The Research Group Molecular Imaging and Optogenetics focuses on combining state-of-the-art optogenetic techniques with optical neuroimaging.
The research group Stroh strives at investigating the interrelation of spontaneous and sensory-evoked activity of single neurons, and neuronal ensembles, on the (dysregulated) functional halamo-cortical network in rodents, both under physiological and pathophysiological conditions. For that, we implement all optical and optomagnetic multi-modal approaches, such as 2-photon Ca2+ imaging, optic-fiber-based Ca2+ recordings, single cell optogenetics, and functional MRI. Using an optic-fiber-based recording method, we conducted a causal in vivo study aimed at probing the initiation of thalamo-cortical slow-oscillations-associated Ca2+ waves (Stroh et al., 2013, Neuron
). We could demonstrate that brief stimulation of a local group of layer 5 cortical neurons is sufficient for the induction of cortex-wide slow-oscillations. Just recently, we combined these optical recordings of slow oscillations with simultaneous fMRI, to attain the brain-wide fMRI signature of slow oscillations. The individual slow wave events were used for an event-related analysis of simultaneously acquired whole-brain BOLD fMRI. We identified BOLD responses directly related to onsets of slow calcium waves, revealing a cortex-wide BOLD correlate: the entire cortex was engaged in this specific type of slow wave activity (Schwalm et al., eLife 2017
On the level of cortical microcircuits, we recently causally explored the role of parvalbumin-expressing interneurons on cortical processing of sensory-evoked afferents in mouse barrel cortex in vivo. Optogenetic inhibition of PV interneurons led to a broad-spectrum power increase both in spontaneous and sensory-evoked activity. Whisker-evoked responses were significantly increased after stimulus onset during inhibition of PV interneurons, demonstrating high temporal precision of PV-shaped inhibition. Multi-unit activity was strongly enhanced in neighboring cortical columns, but not at the site of transduction, supporting a central and highly specific role of PV interneurons in lateral inhibition. Histological assessment of transduced cells combined with quantitative modeling of light distribution and spike sorting revealed that only a minor fraction (~10%) of the local PV population comprising no more than a few hundred neurons is optogenetically modulated, mediating the observed prominent and wide-spread effects on neocortical processing (Yang et al. 2017, Cereb. Cort
Teaming up with clinical scientists, we employed network centered approaches in early-stage models of neurological disorders, aiming at defining the network as own pathophysiological entity. Indeed, neurological disorders as diverse as multiple sclerosis (MS), Alzheimer’s disease (AD), and Huntington´s disease (HD) are characterized by a functional impairment of neural circuits underlying cognitive and motor functions. Although demyelination and axonal damage or neuronal and synapse loss are central in the pathophysiology, only recently neuronal network dysfunctions, representing new allostatic set points on network level, have been proposed to have a significant contribution to disease burden. They may even represent a pathology in itself, only indirectly mediated by initial pathological insult. In AD and HD, for example these network disturbances occur already during the early stage of the disease, and in MS, such alterations may also explain functional disturbances during disease progression far beyond the initial immune attack to the brain. Indeed, we did already find aberrant network functionality in cortical areas unaffected by initial pathology in animal models of MS, AD, and HD (Ellwardt et al. Nature Neurosci. 2018, Arnoux et al. eLife 2018
On the topic of resilience research we aim at causally unravelling the neuronal underpinnings of resilient behavior in rodent models of resilience. We focus on primary cortical areas, as in our view, resilient behavior needs to affect already the basic computation of sensory afferences in the cortex. We investigate both local representation of sensory inputs in cortical microcircuits, as well as cortico-cortical integration and interpretation, in behaving rodents. This experimental setting allows for establishing a causality between spatio-temporal patterns of microcircuit activity and resilient versus susceptible behavior, with a focus on slow oscillations.