Ex Vivo Feedback Control of Neurotransmission Using a Photocaged Adenosine A1 Receptor Agonist.

International journal of molecular sciences 2022 Aug 10

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We report the design, synthesis, and validation of the novel compound photocaged N6-cyclopentyladenosine (cCPA) to achieve precisely localized and timed release of the parent adenosine A1 receptor agonist CPA using 405 nm light. Gi protein-coupled A1 receptors (A1Rs) modulate neurotransmission via pre- and post-synaptic routes. The dynamics of the CPA-mediated effect on neurotransmission, characterized by fast activation and slow recovery, make it possible to implement a closed-loop control paradigm. The strength of neurotransmission is monitored as the amplitude of stimulus-evoked local field potentials. It is used for feedback control of light to release CPA. This system makes it possible to regulate neurotransmission to a pre-defined level in acute hippocampal brain slices incubated with 3 µM cCPA. This novel approach of closed-loop photopharmacology holds therapeutic potential for fine-tuned control of neurotransmission in diseases associated with neuronal hyperexcitability.

Citation

Erine Craey, Fabian Hulpia, Jeroen Spanoghe, Simona Manzella, Lars E Larsen, Mathieu Sprengers, Dimitri De Bundel, Ilse Smolders, Evelien Carrette, Jean Delbeke, Kristl Vonck, Paul Boon, Serge Van Calenbergh, Wytse J Wadman, Robrecht Raedt. Ex Vivo Feedback Control of Neurotransmission Using a Photocaged Adenosine A1 Receptor Agonist. International journal of molecular sciences. 2022 Aug 10;23(16)