Sensing neuronal activity in transplanted cortical organoids
Cortical organoids are rapidly advancing as models of human brain development and disease and offer promise as neural prosthetics to restore lost or degenerated brain regions. However, due to limitations in longitudinal recording technologies, organoids’ beneficial abilities to functionally connect with host cortex upon implantation and respond to external sensory stimulation have yet to be demonstrated. In our new study in collaboration with the Kuzum and Muotri labs at UCSD, we established a novel paradigm combining transparent graphene electrode arrays and two-photon microscopy for longitudinal, multimodal monitoring of organoids implanted in mice cortices. Over the course of eleven weeks, we recorded local field potentials and multi-unit activity (MUA) from organoids in response to visual stimulation and during spontaneous activity. Examining the electrophysiological responses to visual stimulation, we found that the evoked responses in organoids matched that of the surrounding cortex, suggesting functional connectivity had formed between organoids and mouse tissue. In further support of functional connectivity, we observed increases in gamma and MUA power and phase locking of MUA to local field potentials following visual stimulation. Two-photon microscopy confirmed functional vascularization of the organoids. Using post-mortem immunohistochemistry, we observed synaptic connectivity and morphological fusion between organoids and host mouse cortices. Our novel, multimodal recording setup revealed the first demonstration of organoids functionally connecting to mouse visual cortical networks and offers a unique platform through which researchers can study the potential of organoids to restore damaged brain regions upon integration.
|Meet first co-author
|Meet first co-author
Dr. Martin Thunemann
|Multimodal monitoring of human cortical organoids implanted in mice using transparent graphene microelectrodes reveal functional connection between organoid and mouse visual cortex
Madison N. Wilson, Martin Thunemann, et al.