Optimisation of photostimulation targeting muscarinic and glutamate receptors

The cholinergic system is critically involved in the modulation of cognitive functions. The central role of acetylcholine in cognition seems to be related to the synchronization of gamma band oscillations: gamma band power increases in relation to working memory load and abnormal gamma oscillations are associated with cognitive deficits. It has been demonstrated that muscarinic agonists can improve the frequency, and decrease the duration and the power of slow waves (delta). This balance of neuromodulator levels plays a key role in sleep and memory (Vakalopoulos C et al., Front Neurosci 2014, 8, 63). Carbachol, a cholinergic agonist, has been shown to stabilize gamma frequency oscillations. To modulate brainwaves in neural circuits, IBEC, in collaboration with IDIBAPS, designed and prepared novel light-regulated agonists of muscarinic receptors, and tested their efficacy in cells and brain slices under different wavelengths of light irradiation. Data collected comes from three different experiments. The first one is a study which aims to characterize the effect produced on neural activity when the PAI molecule (Phthalimide-Azo-Iperoxo) in its cis and trans configuration is applied. Mainly, for the whole set of experiments, drugs are applied to the primary visual cortex coronal slices from ferret. The second experiment pretends to study the effect of an increasing concentration of both PAI molecule configurations: cis and trans. Finally, the third one tries to study the effect of another molecule (IPEROXO) on the same cortical slices under different concentrations.