Summary: Researchers have discovered two new brain pathways that modify movement and emotional decisions by controlling the release of dopamine. These pathways, found in the striatum, stimulate or inhibit dopamine-producing neurons and influence the go and no-go pathways that control movement.
By modulating dopamine, these pathways may be particularly involved in decision-making related to strong emotions and anxiety. The findings provide new insights into how motivation and exercise are linked, with potential implications for diseases such as Parkinson’s disease.
Important facts:
Two newly identified brain pathways control dopamine release and influence movement. These pathways control decisions that involve strong emotions and anxiety. The findings may help understand movement-related diseases such as Parkinson’s disease.
Source: MIT
In the human brain, movement is coordinated by a brain region called the striatum, which sends instructions to motor neurons in the brain. These instructions are conveyed by two pathways: one that initiates movement (“go”) and one that inhibits it (“no-go”).
In a new study, MIT researchers discovered two additional pathways that occur in the striatum and appear to modulate the effects of the go and no-go pathways. These newly discovered pathways are connected to dopamine-producing neurons in the brain, with one stimulating the release of dopamine and the other suppressing it.
These pathways appear to modify the instructions given by the go and no-go pathways by controlling the amount of dopamine in the brain via clusters of neurons known as striosomes. Emotional factors in particular can strongly influence decision-making, the researchers said.
“Of all the regions of the striatum, we found that only striosomes can project to dopamine-containing neurons, which are thought to be involved in the control of motivation, mood, and movement,” MIT Institute says Anne Graybeal. Professor, member of the McGovern Institute for Brain Research at the Massachusetts Institute of Technology, and senior author of the new study.
Iakovos Lazaridis, a researcher at the McGovern Institute, is the lead author of the paper, which is published today in the journal Current Biology.
new route
Graybeal has spent much of his career studying the striatum. The striatum is a structure located deep in the brain that is involved in learning, decision-making, and motor control.
Within the striatum, neurons are arranged in a maze-like structure containing striosomes, which Graybeal discovered in the 1970s. The classical go and no-go pathways arise from neurons surrounding striosomes, collectively known as the matrix.
The stromal cells that give rise to these pathways receive input from sensory processing areas such as the visual and auditory cortices. It then sends go or no-go commands to neurons in the motor cortex.
However, the function of striosomes, which are not part of these pathways, remained unclear. For years, researchers in Graybeal’s lab have been trying to solve the mystery.
Their previous research revealed that striosomes receive much of their input from parts of the brain that process emotions. There are two main types of neurons within the strisome, classified as D1 and D2. In a 2015 study, Graybeal discovered that one of these cell types, D1, sends input to the substantia nigra, the brain’s main dopamine-producing center.
Tracing the output of the other set, D2 neurons, took much longer. In a new Current Biology study, researchers found that these neurons also ultimately project to the substantia nigra, but initially connect to a series of neurons in the optic bulb that inhibit dopamine output. . This pathway is an indirect connection to the substantia nigra, which reduces the brain’s dopamine output and inhibits movement.
The researchers also confirmed previous findings that a pathway originating from the D1 striosome connects directly to the substantia nigra and stimulates dopamine release to initiate movement.
“We found something in the striosome that probably mimics the classical go/no-go pathway,” Graybeal says.
“They’re similar to the classic go-no-go pathway of movement, but they don’t go to motor output neurons in the basal ganglia. Instead, they go to dopamine cells, which are so important for movement and motivation.”
emotional decision
This finding suggests that classical models of how the striatum controls movement need to be revised to incorporate the role of these newly identified pathways. The researchers now want to test the hypothesis that motivational and emotion-related inputs from the cortex and limbic system into the striosome influence dopamine levels in ways that promote or inhibit behavior. are.
Dopamine release may be particularly relevant to anxiety- and stress-inducing behaviors. In a 2015 study, Graybeal’s lab found that striosomes play an important role in decision-making that causes high levels of anxiety. In particular, although the risks are high, the rewards can also be high.
“Anne Graybeal and colleagues previously discovered that striosomes are involved in inhibiting dopamine neurons. Now they show that another type of striosome neuron exerts the opposite effect, signaling reward. Therefore, we unexpectedly showed that striosomes can upregulate or downregulate dopamine activity, which is a very important finding.
“The regulation of dopamine activity is clearly important in our daily lives, both with regard to movement and mood, and striosomes are involved,” says Sten Grillner, professor of neuroscience at Sweden’s Karolinska Institutet. . the study.
Another possibility the researchers plan to investigate is whether striosomes and matrix cells are arranged in modules that influence motor control in specific parts of the body.
“The next step is to isolate some of these modules and simultaneously manipulate cells that belong to the same module, whether it’s in the matrix or in the striosome, so that the striosome is at the root of each of these modules. “It’s about trying to pinpoint how to regulate these functions,” Lazaridis says.
They also want to investigate how striosomal circuits, which project to the same areas of the brain that are disrupted by Parkinson’s disease, influence the disorder.
Funding: This research was supported by the National Institutes of Health, the Sachs-Kavanaugh Foundation, the William N. and Bernice E. Bumpass Foundation, Jim and Joan Schattinger, and the Hock E. Tan and K. Lisa Yang Center for Autism Research. , Robert Buxton, Simmons Foundation, CHDI Foundation, Ellen Shapiro and Gerald Axelbaum BBRF Young Investigator Grant.
About this dopamine and neuroscience research news
Author: Ann Trafton
Source: MIT
Contact: Ann Trafton – MIT
Image: Image credited to Neuroscience News
Original research: Open access.
“Striosomes control dopamine through a dual pathway that parallels the canonical basal ganglia circuit” by Iakovos Lazaridis et al. Current Biology
abstract
Striosomes control dopamine through a dual pathway that parallels canonical basal ganglia circuits
Balanced activity of the canonical direct D1 and indirect D2 basal ganglia pathways is considered a core requirement for normal movement, and their imbalance is the pathogenesis of motor and neuropsychiatric disorders.
We present evidence for a conceptually equivalent pair of direct D1 and indirect D2 pathways that arise from striatal projection neurons (SPNs) in the striosomal compartment rather than from SPNs in the matrix as in the canonical pathway.
These striosome D1 (S-D1) and D2 (S-D2) pathways target substantia nigra dopamine-containing neurons rather than basal ganglia motor output nuclei. They modulate movement with a net effect opposite to that exerted by the canonical pathway. S-D1 is net inhibitory and S-D2 is net excitatory.
S-D1 and S-D2 circuits influence learning and behavioral motivation, and can complement and redirect canonical pathway regulation.
A major conceptual reformulation of the classic direct-indirect pathway model of basal ganglia function is needed, as is a reexamination of the effects of D2-targeted therapeutics.
