Abstract
Chronic nicotine exposure has been shown to improve memory in rodents. However, the molecular mechanism for such an enhancement remains poorly understood. Chronic nicotine exposure increases NMDA/AMPA ratio due to enhanced NMDAR-mediated responses in hippocampal CA1 pyramidal cells and facilitates LTP. Here, we found that the same nicotine treatment increases NMDA/AMPA ratios in parvalbumin-expressing interneurons in the hippocampus and in layer 5 pyramidal cells in the medial prefrontal cortex (mPFC) of male and female rats. To gain further insight into the nicotine-initiated signaling pathway, we used a positive allosteric modulator (PAM) of m1 muscarinic acetylcholine receptor (m1 receptor), VU0453595. We found that chronic VU0453595 treatment mimics the effects of chronic nicotine exposure, causing increased NMDA/AMPA ratio in hippocampal CA1 pyramidal cells and LTP facilitation. Furthermore, chronic exposure to VU0453595 also caused increased NMDA/AMPA ratio in layer 5 pyramidal cells of mPFC. As the PAM only activates m1 receptors when the endogenous agonist acetylcholine (ACh) is present, the findings suggest that the release of ACh from cholinergic neurons is involved in the effect. Thus, chronic nicotine exposure, by increasing ACh release, may stimulate a signaling pathway in various neuron types, which receive cholinergic input and express m1 receptors, leading to the enhancement of NMDAR responses. The nicotine-initiated signaling pathway, in which ACh and m1 receptors are downstream of nicotinic ACh receptor activation, may represent an important cholinergic pathway involved in cognitive function.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.