Issue 39, 2024

In vivo photopharmacological inhibition of hippocampal activity via multimodal probes – perspective and opening steps on experimental and computational challenges

Abstract

Neurological conditions such as epilepsy can have a significant impact on people's lives. Here, we discuss a new perspective for the study/treatment of these conditions using photopharmacology. A multimodal, intracranial implant that incorporates fluidic channels for localised drug delivery, electrodes for recording and stimulation, and a light source for photoswitching is used for in vivo administration and deactivation of a photoresponsive AMPA antagonist. We review current advancements in the relevant disciplines and show experimentally that the inhibition of seizure-like events induced in the hippocampus by electrical stimulation can be altered upon switching the drug with light. We discuss the interconnection of the drug's photopharmacological properties with the design of the device by modelling light penetration into the rat brain with Monte Carlo simulations. This work delivers a new perspective, including initial experimental and computational efforts on in vivo photopharmacology to understand and eventually treat neurological conditions.

Graphical abstract: In vivo photopharmacological inhibition of hippocampal activity via multimodal probes – perspective and opening steps on experimental and computational challenges

Supplementary files

Article information

Article type
Perspective
Submitted
23 May 2024
Accepted
14 Aug 2024
First published
15 Aug 2024
This article is Open Access
Creative Commons BY license

J. Mater. Chem. B, 2024,12, 9894-9904

In vivo photopharmacological inhibition of hippocampal activity via multimodal probes – perspective and opening steps on experimental and computational challenges

J. Gurke, A. Carnicer-Lombarte, T. E. Naegele, A. K. Hansen and G. G. Malliaras, J. Mater. Chem. B, 2024, 12, 9894 DOI: 10.1039/D4TB01117A

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