Expansion microscopy exposes brain connections
Well connected: expansion microscopy sheds light on neural networks and decision making.
Using expansion microscopy, MIT neuroscientists have discovered connections deep within the brain that appear to form a communication pathway between areas that control emotion, decision-making, and movement.
Professor Ann Graybiel from the McGovern Institute for Brain Research at MIT and colleagues suspect that these connections - striosome-dendron bouquets - may be involved in controlling how the brain makes decisions that are influenced by emotion or anxiety.
According to Graybiel, expansion microscope was crucial to the latest discovery.
Pioneered by Professor Ed Boyden from MIT Media Lab, the method is used to image large biological specimens at nanoscale resolution using, for example, a confocal microscope.
An expandable polymer and water swell tissue to around four and a half times its usual size, so that nanoscale structures, once blurry, appear within focus.
As part of the latest study, Graybiel and colleagues focused on a small region of the brain known as the striatum, which is part of the basal ganglia; a cluster of brain centres associated with habit formation, control of voluntary movement, emotion, and addiction.
Graybiel in her lab with research scientist Jill Crittenden. [Justin Knight]
Much of the striatum is uncharted territory, but Graybiel’s lab has previously located clusters of cells here known as striosomes that receive specific input from parts of the brain’s prefrontal cortex involved in processing emotions.
The team's studies have also suggested that striosomes relay information to cells within a region called the substantia nigra, one of the brain’s main dopamine-producing centres.
To investigate communication between these brain regions, Graybiel used expansion microscopy to image the striosomes and discovered extensive connections between those clusters of cells and dopamine-producing cells of the substantia nigra.
The dopamine-producing cells send down many dendrites that become entwined with axons that come up to meet them from the striosomes, forming a bouquet-like structure.
“With expansion microscopy, we could finally see direct connections between these cells by unraveling these unusual rope-like bundles of axons and dendrites,” highlights Graybiel’s colleague Jill Crittenden, a research scientist at the McGovern Institute.
“What’s really exciting to us is we can see that it’s small discrete clusters of dopamine cells with bundles that are being targeted,” she adds.
Connections between dopamine-producing cells of the substantia nigra (red) and neurons in the striatum (green); the connections, in yellow, may play a role in the brain’s decision-making processes.
The researchers reckon the striosomes may be acting as a gatekeeper that absorbs sensory and emotional information coming from the cortex and integrates it to produce a decision on how to react, which is initiated by the dopamine-producing cells, the researchers say.
Graybiel and colleagues now intend to extend studies to mice, and will selectively activate or shut down the striosome-dendron bouquet as the mice are prompted to make decisions.
They will also investigate whether these connections are disrupted in mouse models of Parkinson’s disease.
Malfunctions of the basal ganglia have been associated with Parkinson’s and Huntington’s diseases, as well as autism, obsessive-compulsive disorder, and Tourette’s syndrome, and Graybiel believes that this brain circuit could be a target of the neural degeneration seen in Parkinson’s disease.
Research is published in Proceedings of the National Academy of Sciences.