Organization of basal ganglia circuits

Anatomical regions and how we define boundaries between and within structures in the brain put a constraint on our understanding of the brain. More than a century of research on the brain has revealed its fundamental organization to be based on single nerve cells communicating through electrical signals over chemical synapses. The fundamental organization on higher levels than circuits has been harder to unravel and often left to intuitive definitions based on immediate visual appearances like cell density or other cytoarchitectural criteria. In this thesis, I've developed an anatomical method where the entire mouse brain is reconstructed from tissue sections. This method combined with a genetic strategy for retrograde transsynaptic labeling of genetically-defined populations lets us tease apart the connectivity in an interconnected set of subcortical nuclei known as the basal ganglia. The method can further be extended across a large number of cell types to find generic patterns of connectivity across the entire brain. Lastly, the method enables us to utilize recent advances in mRNA sequencing to resolve the entire transcriptome of a single brain. The method, therefore, enables investigators to map out the fundamental organization of the brain both in terms of gene expression and connectivity, thereby providing a novel way to redefine neuroanatomy.

List of scientific papers

I. Pollak Dorocic, I., Fürth, D., Xuan, Y., Johansson, Y., Pozzi, L., Silberberg, G., Carlén, M., and Meletis, K. A Whole-Brain Atlas of Inputs to Serotonergic Neurons of the Dorsal and Median Raphe Nuclei. Neuron. 2014;83:663-678.
https://doi.org/10.1016/j.neuron.2014.07.002

II. Fürth, D., Vaissière, T., Ourania, T., Xuan, Y., Märtin, A., Lazaridis, I., Spigolon, G., Fisone, G., Tomer, R., Deisseroth, K., Carlén, M., Miller, C., Rumbaugh, G., and Meletis, K. An interactive framework for whole-brain maps at cellular resolution. [Accepted]
https://doi.org/10.1038/s41593-017-0027-7

III. Fürth, D., Ourania, T., Xuan, Y., Yoo, E., Lazaridis, I., Carlén, M., and Meletis, K. A monosynaptic scalable architecture revealed by whole-brain transsynaptic rabies tracing. [Manuscript]

IV. Fürth, D., Märtin, A., Navarro, J.F., Jurek, A., Frisén, J., Lundeberg, J., and Meletis, K. Atlas of the spatial transcriptome in adult mouse brain. [Manuscript]