High-Affinity Nicotinic Receptors Modulate Spontaneous Cortical Up States In Vitro.

Through our experiments we were able to uncover a clear and previously disputed effect of nicotinic signaling in synchronized activity of neuronal networks of the cortex. We show that both high-affinity receptors (containing the β2-subunit, β2-nAChRs) and low-affinity receptors (containing the α7-subunit, α7-nAChRs) can regulate cortical network function exhibited in the form of Up/Down states. We further show that the effects of β2-nAChRs, but not α7-nAChRs, are mediated through the activation of GABAB receptors. These results suggest a possible synthesis of seemingly contradictory results in the literature and could be valuable for informing computational models of cortical function and for guiding the search for therapeutic interventions.