Scientists are one step closer to understanding how the part of our brain central for decision-making and the development of addiction is organized on a molecular level. Researchers at Karolinska Institutet, in mouse models and with methods used for mapping cell types and brain tissue, were able to visualize the organization of different opioid-islands in the striatum.

“Our map forms the basis for a new understanding of the brain’s probably most important network for decision-making. It may contribute to an increased understanding of both normal reward processes and the effects of various addictive substances on this network,“

says the main author Konstantinos Meletis, associate professor at the Department of Neuroscience at Karolinska Institutet.

Spatiomolecular Code

Researchers created a molecular 3-D-map of the nerve cells targeted by opioids, such as morphine and heroin, and showed how they are organized in the striatum[1]. It is an important step toward understanding how the brain’s network governing motivation and drug addiction is organized. They describe a spatiomolecular code that can be used to divide striatum into different subregions.

[caption id="attachment_101917” align="aligncenter” width="700”]striatum map Credit: Antje Märtin, et al. CC-BY[/caption]

To find this molecular code, the researchers used single-nucleus RNA sequencing, a method to study small differences in individual cells, and mapping of the striatal gene expression. The results provide the first demonstration of molecular codes that divide the striatum into three main levels of classification: a spatial, a patch-matrix and a cell-type specific organization.

“With this new knowledge we may now begin to analyze the function of different types of nerve cells in different molecularly defined areas,” says Meletis. “This is the first step in directly defining the networks’ role in controlling decision-making and addiction with the help of optogenetics.“

This new knowledge may also form the basis for the development of new treatments based on a mechanistic understanding of the brain’s network, according to the researchers:

“A number of interesting questions remain regarding the spatiomolecular codes: do these represent discrete connectivity profiles, or some specific signaling pathways, and are these established during development? And are there mechanisms to maintain those signals in the adult? Ultimately, it will be important to understand the functional properties of the proteins that generate the spatial code.

Neuroanatomical models have been central to developing theories on the function of neuronal circuits, and it is therefore important to establish systematic maps that integrate information on the position, identity, and connectivity of neurons. Increasing knowledge on the diversity of neuron types and how molecular information can be used to map cells and tissue in a common reference framework will guide efforts to map function onto the circuit structure,“

they conclude.

[1] Antje Märtin, Daniela Calvigioni, Ourania Tzortzi, Janos Fuzik, Emil Wärnberg, Konstantinos Meletis. A Spatiomolecular Map of the Striatum. Cell Reports; Volume 29, Issue 13, p4320-4333.E5, December 24, 2019

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