Mapping brain circuits : anatomy, connectivity and function

To decipher neural circuits anatomy is the central basis for all kinds of neurobiological studies. Here in this thesis, I will start with extensive overview of the current methods that have been intensively employed in labeling and mapping neurons and neuronal activities, including tracing techniques, imaging/recording systems and manipulation tools. This will be followed by the introduction of the two model systems that are being studied in this thesis.

Specifically, the ultimate goal of this thesis is to examine the anatomical neural circuits of involving median prefrontal cortex and the serotonergic nuclei, by developing a standardized brain atlas for automatic processing and analyzing anatomical image data, which facilitate functional studies of the serotonergic neurons in rats.

In paper I, we characterized the inputs to two major serotonergic nuclei using a retrograde trans-synaptic virus. We reconstructed a whole brain input map with customized software, and found previously undefined inputs. We also confirmed the existence of the functional connection from basal ganglia, lateral habenula, and prefrontal cortex to the raphe nuclei serotonergic neurons. In paper II, we developed a versatile interactive framework for automatic detection, registration, and analysis. In paper III, we characterized both the local and long-range inputs to four cell types in the mouse medial prefrontal cortex. A new viral strategy for tracing both local and long-range inputs at the same time was developed. We have confirmed the findings by other tracing techniques, and rebuilt our own connectivity map. In paper IV, we explored the roles of serotonergic neurons in impulsive behavior by manipulating and recording the neurons.

In summary, we have developed new methods for neural circuitry study, added our knowledge of the serotonergic and median prefrontal cortex circuitry, and gained deeper insights of functional roles of serotonergic neurons.

List of scientific papers

I. Iskra Pollak Dorocic, Daniel Fürth, YANG XUAN, Yvonne Johansson, Laura Pozzi, Gilad Silberberg, Marie Carlén, Konstantinos Meletis. A whole-brain atlas of inputs to serotonergic neurons of the dorsal and median raphe nuclei. Neuron. 2014, Volume 83, Issue 3, 663-678.
https://doi.org/10.1016/j.neuron.2014.07.002

II. Daniel Fürth, Thomas Vaissière, Ourania Tzortzi, YANG XUAN, Antje Märtin, Iakovos Lazaridis, Giada Spigolon, Gilberto Fisone, Raju Tomer, Karl Deisseroth, Marie Carlén, Courtney A. Miller, Gavin Rumbaugh & Konstantinos Meletis. An interactive framework for whole-brain maps at cellular resolution. Nature Neuroscience. 2018, 21, 139–149.
https://doi.org/10.1038/s41593-017-0027-7

III. YANG XUAN, Sofie Ährlund-Richter, Hoseok Kim, Iskra Pollak Dorocic, Felix Wahl, Konstantinos Meletis, Marie Carlén. [Manuscript]

IV. Xinming Wang, YANG XUAN, Hoseok Kim, Iskra Pollak Dorocic, Daniel Kaping, Marc Parent, Konstantinos Meletis, Marie Carlén. [Manuscript]