Colloquium: Internally generated sequential firing patterns in human brain organoids

19 January 2023

Colloquium by Prof. Dr. Tal Sharf, Dept Biomolecular Engineering, University of California Santa Cruz

Abstract: Human brain organoids represent a self-organized neuronal system that replicates key facets of cellular diversity, developmental anatomy and functional connectivity found in in vivo brain networks (Sharf et al. 2022). An ongoing conjecture in neuroscience is that cognition depends on self-generated sequential activation of neuronal assemblies within the brain (Pastalkova et al. 2008). Brain organoids provide an experimental framework to investigate intrinsic temporal dynamics within hierarchically organized neuronal assemblies, composed of both excitatory and inhibitory networked neurons, that emerge devoid of an external input.

Utilizing high-density CMOS microelectrode arrays containing 26,400 recording sites, we measured extracellular action potentials generated by spontaneous spiking activity across the surface of a human brain organoid. From tracking the transient dynamics of single-unit firing rates we identified ensembles of neurons that initiate, align and disperse within a time course of a few hundred milliseconds. Utilizing these readouts of neuronal activity, we found neuronal ensembles with reliable, sequentially activated spike patterns that form temporally aligned sequences. A subset of these neurons exhibit a sharp increase in temporal alignment with respect to peak activity within neuronal population bursts and form stable ensemble trajectories. Surprisingly, temporal dynamics generated by our brain organoids resemble temporal signatures of firing patterns observed in neuronal assemblies in vivo. These assemblies have been hypothesized to function as computational units, and are retained and activated during sleep when largely disengaged from external inputs (Peyrache et al. 2015). These results suggest that perturbation of intrinsically self-organized neuronal patterns with electrical and/or optogenetic stimulation may open a new paradigm for encoding and reading information delivered from an external input to a human brain organoid.

Further information about the speakers can be found sharflab.ucsc.edu.

The talk is part of the SFB 936 Methods Academy and will be streamed live via Zoom:
Contact the SFB secretariat to get access.

Date and time: Thursday, 19.01.2023 17:00-18:30 Zoom lecture