It Is Just a Matter of Cues: Multidimensional Modulation of Neuronal Network Activity Through Multimodal Stimulation
Faculty of Pharmacy [UPV/EHU] (Vitoria-Gasteiz, Spain)
25 Nov 2022 13:00
Aketxe Room, Sede building, Leioa
In the past decade, (nano)technology applications to the central nervous system have often involved studying and developing novel strategies to drive the formation of neuronal networks and modulate their electrical activity. Indeed, the ability to govern neuronal excitability could have a significant impact on fundamental neurophysiology and in establishing novel therapeutic approaches to treat neurological dysfunctions.
By exploiting 2D and 3D cultures of dissociated primary cells, we demonstrated that neuronal network activity could be altered by the synergic contribution of the physicochemical properties of the cell-interfacing surface, the topological network organization, and the environmental mechanical properties. Specifically, surface modification via carbon-based nanomaterials (CBNs) has been demonstrated to play a pivotal role in neuromodulation. By growing neuronal cells on 2D supports or within 3D scaffolds, we have demonstrated that graphene and carbon nanotubes surface modifications are fully biocompatible and able to induce in cultured neurons increased synaptic activity. We also highlighted the impact of the three-dimensional organization on the overall pattern of electrical activity. On the other hand, we investigated how environmental compliance impacts neuronal behavior, attempting to shed some light on the mechanism linking compliance-mediated mechanical and electrical adaptation. Our preliminary data showed that compliant substrates downregulate neuronal electrical activity through a cholesterol-mediated adaptive process.
From this evidence, we aim to develop an integrated multimodal approach to artificially recapitulate the different cues provided by the extra-cellular matrix (ECM) in orchestrating central nervous system development and functionality.