Cholinergic Coordination of Presynaptic and Postsynaptic Activity Induces Timing-Dependent Hippocampal Synaptic Plasticity

Laboratory of Neurobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 09/2012; 32(36):12337-48. DOI: 10.1523/JNEUROSCI.2129-12.2012
Source: PubMed


Correlated presynaptic and postsynaptic activity is the key factor in inducing Hebbian plasticity and memory. However, little is known about the physiological events that could mediate such coordination. Correlated cholinergic input induces spike timing-dependent plasticity-like hippocampal synaptic plasticity. Cholinergic receptors are localized to both presynaptic and postsynaptic glutamatergic sites and thus have the potential to coordinate presynaptic and postsynaptic activity to induce plasticity. By directly monitoring presynaptic and postsynaptic activities with genetically encoded calcium indicators in mouse septohippocampal cocultures, we found interactive but independent presynaptic and postsynaptic modulations in the cholinergic-dependent synaptic plasticity. Neither presynaptic nor postsynaptic modulation alone is sufficient, but instead a coordinated modulation at both sites is required to induce the plasticity. Therefore, we propose that correlated cholinergic input can coordinate presynaptic and postsynaptic activities to induce timing-dependent synaptic plasticity, providing a novel mechanism by which neuromodulators precisely modulate network activity and plasticity with high efficiency and temporal precision.

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    • "Among the most abundant nAChRs are homopentameric α7-containing receptors (α7-nAChRs), which can be located both pre-and postsynaptically at many kinds of central synapses. The receptors can mediate synaptic plasticity; even brief activation of α7-nAChRs can induce long-term potentiation (LTP; Fuiji et al., 1999; Gu et al., 2012; Ji et al., 2001; Kenney and Gould, 2008; Placzek et al., 2009; Yakel, 2012). A common mechanism driving long-term synaptic plasticity is a change in the number or functionality of postsynaptic glutamate receptors at a glutamatergic synapse (Bear and Abraham, 1996; Bliss and Collingridge, 1993; Derkach et al., 2007; Lau and Zukin, 2007). "
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    • "The extrasynaptic localization of the a 7 receptor raises a question regarding the ACh concentration to which these receptors will be exposed in vivo together with the time course of such changes. Nonetheless, the relevance of the time-dependence function of a 7 receptors was illustrated using a different experimental paradigm, as recently shown by different studies in both the cortex and cerebellum (Gu and Yakel, 2011; Gu et al., 2012; Prestori et al., 2013). Modulation of the a 7 nAChR activity was shown to affect cognitive function and that agonist can restore drug-induced cognitive deficit (Freedman et al., 2008; Prickaerts et al., 2012). "
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    • "There are two types of AChRs: the nAChR and mAChR. Both receptors allow ACh to change the electrical activity of the target cells and to affect other processes through intracellular signaling cascades (Dajas-Bailador and Wonnacott, 2004; Gulledge and Stuart, 2005; Intskirveli and Metherate, 2012; Thiele, 2013; Yakel, 2013). However, these receptors function in fundamentally different ways. "
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