning motor skills, but not really be involved in motor skills themselves?

For instance, when we design experiments to test motor skill learning, we need to motivate the subjects, the animals. So that means in the task we use, there will be a motivational component. If the dorsal striatum is important in that motivational component, when we make a perturbation of the striatum we'll have a deficit of motivation, which will also show as a deficit in the motor skill. This is the confusion!

Do lesions of the basal ganglia output nuclei cause major memory and decisional impairments?

The basal ganglia consist of a set of connected nuclei. There is some input and there is some output. If you make perturbation in the input, you get an effect on behaviour. That's what is happening, for instance, in Parkinson's disease.

In Parkinson's disease, you have dysfunctioning of the dorsal striatum, because there's no more dopamine, and that leads to strong motor impairment. But surprisingly, in Parkinson's disease, if you lesioned the output of the basal ganglia, things get better.

You would think that if this place is important for motor coordination, then a lesion in the output would cause a large effect. But that’s not what we see. It’s a puzzle for the community.

How have you been examining the dorsal striatum and its contribution to action selection?

We do this by designing tasks where we can separate action selection, or procedural memory, from motivation. By doing this we see that if a task does not require a lot of motivation, the striatum perturbation or lesion doesn’t have much effect. 

And conversely, we've also done tasks in which we manipulate motivation. Then we see that lesion of the striatum impaired some motivational aspects, but not all of them.

Which animals have you studied this in, and do you think all animals optimise action cost (time plus effort) and reward in this way?

No, I wouldn't say all animals do this in the same way. But yes, all animals will be optimised. You can see this, for example, when you look at birds or any animal that is trying to get a reward, or food, sooner rather than later. 

This principle is very conserved across all animals. But of course, it's very different for a mouse compared to an elephant to move around. The costs are not the same. That means, for instance, mice are very impulsive and kind of hyperactive animals because their cost of movement is very limited. They're on the move all the time.

What have been your key findings so far and how does this relate to motivation?

Our key finding is to provide evidence that the dorsal striatum contributes to the sensitivity of effort not necessarily to motor memories. This is important because it allows us to link some of the observations in mice and rats with the type of deficits that we observe in Parkinson's disease, which are also related to effort sensitivity.

A common misconception is to think that Parkinson's disease is a purely motor deficit. But there is a clear motivational deficit in Parkinson's disease. The hypothesis is that people move more slowly or move less with Parkinson's disease because they're extremely sensitive to effort. This is implicit – they are not conscious that they are more sensitive to effort, but the body is telling them somehow that they should be more economical in their movement. 

This has been seen, for example, in people with Parkinson’s who find it difficult to walk but can play football, ice-skate, or cycle, and their movements are co-ordinated when they do that activity. This shows it is not a motor coordination problem alone. If you have a spinal cord lesion there are no contexts in which you can move.

That brings us to the possibility that there is context-dependent modulation of movement. Depending on the context, symptoms are going to be more or less present.

So why is this the case? We don't know yet - we don't entirely understand it. But one of the possibilities is that there is also a pleasure in doing those sports or activities. And that somehow compensates or allows the person to shift into a different state. So, imagine the disease causes you to overestimate the cost of your movement and then you can somehow counterbalance that by doing things that are very exciting. That’s a simplistic explanation, but it gives the idea of the issue we are looking at.

What is the next piece of the puzzle that you're hoping to solve?

Right now, to be honest, we've been using relatively crude methods to make perturbations in the striatum.  We've spent a lot of energy on developing behavioural tests in which we manipulate many things. 

The next step is to go back to physiology and look more at how the different sub-circuits of the basal ganglia could be important in different aspects of motivation.

Motivation is a very complex thing. There is a goal you want to achieve, to get your reward. But there is also effort, there is also more or less urgency. We want to try to understand motivation and the multi-component aspect of it better, and how different regions and circuits of the basal ganglia are contributing to that.

About Dr David Robbe

David Robbe is an INSERM research director and leads the "Cortico-Basal Ganglia Circuits and Behaviour" team at the Institute of Neurobiology of the Mediterranean (INMED, Marseille). After completing his PhD in Montpellier on the molecular determinants of synaptic plasticity in the ventral striatum, David Robbe did his postdoc in Gyorgy Buzsaki's lab where is studied study the relationship between neuronal population dynamics in the hippocampus and spatial memory. David Robbe then led a research team in Barcelona as part of the Ramon-y-Cajal program before joining INMED in 2012.

His current research aims to understand how economic constraints, such as time, effort, and expected rewards, influence both decision-making and movement speed, and how these modulations evolve depending on the animals' internal state and environment. Additionally, he investigates the role of the striatum in these behavioural modulations. To this end, his team develops ethologically inspired behavioural tests (e.g., foraging in freely moving rodents) and combines modelling with neurophysiological techniques (acute/chronic recording of neural ensembles, global/circuit-specific perturbation). His long-term goal is to better understand how motivational factors and neurobiological determinants interact to shape behaviour and how they may dysfunction in certain pathological conditions (depression, Parkinson’s disease, etc.), while avoiding as much as possible reductionism and the "brain a computing device" analogy.