Selective Extracellular Stimulation of Pharmacologically Distinct CCK/CB1R Positive Interneuron to Pyramidal Cell Perisomatic Inhibitory Synapses

Abstract

© 2016, Springer Science+Business Media New York.During prolonged whole cell recording, the intracellular contents are progressively dialyzed with the pipette solution; this often leads to significant changes in synaptic efficacy. To overcome this problem, we developed an approach allowing reliable extracellular stimulation of perisomatic synapses formed by CCK+/CB1+ interneurons onto CA1 pyramidal cells. Functional identification of this input was based on the unique features of CCK+/CB1+ terminals: long-lasting asynchronous transmitter release following high-frequency stimulation and exclusive expression of CB1R. Asynchronous release was used as an indication of proper positioning of the theta glass stimulation pipettes. We found that all extracellularly stimulated inputs with characteristic asynchronous release undergo robust DSI in response to 5-s depolarization and could also be almost entirely blocked by application of the CB1R agonist CP55940, which were similar to the data obtained with paired recordings from connected CB1+ and CA1 pyramidal cells. Thus, we have developed an approach allowing the selective and reliable extracellular stimulation of a subtype of hippocampal perisomatic inhibitory synapses.