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Knöpfel, T.

Publications and source records attributed to Knöpfel, T..

4 recordsLinked to original sources

Hippocampal gamma and sharp wave/ripples mediate bidirectional interactions with cortical networks during sleep

Hippocampus-neocortex interactions during sleep are critical for memory processes: hippocampally-initiated replay contributes to memory consolidation in the neocortex and hippocampal sharp wave/ripples are linked to generalized increases in neocortical cell activity and DOWN-UP state transitions. Yet, the spatial and temporal patterns of this exchange are unknown. With voltage imaging, electrocorticography, and laminarly-resolved hippocampal potentials, we characterized cortico-hippocampal interactions during anesthesia and NREM sleep. We observed neocortical activation transients spanning multiple spatial scales hinting at a quasi-critical regime. Transients were organized in a small number of functional networks matching known anatomical connectivity. A network overlapping with the default mode network and centered on retrosplenial cortex was the most associated with the hippocampus. Interestingly, hippocampal slow gamma was the oscillation that best correlated with this neocortical network, outpacing ripples. In fact, neocortical activity predicted hippocampal slow gamma and followed ripples, suggesting that consolidation processes rely on bi-directional exchanges between hippocampus and neocortex.

neuroscience↗

Inhibition is a prevalent mode of activity in the neocortex around awake hippocampal ripples

Coordinated peri-ripple activity in the hippocampal-neocortical network is essential for mnemonic information processing in the brain. Hippocampal ripples likely serve different functions in sleep and awake states. Thus, the corresponding neocortical activity patterns may differ in important ways. We addressed this possibility by conducting voltage and glutamate wide-field imaging of the neocortex with concurrent hippocampal electrophysiology in awake mice. Contrary to our previously published sleep results, deactivation and activation were dominant in post-ripple neocortical voltage and glutamate activity, respectively, especially in the agranular retrosplenial cortex (aRSC). Additionally, the spiking activity of aRSC neurons, estimated by two-photon calcium imaging, revealed the existence of two subpopulations of excitatory neurons with opposite peri-ripple modulation patterns: one increases and the other decreases firing rate. These differences in peri-ripple spatiotemporal patterns of neocortical activity in sleep versus awake states might underlie the reported differences in the function of sleep versus awake ripples.

neuroscience↗

Psilocybin rescues sociability deficits in an animal model of autism

Autism spectrum disorder (ASD) is characterized by core deficits in social interaction. The classic serotonergic psychedelic psilocybin has been suggested as a therapeutic agent that may ameliorate in the core symptomology of ASD. We found that the acute response to psilocybin was attenuated in the prenatal valproic acid exposure mouse model of ASD, and importantly, psilocybin rescued the social behavioural abnormalities present in these ASD model mice.

neuroscience↗

Subcellular resolution 3D light field imaging with genetically encoded voltage indicators

Light field microscopy (LFM) enables high signal-to-noise ratio (SNR), light efficient volume imaging at fast frame rates, and has been successfully applied to single-cell resolution functional neuronal calcium imaging. Voltage imaging with genetically encoded voltage indicators (GEVIs) stands to particularly benefit from light field microscopys volumetric imaging capability due to high required sampling rates, and limited probe brightness and functional sensitivity. Previous LFM studies have imaged GEVIs to track population-level interactions only in invertebrate preparations and without single cell resolution. Here we demonstrate sub-cellular resolution GEVI light field imaging in acute mouse brain slices resolving dendritic voltage signals localized in three dimensions. We characterize the effects of different light field reconstruction techniques on the SNR and signal localization and compare the SNR to fluorescence transients imaged in wide field. Our results demonstrate the potential of light field voltage imaging for studying dendritic integration and action potential propagation and backpropagation in 3 spatial dimensions.

neuroscience↗