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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    • "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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    ABSTRACT: Acetylcholine (ACh) release in the medial prefrontal cortex (mPFC) is crucial for normal cognitive performance. Despite the fact that many have studied how ACh affects neuronal processing in the mPFC and thereby influences attention behavior, there is still a lot unknown about how this occurs. Here we will review the evidence that cholinergic modulation of the mPFC plays a role in attention and we will summarize the current knowledge about the role between ACh receptors (AChRs) and behavior and how ACh receptor activation changes processing in the cortical microcircuitry. Recent evidence implicates fast phasic release of ACh in cue detection and attention. This review will focus mainly on the fast ionotropic nicotinic receptors and less on the metabotropic muscarinic receptors. Finally, we will review limitations of the existing studies and address how innovative technologies might push the field forward in order to gain understanding into the relation between ACh, neuronal activity and behavior.
    Frontiers in Neural Circuits 03/2014; 8:17. DOI:10.3389/fncir.2014.00017 · 3.60 Impact Factor
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    • "As well as directly causing short- and long-term synaptic plasticity, cholinergic receptor activation modulates the induction of synaptic plasticity (Shimoshige et al., 1997; Leung et al., 2003; Ovsepian et al., 2004; Ge and Dani, 2005; Shinoe et al., 2005). The precise mechanism and direction of modulation may depend on acetylcholine concentration, the timing of its release, exposure time and the temporal sequence of nAChRs and mAChRs activation in relation to ongoing neuronal activity (Fujii and Sumikawa, 2001; Ge and Dani, 2005; Gu and Yakel, 2011; Gu et al., 2012). A number of mechanisms have been proposed for the modulation of synaptic plasticity. "
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    ABSTRACT: Cholinergic septohippocampal projections from the medial septal area to the hippocampus are proposed to have important roles in cognition by modulating properties of the hippocampal network. However, the precise spatial and temporal profile of acetylcholine release in the hippocampus remains unclear making it difficult to define specific roles for cholinergic transmission in hippocampal dependent behaviors. This is partly due to a lack of tools enabling specific intervention in, and recording of, cholinergic transmission. Here, we review the organization of septohippocampal cholinergic projections and hippocampal acetylcholine receptors as well as the role of cholinergic transmission in modulating cellular excitability, synaptic plasticity, and rhythmic network oscillations. We point to a number of open questions that remain unanswered and discuss the potential for recently developed techniques to provide a radical reappraisal of the function of cholinergic inputs to the hippocampus.
    Frontiers in Synaptic Neuroscience 07/2013; 5:2. DOI:10.3389/fnsyn.2013.00002
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    ABSTRACT: The neurotransmitter acetylcholine (ACh) can regulate neuronal excitability throughout the nervous system by acting on both the cys-loop ligand-gated nicotinic ACh receptor channels (nAChRs) and the G protein-coupled muscarinic ACh receptors (mAChRs). The hippocampus is an important area in the brain for learning and memory, where both nAChRs and mAChRs are expressed. The primary cholinergic input to the hippocampus arises from the medial septum and diagonal band of Broca, the activation of which can activate both nAChRs and mAChRs in the hippocampus and regulate synaptic communication and induce oscillations that are thought to be important for cognitive function. Dysfunction in the hippocampal cholinergic system has been linked with cognitive deficits and a variety of neurological disorders and diseases, including Alzheimer's disease and schizophrenia. My lab has focused on the role of the nAChRs in regulating hippocampal function, from understanding the expression and functional properties of the various subtypes of nAChRs, and what role these receptors may be playing in regulating synaptic plasticity. Here, I will briefly review this work, and where we are going in our attempts to further understand the role of these receptors in learning and memory, as well as in disease and neuroprotection.
    Pflügers Archiv - European Journal of Physiology 01/2013; 465(4). DOI:10.1007/s00424-012-1200-1 · 4.10 Impact Factor
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