Noradrenaline goes nuclear: epigenetic modifications during long‐lasting synaptic potentiation triggered by activation of β‐adrenergic receptors

Maity, Sabyasachi; Jarome, Timothy J.; Blair, Jessica; Lubin, Farah D.; Nguyen, Peter V.

doi:10.1113/jp271432

Cited by 39 publications

(43 citation statements)

References 96 publications

(117 reference statements)

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“…33 Catecholamine-synthesizing neurons may be central to these processes: norepinephrine has been demonstrated, in hippocampal memory cells, to induce long-term synaptic potentiation via epigenetic mechanisms. 34 One region richly populated by adrenergic neurons is the rostral ventrolateral medulla, a key autonomic node with projections to hypothalamic regions and the spinal cord. 35 A second, intimately involved in arousal and alertness, is the locus coeruleus.…”

Section: Discussionmentioning

confidence: 99%

“…33 Las neuronas que sintetizan catecolaminas pueden ser centrales en estos procesos: se ha demostrado que la noradrenalina, en las células de memoria del hipocampo, induce potenciación a largo plazo mediante mecanismos epigenéticos. 34 La porción rostral ventrolateral del bulbo raquídeo es una región intensamente poblada por neuronas adrenérgicas y es un nudo autónomo clave con proyecciones a regiones hipotalámicas y a la médula espinal. 35 El locus coeruleus es una segunda región íntimamente involucrada en el despertar y el estado de vigilancia.…”

Section: Discussionunclassified

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Arousal From Sleep and Sympathetic Excitation During Wakefulness

et al. 2016

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Obstructive apnea during sleep elevates the set point for efferent sympathetic outflow during wakefulness. Such resetting is attributed to hypoxia-induced upregulation of peripheral chemoreceptor and brain stem sympathetic function. Whether recurrent arousal from sleep also influences daytime muscle sympathetic nerve activity is unknown. We therefore tested, in a cohort of 48 primarily nonsleepy, middle-aged, male (30) and female (18) volunteers (age: 59±1 years, mean±SE), the hypothesis that the frequency of arousals from sleep (arousal index) would relate to daytime muscle sympathetic burst incidence, independently of the frequency of apnea or its severity. Polysomnography identified 24 as having either no or mild obstructive sleep apnea (apnea–hypopnea index <15 events/h) and 24 with moderate-to-severe obstructive sleep apnea (apnea–hypopnea index >15 events/h). Burst incidence correlated significantly with arousal index ( r =0.53; P <0.001), minimum oxygen saturation ( r =−0.43; P =0.002), apnea–hypopnea index ( r =0.41; P =0.004), age ( r =0.36; P =0.013), and body mass index ( r =0.33; P =0.022) but not with oxygen desaturation index ( r =0.28; P =0.056). Arousal index was the single strongest predictor of muscle sympathetic nerve activity burst incidence, present in all best subsets regression models. The model with the highest adjusted R 2 (0.456) incorporated arousal index, minimum oxygen saturation, age, body mass index, and oxygen desaturation index but not apnea–hypopnea index. An apnea- and hypoxia-independent effect of sleep fragmentation on sympathetic discharge during wakefulness could contribute to intersubject variability, age-related increases in muscle sympathetic nerve activity, associations between sleep deprivation and insulin resistance or insomnia and future cardiovascular events, and residual adrenergic risk with persistence of hypertension should therapy eliminate obstructive apneas but not arousals.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionunclassified

Arousal From Sleep and Sympathetic Excitation During Wakefulness

et al. 2016

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“…A recent study showed that tDCS induces epigenetic changes, including the BDNF locus in the mouse brain 12 . Considering another recent report that noradrenergic β receptor signaling promotes NMDAR-dependent long-term potentiation through epigenetic changes in neurons, 40 tDCS-induced noradrenergic signaling conceivably contributes to neural plasticity and epigenetic modifications, in consort with the astrocyte-mediated signaling.…”

Section: Introductionmentioning

confidence: 99%

Astrocytic calcium activation in a mouse model of tDCS—Extended discussion

Monai

Hirase

2016

Neurogenesis

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Transcranial direct current stimulation (tDCS) has been reported to be effective for alleviation of neuropsychiatric and neurological conditions as well as enhancement of memory and cognition. Despite the positive effects of tDCS in humans, its mechanism of action remains poorly understood. Recently, we reported that astrocytes, a major glial cell type in the brain, show an increase in intracellular Ca2+ levels during tDCS in the cerebral cortex of the awake mouse. This tDCS-induced elevation in astrocytic Ca2+ has subsequently been demonstrated to be important for cortical plasticity. In this commentary article, we discuss possible interpretations and implications of our findings from the viewpoint of neuron-glia interactions.

