The Transition from Stochastic to Collective Activation of Nicotinic Acetylcholine Receptors Facilitates Information Transmission Within in vitro Hippocampal Networks

Abstract

Although modulatory in nature, nicotinic acetylcholine receptors (nAChRs) play a major role in the central nervous system, making them one of the most studied receptor class. While both activation and desensitization are phenomena associated with the functions of individual receptors, their effects will clearly manifest on the network/circuit spatial scale. In this study, nicotine was used to investigate the impact of activation and desensitization of nAChRs on cultured hippocampal networks. We assess network dynamics via the recording of extracellular action potentials using a microelectrode array system (MEA). We bath applied either a single dose or two successive doses of increasing concentration of nicotine. We hypothesize that a high concentration of nicotine will facilitate information transmission but pre‐incubation of the network with a low concentration of nicotine would attenuate facilitation. We show that the low concentration has minimal effects on network activity and we call this a network‐desensitized state. A high concentration significantly impacted both spiking and bursting activity and we call this a network‐activated state. Interestingly, a low concentration pre‐incubation of nicotine blocked or significantly diminished activity when followed by a high concentration. Lastly, network synchronization as well as network efficiency increased with the large nicotine concentration. This suggests that although fleeting, the process of global receptor activation has a longer lasting impact on the network than a stochastic receptor activation.Support or Funding InformationNational Science Foundation grant no. PHY‐1205919