Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.28.314526v1?rss=1 Authors: Blumenstock, S., Sun, F., Marinkovic, P., Sgobio, C., Liebscher, S., Herms, J. Abstract: Alpha-synucleinopathies are characterized by self-aggregation of the protein alpha-synuclein (a-syn), causing alterations on the molecular and cellular level. To unravel the impact of trans-neuronal spreading and templated misfolding of a-syn on the microcircuitry of remotely connected brain areas, we investigated cortical neuron function in awake mice 9 months after a single intrastriatal injection of a-syn preformed fibrils (PFFs), using in vivo two-photon calcium imaging. We found altered function of layer 2/3 cortical neurons in somatosensory cortex (S1) of PFF-inoculated mice, as witnessed by an enhanced response to whisking and increased synchrony, accompanied by a decrease in baseline Ca2+ levels. Stereological analyses revealed a reduction in GAD67-positive inhibitory cells in S1 in PFF-injected brains. These findings point to an impaired excitation/inhibition balance as an important pathomechanism in alpha-synucleinopathies and demonstrate a clear association between the spread of toxic proteins and the initiation of altered neuronal function in remotely connected areas. Copy rights belong to original authors. Visit the link for more info