Nicotine Enhances Firing Activity of Layer 5 Pyramidal Neurons in the Medial Prefrontal Cortex through Inhibition of Kv7 Channels

Nicotine enhances attention, working memory and recognition. One of the brain regions associated with these effects of nicotine is the medial prefrontal cortex (mPFC). However, cellular mechanisms that induce the enhancing effects of nicotine remain unclear. To address this issue, we performed whole-cell patch-clamp recordings from mPFC layer 5 pyramidal neurons in slices of C57BL/6J mice. Shortly (approx. 2min) after bath application of nicotine, the number of action potentials, which were elicited by depolarizing current injection, was increased, and this increase persisted for over 5min. The effect of nicotine was blocked by the alpha 4 beta 2 nicotinic acetylcholine receptor (nAChR) antagonist dihydro-beta-erythroidine, alpha 7 nAChR antagonist methyllycaconitine, or intracellular perfusion with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N',N',N',N'-tetraacetic acid (BAPTA). Additionally, the voltage-dependent potassium 7 (Kv7) channel blocker, 10,10-bis(4-pyridinylmethyl)-9(10H-anthracenone dihydrochloride (XE-991), as well as nicotine, shortened the spike threshold latency and increased the spike numbers. By contrast, the Kv7 channel opener, retigabine reduced the number of firings, and the addition of nicotine did not increase the spike numbers. These results indicate that nicotine induces long-lasting enhancement of firing activity in mPFC layer 5 pyramidal neurons, which is mediated by the stimulation of the alpha 4 beta 2 and alpha 7 nAChRs and subsequent increase in intracellular Ca2+ levels followed by the suppression of the Kv7 channels. The novel effect of nicotine might underlie the nicotine-induced enhancement of attention, working memory and recognition.

Automated summary

Nicotine enhances firing activity in mPFC layer 5 pyramidal neurons by activating alpha 4 beta 2 and alpha 7 nAChRs, increasing intracellular Ca2+ levels, and suppressing Kv7 channels, which may be the underlying mechanism for nicotine-induced enhancement of attention, working memory and recognition.