(Image caption: Inside the basal ganglia (highlighted in pink), neurons compete for the brain’s decisions. New research indicates this mechanism favors “no” as our default response. Credit: Wikimedia Commons)
A new computational model based on data from rodent brains shows that “Go” and “No-Go” signals compete in the brain, originating from the nerve cells in the striatum – a part of brain that plays a crucial role in decision making, learning and various motor functions. But, the deck is stacked against the Go neurons, which are expressed in D1 type dopamine receptors, says Arvind Kumar the senior author of the study and a researcher at the Department of Computational Biology at KTH Royal Institute of Technology.
“It could be that humans are wired to be natural naysayers,” Kumar says. The reason is that the D1 (Go) neurons and their rival D2 (No Go) neurons are projected in pathways within the striatum that inhibit each other. “However, it turns out that the No-Go pathway exerts more inhibition on the Go pathway than vice versa,” he says.
“This inherent bias creates the decision transition threshold for the kind of input that is likely to change your preference,” Kumar says. “One way to adjust the threshold is through learning. Another way is with neuromodulators like dopamine.”
The bias in this threshold is due to an asymmetrical connection between the two circuits of neurons, in which the No Go pathway is stronger. Therefore, D1 neurons require slightly higher input. However, with this setting, D1 neurons can overcome the No Go pathway only when they receive weak inputs from the cerebral cortex that generates functions such as sensory perception, motor command, conscious thought and language. The switch between Go or No-Go decisions, depending on cortical input, gives rise to the decision transition threshold.
“This threshold where you are likely to switch your decision from Go to No Go, is created by unequal connectivity. If the connectivity were identical then such a threshold would not arise.” says Jyotika Bahuguna, the lead author of the study and a joint PhD student at KTH and Bernstein Center Freiburg, Germany.
Kumar says the model, which he developed and tested with colleagues at the Bernstein Center Freiburg, at the University of Freiburg, Germany, sheds new light on cognitive problems associated with basal ganglia dysfunction, such as Parkinson’s disease and Tourette’s syndrome.
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Is it possible to tap into the signalling in the brain to figure out where you will go next? Hiroshi Ito, a researcher at the Kavli Institute for Systems Neuroscience at the Norwegian University of Science and Technology (NTNU), can now say yes. Ito has just published a description of how this happens in this week’s edition ofNature.
Ito and his colleagues, including his supervisors, 2014 Nobel Laureates May-Britt and Edvard Moser, sampled a specific neural pathway to figure out if it is the location of the mechanism that enables animals to code their plan to get from one place to another. Their study confirms that this pathway, the medial prefrontal cortex via a thalamic nucleus to the hippocampus, does.
The code that predicts behaviour
The researchers designed a study that would help them better understand how this signalling pathway works. They trained rats to run in an alternating fashion in a continuous T-maze that actually looks more like the infinity sign with a wide waist, or stem.
“We learned that the differential strength of firing of specific neurons accurately predicts the trajectory the animal will chose,” Ito said.
While the rats ran the maze, electrophysiological recordings were made from prefrontal cortex, thalamus and hippocampus. The researchers analysed the activity of neurons while the rat was on the stem of the maze, where it had to decide whether to go left or right at the upcoming junction.
The decision pathway
Researchers know there are pathways from the prefrontal cortex via the thalamus to the CA1 area of the hippocampus. However, there is no link to the CA3 area immediately adjacent to CA1 (which is also in the hippocampus). Given this, the researchers first checked to see if they could detect a difference in the coding between the two areas that would reflect the trajectory the rat would subsequently choose. There was a clear difference. The CA1 showed far more coding for any upcoming choice than the CA3.
The code was visible in the intensity of firing, although not in which cell fired, or where. To understand how this works, think of a choir all singing the same song, but where different voices are louder at the same point in the song during different performances. The words, melody, and singers are the same, but the change in the volume of each voice changes the performance. Since they are familiar with “the choir”, the researchers looked for the conductor, which they found in the frontal cortex.
Researchers have known that the code for trajectory choice could be found in CA1. The researchers at the Kavli Institute showed that a similar code is present in nucleus reuniens (NR) in the thalamus as well as anterior cingulate (AC) and prelimbic cortex (PC), both in the medial prefrontal cortex (mPFC). The researchers continued to find out where the signals arise, and tested the contribution of the mPFC-NR pathway. The researchers were able to establish that without the input from mPFC through NR, the CA1 also loses its code for upcoming choice of trajectory. They were able to confirm this by blocking signalling in the NR, using two different approaches. This shows that the code needs mPFC and NR, much like a choir needs its conductor.
“Planning our movement to a desired location requires more than a map of where we are,” Professor May-Britt Moser says. “We must have a sense of both where we are at the moment, and where we want to go at the same time. It seems that the cells involved in navigation use both internal and external clues to pinpoint exact locations, and on top of the firing pattern there is a code of differential firing intensity that contains information on the next move.”
Moser explains that this intensity pattern appears to be under the guidance of the prefrontal cortex, a brain area known in primates for decision making and executive function.
“We believe these findings collectively suggest that the new pathway in charge of intended movement is crucial for animals to choose their actions to a desired place in a map,” Moser said. “The data also provide evidence for a role of the thalamus in long-range communication between cortical regions.”
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