Axonal α7 nicotinic ACh receptors modulate presynaptic NMDA receptor expression and structural plasticity of glutamatergic presynaptic boutons
- 3 September 2010
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 107 (38), 16661-16666
- https://doi.org/10.1073/pnas.1007397107
Abstract
In association with NMDA receptors (NMDARs), neuronal α7 nicotinic ACh receptors (nAChRs) have been implicated in neuronal plasticity as well as neurodevelopmental, neurological, and psychiatric disorders. However, the role of presynaptic NMDARs and their interaction with α7 nAChRs in these physiological and pathophysiological events remains unknown. Here we report that axonal α7 nAChRs modulate presynaptic NMDAR expression and structural plasticity of glutamatergic presynaptic boutons during early synaptic development. Chronic inactivation of α7 nAChRs markedly increased cell surface NMDAR expression as well as the number and size of glutamatergic axonal varicosities in cortical cultures. These boutons contained presynaptic NMDARs and α7 nAChRs, and recordings from outside-out pulled patches of enlarged presynaptic boutons identified functional NMDAR-mediated currents. Multiphoton imaging of presynaptic NMDAR-mediated calcium transients demonstrated significantly larger responses in these enlarged boutons, suggesting enhanced presynaptic NMDAR function that could lead to increased glutamate release. Moreover, whole-cell patch clamp showed a significant increase in synaptic charge mediated by NMDAR miniature EPSCs but no alteration in the frequency of AMPAR miniature EPSCs, suggesting the selective enhancement of postsynaptically silent synapses upon inactivation of α7 nAChRs. Taken together, these findings indicate that axonal α7 nAChRs modulate presynaptic NMDAR expression and presynaptic and postsynaptic maturation of glutamatergic synapses, and implicate presynaptic α7 nAChR/NMDAR interactions in synaptic development and plasticity.This publication has 53 references indexed in Scilit:
- Organization of NMDA receptors at extrasynaptic locationsNeuroscience, 2010
- Age dependent nicotinic influences over dopamine neuron synaptic plasticityBiochemical Pharmacology, 2009
- A 2-base pair deletion polymorphism in the partial duplication of the α7 nicotinic acetylcholine gene (CHRFAM7A) on chromosome 15q14 is associated with schizophreniaBrain Research, 2009
- Presynaptic NMDA Receptors: Newly Appreciated Roles in Cortical Synaptic Function and PlasticityThe Neuroscientist, 2008
- Presynaptic and Postsynaptic NMDA Receptors Mediate Distinct Effects of Brain-Derived Neurotrophic Factor on Synaptic TransmissionJournal of Neurophysiology, 2008
- Desensitization of Nicotinic Acetylcholine Receptors as a Strategy for Drug DevelopmentThe Journal of pharmacology and experimental therapeutics, 2008
- Presynaptic Type III Neuregulin 1 Is Required for Sustained Enhancement of Hippocampal Transmission by Nicotine and for Axonal Targeting of α7 Nicotinic Acetylcholine ReceptorsJournal of Neuroscience, 2008
- Chronic nicotine exposure induces a long-lasting and pathway-specific facilitation of LTP in the amygdalaLearning & Memory, 2008
- Presynaptic Type III Neuregulin1-ErbB signaling targets α7 nicotinic acetylcholine receptors to axonsThe Journal of cell biology, 2008
- Synaptic Specificity Is Generated by the Synaptic Guidepost Protein SYG-2 and Its Receptor, SYG-1Cell, 2004