title: Priming locus coeruleus noradrenergic modulation of medial perforant path-dentate gyrus synaptic plasticity.
abstract: Priming phenomenon, in which an earlier exposure to a stimulus or condition alters synaptic plasticity in response to a subsequent stimulus or condition, known as a challenge, is an example of metaplasticity. In this review, we make the case that the locus coeruleus noradrenergic system-medial perforant path-dentate gyrus pathway is a neural ensemble amenable to studying priming-challenge effects on synaptic plasticity. Accumulating evidence points to a tyrosine hydroxylase-dependent priming effect achieved by pharmacological (nicotine and antipsychotics) or physiological (septal theta driving) manipulations of the locus coeruleus noradrenergic system that can facilitate noradrenaline-induced synaptic plasticity in the dentate gyrus of the hippocampus. The evidence suggests the hypothesis that behavioural experiences inducing tyrosine hydroxylase expression in the locus coeruleus may be sufficient to prime this form of metaplasticity. We propose exploring this phenomenon of priming and challenge physiologically, to determine whether behavioural experiences are sufficient to prime the locus coeruleus, enabling subsequent pharmacological or behavioural challenge conditions that increase locus coeruleus firing to release sufficient noradrenaline to induce long-lasting potentiation in the dentate gyrus. Such an approach may contribute to unravelling mechanisms underlying this form of metaplasticity and its importance in stress-related mnemonic processes.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 117600, Singapore; Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, 117456, Singapore; Singapore Institute for Neurotechnology (SINAPSE), 117456, Singapore.
authors.forename: Ramamoorthy
authors.initials: R
authors.lastname: Rajkumar
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 117600, Singapore; Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, 117456, Singapore; Singapore Institute for Neurotechnology (SINAPSE), 117456, Singapore; NUS Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore, 117456, Singapore.
authors.forename: Jigna Rajesh
authors.initials: JR
authors.lastname: Kumar
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 117600, Singapore; Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, 117456, Singapore; Singapore Institute for Neurotechnology (SINAPSE), 117456, Singapore; NUS Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore, 117456, Singapore. Electronic address: gavindawe@nus.edu.sg.
authors.forename: Gavin S
authors.initials: GS
authors.lastname: Dawe
mesh_terms: D059331:Adrenergic Neurons / Q000502:physiology*; D000818:Animals; D018891:Dentate Gyrus / Q000502:physiology*; D008125:Locus Coeruleus / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D019580:Perforant Pathway / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D014446:Tyrosine 3-Monooxygenase
keywords: Hippocampus; Locus coeruleus; Long-term potentiation; Metaplasticity; Priming; Stress