Poster Session 2 - B16
1Sridevi Venkatesan, 1Daniel W. Sparks, 1,2Evelyn K. Lambe
1 Department of Physiology, University of Toronto; 2 Department of Obstetrics and Gynaecology, University of Toronto, Toronto, ON, Canada
Layer 6 pyramidal neurons of the prefrontal cortex are excited robustly by acetylcholine(ACh) and are a major source of projections to the thalamus. Hence, they are postulated to be involved in top- down cholinergic modulation of attention. The α5 nicotinic receptor subunit encoded by Chrna5 is an accessory subunit that is heavily expressed in layer 6 of the PFC and may affect receptor conductance and desensitization properties. Previous studies have shown that α5 -/- mice are impaired during demanding attentional tasks. However, the role of Chrna5 in the cellular and network response to endogenous ACh is unknown. Here, we investigate the role of the α5 nicotinic subunit in the response to optogenetic cholinergic stimulation, using whole cell recordings in brain slices from littermate wildtype and α5-/- mice expressing channelrhodopsin2 in cholinergic neurons. Our results show that the response to light-evoked ACh release is significantly attenuated in α5-/- mice. Wild-type mice show a state of cholinergic-evoked persistent activity, which greatly exceeds the duration of light stimulation. Such activity is rare in α5-/- mice and has slower kinetics when it does occur. In voltage clamp, the inward current elicited by ACh release is reduced in the α5-/- mice. In ongoing work, we are probing the contributions of specific cholinergic receptors in relation to Chrna5 genotype. Taken together, these experiments will demonstrate the specific role of the α5 subunit in the cholinergic control of attention circuitry.