In Vivo Neurophysiology

We study how individual cortical neurons encode sensory stimuli and how sensory representation is affected by behavior. The rodent barrel cortex is an excellent system to study these questions since the individual sensory organs (facial whiskers) are represented by easily identifiable cortical columns. Additionally, our group is part of an international effort to understand human brain function at (sub)cellular resolution.

Research

Building blocks of the human brain

Very little is known about the cell-types and their properties in the human brain. The recently developed patchseq method allows a detailed characterization of gene transcription, morphology and biophysics on the single cell level (Berg et al, Nature 2021, Lee & Dalley, Science 2023, Chartrand et al, Science 2023). Here, we use human brain tissue obtained during resection surgery and apply the patchseq method to map the transcriptomic landscape of individual cell-types towards uncovering cellular diversity in the human brain. We use machine learning to study the causal link between cell-type identity, transcriptomic landscape, biophysical properties and morphology.

Sensory processing during behavioral paradigms

During animal behavior, there is a constant interplay between brain areas involved in sensory processing, decision making and motor output. The whisker system is an obvious example of a sensorimotor system where motor output (movement of the sensory organs (i.e. the whiskers)) has to be integrated with incoming sensory information. In turn, the sensorimotor information guides cognitive behaviour. Our research question focusses on the organisational principles of the cortical microcircuit across distinct areas of the sensorimotor system. Techniques used are behavioral training, (in vivo) electrophysiology in awake, behaving animals (including optogenetics) and post-hoc 3D Neurolucida reconstructions.

Sensory processing in prefrontal cortex

Sensory information typically consists of more than one modality (for instance: auditory + visual information). We aim to understand how multi-sensory integration is performed in primary sensory regions. Techniques used are behavioural training, (in vivo) single- and multi-unit electrophysiology in behaving animals and post-hoc histology.

3D reconstruction of labeled neurons

Computer models can be helpful tools to design and direct future experiments and predict possible outcomes. Using 3D reconstructions from in vivo recordings, the first goal is to anatomically reconstruct the cortical column. Then, physiological data will be used to model (and playback) the electrical activity of the cortical column. This project is a collaboration with Marcel Oberlaender and Bert Sakmann from the Max-Planck Institute of Neurobiology, Germany. Techniques used are 3D Neurolucida reconstructions and computer modeling of morphological and physiological properties.

Selected Publications

Mertens*, E.J., Leibner*, Y., et al, de Kock#, C.P.J., Morpho-electric diversity of human hippocampal CA1 pyramidal neurons. Cell Reports, 2024 Apr 11;43(4):114100. doi: 10.1016/j.celrep.2024.114100. Online ahead of print. PMID: 38607921

Lee, B.R., Dalley, R., …., Kalmbach, B., de Kock, C.P.J., Mansvelder, H.D., Sorensen, S.A., Tamas, G., Lein, E.S., Ting, J.T. Signature morphoelectric properties of diverse GABAergic interneurons in the human neocortex. Science. 2023 Oct 13;382(6667): eadf6484. doi: 10.1126/science.adf6484. Epub 2023 Oct 13.

Chartrand, T., Dalley, R., ….., de Kock, C.P.J., Mansvelder, H.D., Tamas, G., Zeng, H., Kalmbach, B., Lein, E.S. Morphoelectric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex. Science. 2023 Oct 13;382(6667): eadf0805. doi: 10.1126/science.adf0805. Epub 2023 Oct 13.

Hunt*, S., Leibner*, Y., de Kock, C.P.J., Strong and reliable synaptic communication between pyramidal neurons in adult human cerebral cortex, CerebCtx, 2023 Mar 10;33(6):2857-2878. doi: 10.1093/cercor/bhac246.

Berg*, J., Sorensen*, S., ….. , Segev, I., de Kock, C.P.J., Mansvelder, H.D., Tamas, G., Zeng, H., Koch, C., Lein, E.S., Human neocortical expansion involves glutamatergic neuron diversification. Nature. 2021 Oct;598(7879):151-158. doi: 10.1038/s41586-021-03813-8. Epub 2021 Oct 6.