Slow brain oscillations: from dendritic spines to large-scale circuits

Arthur Konnerth

Institute of Neuroscience, Technical University Munich, Germany

Cortico-thalamic slow oscillations determine internal brain states, playing a major role in memory consolidation. Such oscillations occur spontaneously, but may also be evoked by sensory stimulation. Here we implemented an optogenetic approach to explore basic features of slow-oscillation generation and propagation in the in vivo mouse brain. The temporal invariance and the globality of the Ca2+ waves suggest the presence of recurring large-scale neuronal 'signaling units' during which activity generated by local networks is distributed and processed throughout the cortex. We demonstrate that slow-wave activity is severely altered in the neocortex, thalamus and hippocampus in mouse models of Alzheimer Disease amyloidosis. Most notably, our results reveal an Abeta-dependent impairment of slow-wave propagation, which causes a breakdown of the characteristic long-range coherence of slow-wave activity. The finding that the impairment can be rescued by enhancing GABAAergic inhibition identifies a synaptic mechanism underlying Abeta-dependent large-scale circuit dysfunction.