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“…One type of hippocampal synaptic plasticity is long-term potentiation (LTP) (Bliss and Lømo 1973). LTP is believed to be a cellular mechanism for memory formation in the mammalian brain (Bliss and Collingridge 1993;Bourtchuladze et al 1994;Ji et al 2003a;Gelinas and Nguyen 2005;Whitlock et al 2006; for review, see Martin et al 2000), and it can be sustained by treating in vitro hippocampal slices with either a β-AR agonist, isoproterenol (ISO) (Thomas et al 1996;Katsuki et al 1997;Gelinas and Nguyen 2005), or with the natural β-AR ligand, NE (Katsuki et al 1997;Hu et al 2007;Maity et al 2016;for review, see O'Dell et al 2015). Furthermore, β-AR activation by ISO or NE boosts the endurance of LTP by activating signaling kinases to modulate translation initiation and increase the synthesis of specific proteins (Winder et al 1999;Klann et al 2004;Gelinas et al 2007;Maity et al 2015;for review, see O'Dell et al 2015).…”

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confidence: 99%

Noradrenergic stabilization of heterosynaptic LTP requires activation of Epac in the hippocampus

Brandwein

Nguyen

2019

Learn. Mem.

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Beta-adrenergic receptor (β-AR) activation by norepinephrine (NE) enhances memory and stabilizes long-term potentiation (LTP), a form of synaptic plasticity believed to underlie some forms of hippocampal memory. LTP can occur at multiple synaptic pathways as a result of strong stimulation to one pathway preceding milder stimulation of an adjacent, independent pathway. Synaptic tagging allows LTP to be transferred, or captured, at heterosynaptic pathways. Previous research has shown that β-AR activation promotes heterosynaptic LTP by engaging various signaling cascades. In particular, cyclic adenosine monophosphate (cAMP) activates cAMP-dependent protein kinase A (PKA) and guanine nucleotide exchange protein activated by cAMP (Epac), to enhance LTP. Epac activation can occlude subsequent induction of stable homosynaptic LTP after β-AR activation, but it is unclear whether Epac activation is required for heterosynaptic LTP following pairing of the natural transmitter, NE, with one 100 Hz train of stimulation ("NE-LTP"). Using electrophysiologic recordings of CA1 field excitatory postsynaptic potentials during stimulation of two independent synaptic pathways in murine hippocampal slices, we show that distinct inhibitors of Epac blocked stabilization of homo-and heterosynaptic NE-LTP. PKA inhibition also attenuated heterosynaptic transfer of NE-LTP, but only when a PKA inhibitor was applied during tetanization of a second, heterosynaptic pathway that was not treated with NE. Our data suggest that NE, paired with 100 Hz, activates Epac to stabilize homo-and heterosynaptic LTP. Epac may regulate the production of plasticity-related proteins and subsequent synaptic capture of NE-LTP at a heterosynaptic pathway. Epac activation under these conditions may enable behavioral experiences that engage noradrenergic inputs to hippocampal circuits to be transformed into stable long-term memories.

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Noradrenaline goes nuclear: epigenetic modifications during long‐lasting synaptic potentiation triggered by activation of β‐adrenergic receptors

Cited by 39 publications

References 96 publications

Arousal From Sleep and Sympathetic Excitation During Wakefulness

Arousal From Sleep and Sympathetic Excitation During Wakefulness

Astrocytic calcium activation in a mouse model of tDCS—Extended discussion

Noradrenergic stabilization of heterosynaptic LTP requires activation of Epac in the hippocampus

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