1. Long-term effects of early postnatal nicotine exposure on cholinergic function in the mouse hippocampal CA1 region.
- Author
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Nakauchi S, Su H, Trang I, and Sumikawa K
- Subjects
- Animals, Animals, Newborn, CA1 Region, Hippocampal growth & development, CA1 Region, Hippocampal metabolism, Cigarette Smoking, Excitatory Postsynaptic Potentials drug effects, Excitatory Postsynaptic Potentials physiology, Female, Lactation, Long-Term Synaptic Depression physiology, Male, Maternal Exposure, Memory drug effects, Memory physiology, Mice, Mice, Knockout, Receptor, Muscarinic M1 metabolism, Receptors, Metabotropic Glutamate drug effects, Receptors, Metabotropic Glutamate metabolism, Receptors, Muscarinic drug effects, Receptors, Muscarinic metabolism, Receptors, N-Methyl-D-Aspartate drug effects, Receptors, N-Methyl-D-Aspartate metabolism, Receptors, Nicotinic metabolism, CA1 Region, Hippocampal drug effects, Long-Term Synaptic Depression drug effects, Nicotine pharmacology, Nicotinic Agonists pharmacology, Receptor, Muscarinic M1 drug effects, Receptors, Nicotinic drug effects
- Abstract
In rodent models of smoking during pregnancy, early postnatal nicotine exposure results in impaired hippocampus-dependent memory, but the underlying mechanism remains elusive. Given that hippocampal cholinergic systems modulate memory and rapid development of hippocampal cholinergic systems occurs during nicotine exposure, here we investigated its impacts on cholinergic function. Both nicotinic and muscarinic activation produce transient or long-lasting depression of excitatory synaptic transmission in the hippocampal CA1 region. We found that postnatal nicotine exposure impairs both the induction and nicotinic modulation of NMDAR-dependent long-term depression (LTD). Activation of muscarinic receptors decreases excitatory synaptic transmission and CA1 network activity in both wild-type and α2 knockout mice. These muscarinic effects are still observed in nicotine-exposed mice. M1 muscarinic receptor activity is required for mGluR-dependent LTD. Early postnatal nicotine exposure has no effect on mGluR-dependent LTD induction, suggesting that it has no effect on the function of m1 muscarinic receptors involved in this form of LTD. Our results demonstrate that early postnatal nicotine exposure has more pronounced effects on nicotinic function than muscarinic function in the hippocampal CA1 region. Thus, impaired hippocampus-dependent memory may arise from the developmental disruption of nicotinic cholinergic systems in the hippocampal CA1 region., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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