Munich Cluster for Systems Neurology
print


Breadcrumb Navigation


Content

Cortical circuit dysfunction in a mouse model of alpha-synucleinopathy in vivo.

Brain Commun. 2021 Nov 15;3(4):fcab273. doi: 10.1093/braincomms/fcab273. PMID: 34877534; PMCID: PMC8643497.

Authors/Editors: Blumenstock S, Sun F, Klaus C, Marinković P, Sgobio C, Paeger L, Liebscher S, Herms J.
Publication Date: 2021

Abstract

Considerable fluctuations in cognitive performance and eventual dementia are an important characteristic of alpha-synucleinopa-thies, such as Parkinson’s disease and Lewy Body dementia and are linked to cortical dysfunction. The presence of misfolded and aggregated alpha-synuclein in the cerebral cortex of patients has been suggested to play a crucial role in this process. However, the consequences of a-synuclein accumulation on the function of cortical networks at cellular resolution in vivo are largely unknown. Here, we induced robust a-synuclein pathology in the cerebral cortex using the striatal seeding model in wild-type mice. Nine months after a single intrastriatal injection of a-synuclein preformed fibrils, we observed profound alterations of the function of layer 2/3 cortical neurons in somatosensory cortex by in vivo two-photon calcium imaging in awake mice. We detected increased
spontaneous activity levels, an enhanced response to whisking and increased synchrony. Stereological analyses revealed a reduction in glutamic acid decarboxylase 67-positive inhibitory neurons in the somatosensory cortex of mice injected with preformed fibrils. Importantly, these findings point to a disturbed excitation/inhibition balance as a relevant driver of circuit dysfunction, potentially underlying cognitive changes in alpha-synucleinopathies.

 

01-blumenstock

Related Links