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De Vos, W. H.

Publications and source records attributed to De Vos, W. H..

2 recordsLinked to original sources

Chemogenetic silencing of neurons in the mouse anterior cingulate area modulates neuronal activity and functional connectivity

The anterior cingulate area (ACA) is an integral part of the prefrontal cortex in mice and has been implicated in several cognitive functions. Previous anatomical and functional imaging studies demonstrated that the ACA is highly interconnected with numerous brain regions acting as a hub region in functional networks. However, the importance of the ACA in regulating functional network activity and connectivity remains to be elucidated. Recently developed neuromodulatory techniques, such as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) allow for precise control of neuronal activity. In this study, we used an inhibitory kappa-opioid receptor DREADDs (KORD) to temporally inhibit neuronal firing in the right ACA of mice and assessed functional network activity and connectivity using non-invasive functional MRI. We demonstrated that KORD-induced inhibition of the right ACA induced blood oxygenation-level dependent (BOLD) signal decreases and increases in connected brain regions throughout of hemispheres. Furthermore, these modulations in neuronal activity were associated with decreased intra- and interhemispheric functional connectivity. These results demonstrate that the combination of the DREADD technology and non-invasive functional imaging methods is a valuable tool for unraveling the underlying mechanisms of network function and dysfunction.

neuroscience

Deep coverage microscopy exposes a pharmacological window for modifiers of neuronal network connectivity

BackgroundTherapeutic developments for neurodegenerative disorders are redirecting their focus to the mechanisms that contribute to synaptic plasticity and the loss thereof. Identification of novel regulators requires a method to quantify neuronal network connectivity with high accuracy and throughput. To meet this demand, we have established a microscopy-based pipeline that integrates morphological and functional correlates of connectivity in primary neuronal culture. ResultsWe unveiled a connectivity signature that was specific to the cell type and culture age. We defined a score that accurately reports on the degree of neuronal connectivity and we validated this score by targeted perturbation of microtubule stability and selective depletion of anti-oxidants. With a focused compound screen, we discovered that inhibition of dual leucine zipper kinase activity increased neuronal connectivity in otherwise unperturbed cultures and exerted neuroprotective effects in cultures grown under sub-optimal or challenged conditions. ConclusionsOur results illustrate that profiling microscopy images with deep coverage enables sensitive interrogation of neuronal connectivity and allows exposing a dose and time window for pharmacological interventions. Therefore, the current approach holds promise for identifying pathways and compounds that preserve or rescue neuronal connectivity in neurodegenerative disorders.

neuroscience