The cholinergic system and hippocampal plasticity

School of Medical Sciences, College of Life Sciences and Medicine, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK.
Behavioural brain research (Impact Factor: 3.03). 12/2010; 221(2):505-14. DOI: 10.1016/j.bbr.2010.11.037
Source: PubMed


Acetylcholine is an essential excitatory neurotransmitter in the central nervous system and undertakes a vital role in cognitive function. Consequently, there is ample evidence to suggest the involvement of both nicotinic and muscarinic acetylcholine receptors in the modulation of synaptic plasticity, which is believed to be the molecular correlate of learning and memory. In the hippocampus in particular, multiple subtypes of both nicotinic and muscarinic receptors are present at presynaptic and postsynaptic loci of both principal neurons and inhibitory interneurons, where they exert profound bi-directional influences on synaptic transmission. Further evidence points to a role for cholinergic activation in the induction and maintenance of synaptic plasticity, and key influences on hippocampal network oscillations. The present review examines these multiple roles of acetylcholine in hippocampal plasticity.

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    • "This yielded an interpretation that dopaminergic neurons encode the " actual minus predicted reward " (Schultz, 2002). Acetylcholine is necessary to induce plasticity in sensory cortices (Gu, 2002) and hippocampus (Drever et al., 2011) as shown in a variety of paradigms including sensory map remodeling in auditory cortex (Kilgard and Merzenich, 1998;Ma and Suga, 2005) or inhibitory avoidance training (Mitsushima et al., 2013). Similarly, noradrenaline and serotonin play a permissive and facilitatory role for the induction of plasticity (Seidenbacher et al., 1997;Gu, 2002; Tully and Bolshakov, 2010;Bergado et al., 2011). "
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    ABSTRACT: Classical Hebbian learning puts the emphasis on joint pre- and postsynaptic activity, but neglects the potential role of neuromodulators. Since neuromodulators convey information about novelty or reward, the influence of neuromodulatorson synaptic plasticity is useful not just for action learning in classical conditioning, but also to decide 'when' to create new memories in response to a flow of sensory stimuli. In this review, we focus on timing requirements for pre- and postsynaptic activity in conjunction with one or several phasic neuromodulatory signals. While the emphasis of the text is on conceptual models and mathematical theories, we also discuss some experimental evidence for neuromodulation of Spike-Timing-Dependent Plasticity. We highlight the importance of synaptic mechanisms in bridging the temporal gap between sensory stimulation and neuromodulatory signals, and develop a framework for a class of neo-Hebbian three-factor learning rules that depend on presynaptic activity, postsynaptic variables as well as the influence of neuromodulators.
    Preview · Article · Jan 2016 · Frontiers in Neural Circuits
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    • "). Activation of each type of nAChR in glutamatergic neurons enhances post-synaptic responses and cellular plasticity (Drever et al., 2011). Rodent studies have shown that α7 nAChRs on inhibitory GABAergic (gamma-aminobutyric acid) interneurons are essential for normal auditory gating (Alkondon et al., 2000), and also that reduced receptor expression deficits could be partially ameliorated by agonism of the receptor (Stevens et al., 1998). "
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    ABSTRACT: Most individuals with schizophrenia suffer some cognitive dysfunction: such deficits are predictive of longer-term functioning; and current dopamine-blocking antipsychotics have made little impact on this domain. There is a pressing need to develop novel pharmacological agents to tackle this insidious but most disabling of problems. The acetylcholinergic system is involved in cognitive and attentional processing, and its metabotropic and nicotinic receptors are widespread throughout the brain. Deficits in acetylcholinergic functioning occur in schizophrenia, and high rates of tobacco smoking have been posited to represent a form of self-medication. The nicotinic acetylcholine receptor (nAChR) has emerged as a putative target to improve cognitive deficits in schizophrenia, and this study systematically reviewed the emerging data. Nineteen studies were identified, covering three compound classes: agonists at the α7 and α 4β2 nAChRs, and positive allosteric modulators. Overall data are underwhelming: some studies showed significant improvements in cognition but as many studies had negative findings. It remains unclear if this represents drug limitations or nascent study methodology problems. The literature is particularly hindered by variability in inclusion of smokers, generally small sample sizes, and a lack of consensus on cognitive test batteries. Future work should evaluate longer-term outcomes, and, particularly, the effects of concomitant cognitive training. © The Author(s) 2015.
    Full-text · Article · Jan 2015 · Journal of Psychopharmacology
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    • "Metab Brain Dis ChAT expression but did not show significant effect against AchE level. The diverse function of (M1) AchR and its occurrence in the hippocampus, suggests that (M1) AchR play a key role in learning and memory (Drever et al. 2011) and is known to transiently enhance long-term potentiation resulting in neurocognitive improvement (Anisuzzaman et al. 2013). Administration of selective (M1) AchR antagonists induces spatial memory deficit (Hunter and Roberts 1988). "
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    ABSTRACT: Diabetes mellitus is a chronic metabolic disorder and has been associated with cognitive dysfunction. In our earlier study, chronic Urtica dioica (UD) treatment significantly ameliorated diabetes induced associative and spatial memory deficit in mice. The present study was designed to explore the effect of UD leaves extract on muscarinic cholinergic system, which has long been known to be involved in cognition. Streptozotocin (STZ) (50 mg/kg, i.p., consecutively for 5 days) was used to induce diabetes followed by treatment with UD extract (50 mg/kg, oral) or rosiglitazone (5 mg/kg, oral) for 8 weeks. STZ-induced diabetic mice showed significant reduction in hippocampal muscarinic acetylcholine receptor-1 and choline acetyltransferase expressions. Chronic diabetes significantly up-regulated the protein expression of acetylcholinesterase associated with oxidative stress in hippocampus. Besides, STZ-induced diabetic mice showed hypolocomotion with up-regulation of muscarinic acetylcholine receptor-4 expression in striatum. Chronic UD treatment significantly attenuated the cholinergic dysfunction and oxidative stress in the hippocampus of diabetic mice. UD had no effect on locomotor activity and muscarinic acetylcholine receptor-4 expression in striatum. In conclusion, UD leaves extract has potential to reverse diabetes mediated alteration in muscarinic cholinergic system in hippocampus and thereby improve memory functions.
    Full-text · Article · Dec 2014 · Metabolic Brain Disease
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