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Discovery may shed light on mechanisms behind addiction and Parkinson’s

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Researchers in the US have gained new insight on the pathway between the reward centre of the brain key to how we form habits and the region responsible for motor learning.

The New Jersey Institute of Technology (NJIT) researchers say the connection between the the basal ganglia and the cerebellum potentially changes our fundamental view of how the brain processes voluntary movements and conditioned learning.

They believe that this may lend fresh insight into the neural mechanisms underlying addiction and neurodegenerative diseases like Parkinson’s.

Farzan Nadim is chair of NJIT’s Department of Biological Sciences.

The researcher said: “We are exploring a direct communication between two major components of our brain’s movement system, which is absent from neuroscience textbooks.

“These systems are traditionally thought to function independently.

“This pathway is physiologically functional and potentially affects our behaviours every day.”

While both subcortical structures have long been known for their separate roles in co-ordinating movement through the cerebral cortex, they are also critical to both conditioned and error-correction learning.

The basal ganglia,  described by Nadim as the “brain’s go-no-go system” for determining whether we initiate or suppress movement, is also involved in reward-based learning of behaviour triggered by the release of dopamine.

Nadim said: “It’s the learning system that promotes motivated behaviour, like studying for a good grade.

“It’s also hijacked in cases of addiction.

“On the other hand, every behaviour that we learn — whether it’s to hit a baseball or play violin — this motor learning is happening in your cerebellum at the back of the brain. It’s your brain’s optimisation machine.”

However, the researchers’ latest research suggests the cerebellum could be involved in both.

In their study, Nadim and his colleagues sad they have reported the first direct evidence that the two systems are intertwined — showing the cerebellum modulates basal ganglia dopamine levels that influence movement initiation, vigour of movement and reward processing.

Nadim said: “This connection starts at the cerebellum and goes to neurons in the midbrain that provide dopamine to the basal ganglia, called the substantia nigra pars compacta.

“We have brain recordings showing this signal is strong enough to activate the release of dopamine within the basal ganglia.

“This circuit may be playing a role in linking the cerebellum to motor and nonmotor dysfunctions.”

The researchers are seeking to identify exactly where cerebellar projections to the dopamine system originate at the nuclei level, a key step in learning whether the function of this pathway can be manipulated, Nadim said.

However, the their findings so far could have research implications for neurodegenerative diseases like Parkinson’s, which is associated with the death of dopamine-producing neurons in the substantia nigra.

Nadim said: “This pathway seems very important to our vigour of movement and speed of cognitive processes.

“Parkinson’s patients not only suffer from suppression of movement, but apathy in some cases.

“The cerebellum’s location at the back of the brain makes it a much easier target for novel therapeutic techniques, such as non-invasive transmagnetic or direct-current stimulation.

“Since we’ve shown the cerebellum is directly exciting dopamine neurons in the substantia nigra, we might now use mouse models for Parkinson’s to explore such techniques to see if that jumpstarts activity of these neurons and relieves symptoms of the disease.”

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