Nicotine induces dendritic spine remodeling in cultured hippocampal neurons
Article first published online: 24 OCT 2013
© 2013 International Society for Neurochemistry
Journal of Neurochemistry
Volume 128, Issue 2, pages 246–255, January 2014
How to Cite
J. Neurochem. (2014) 128, 246–255.
- Issue published online: 6 JAN 2014
- Article first published online: 24 OCT 2013
- Accepted manuscript online: 1 OCT 2013 12:55AM EST
- Manuscript Accepted: 13 SEP 2013
- Manuscript Revised: 11 SEP 2013
- Manuscript Received: 20 MAY 2013
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- Takeda Science Foundation
- cultured hippocampal neurons;
- dendritic spine remodeling;
- glutamatergic neurotransmission;
- synaptic plasticity;
- α4β2* nAChR
Cholinergic neurons in the CNS are involved in synaptic plasticity and cognition. Both muscarinic and nicotinic acetylcholine receptors (nAChRs) influence plasticity and cognitive function. The mechanism underlying nAChR-induced plasticity, however, has remained elusive. Here, we demonstrate morphological changes in dendritic spines following activation of α4β2* nAChRs, which are expressed on glutamatergic pre-synaptic termini of cultured hippocampal neurons. Exposure of the neurons to nicotine resulted in a lateral enlargement of spine heads. This was abolished by dihydro-β-erythroidine, an antagonist of α4β2* nAChRs, but not by α-bungarotoxin, an antagonist of α7 nAChRs. Tetanus toxin or a mixture of 2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione, antagonists of NMDA- and AMPA-type glutamate receptors, blocked the nicotine-induced spine remodeling. In addition, nicotine exerted full spine-enlarging response in the post-synaptic neuron whose β2 nAChR expression was knocked down. Finally, pre-treatment with nicotine enhanced the Ca2+-response of the neurons to glutamate. These data suggest that nicotine influences the activity of glutamatergic neurotransmission through the activation of pre-synaptic α4β2 nAChRs, resulting in the modulation of spinal architecture and responsiveness. The present findings may represent one of the cellular mechanisms underlying cholinergic tuning of brain function.
Activation of nicotinic acetylcholine receptors (nAChRs) in brain influences plasticity and cognition. Here, activation of α4β2* nAChRs, which are expressed on glutamatergic presynaptic termini, results in the enlargement of dendritic spines through the modulation of the glutamatergic neurotransmission. The remodeled spinal architecture might be responsible for the change in responsiveness of neural circuitry, leading to cholinergic tuning of brain function.