Norepinephrine triggers metaplasticity of LTP by increasing translation of specific mRNAs

Maity, Sabyasachi; Rah, Sean; Sonenberg, Nahum; Gkogkas, Christos G.; Nguyen, Peter V.

doi:10.1101/lm.039222.115

Cited by 46 publications

(56 citation statements)

References 78 publications

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“…Norepinephrine stabilizes heterosynaptic LTP NE binds to β-ARs to facilitate potentiation at excitatory hippocampal synapses (Stanton and Sarvey 1984;Harley et al 1996;Katsuki et al 1997). When applied before, or during, a single 100 Hz tetanus that normally elicits decremental LTP, NE enables the expression of long-lasting homosynaptic LTP in area CA1 of mouse hippocampal slices ("NE-LTP": Maity et al 2015Maity et al , 2016. Pairing ISO, a β-AR agonist, with one train of 100 Hz (Gelinas and Nguyen 2005;Gelinas et al 2007) or with low-frequency stimulation (Thomas et al 1996) also induces long-lasting homosynaptic LTP ("ISO-LTP").…”

Section: Resultsmentioning

confidence: 99%

“…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). In general, translation is critical for stabilizing LTP (Krug et al 1984;Costa-Mattioli et al 2009;Maity et al 2015).…”

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confidence: 99%

“…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). In general, translation is critical for stabilizing LTP (Krug et al 1984;Costa-Mattioli et al 2009;Maity et al 2015).…”

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confidence: 99%

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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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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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

Brandwein

Nguyen

2019

Learn. Mem.

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“…NA might shape the activation matrix of synapses and further response of synapses to new incoming stimuli, that is, in the murine CA1 region in vitro [63], a concept termed metaplasticity [64, 65]. Metaplasticity is a neurophysiologic phenomenon that serves to enable robust memories by selecting and filtering information via changes in synaptic plasticity.…”

Section: Memory Priming By Locus Coeruleus Activationmentioning

confidence: 99%

The Longevity of Hippocampus-Dependent Memory Is Orchestrated by the Locus Coeruleus-Noradrenergic System

Hansen

2017

Neural Plasticity

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The locus coeruleus is connected to the dorsal hippocampus via strong fiber projections. It becomes activated after arousal and novelty, whereupon noradrenaline is released in the hippocampus. Noradrenaline from the locus coeruleus is involved in modulating the encoding, consolidation, retrieval, and reversal of hippocampus-based memory. Memory storage can be modified by the activation of the locus coeruleus and subsequent facilitation of hippocampal long-term plasticity in the forms of long-term depression and long-term potentiation. Recent evidence indicates that noradrenaline and dopamine are coreleased in the hippocampus from locus coeruleus terminals, thus fostering neuromodulation of long-term synaptic plasticity and memory. Noradrenaline is an inductor of epigenetic modifications regulating transcriptional control of synaptic long-term plasticity to gate the endurance of memory storage. In conclusion, locus coeruleus activation primes the persistence of hippocampus-based long-term memory.

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“…Although we are unsure if the mechanism supporting this learning in human infants is the same as in rodents, there is some suggestion that NE’s role in attachment is a phylogenetically conserved system. NE has been shown to play a critical role in social bond formation throughout development in numerous species (Nelson & Panksepp, 1998; Numan & Young, 2016; Kaba & Huang, 2005; Corona & Levy, 2015; Calamandrei et al, 1992), as well as in modulation of learning throughout the lifespan (McGaugh, 2015; Maity et al, 2015; Shea et al, 2008; Gold, 2015). While children have high levels of NE during the first two years of life, the role of NE or any other hormone or neurotransmitter in early life attachment in humans is yet to be demonstrated, as it has been established by the rodent literature (Slotkin & Langercrantz, 1986).…”

Section: Neurobiology Of Attachment Learning: Odor Learning and Safetymentioning

confidence: 99%

The neurobiology of safety and threat learning in infancy

Dębiec

Sullivan

2017

Neurobiology of Learning and Memory

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What an animal needs to learn to survive is altered dramatically as they change from dependence on the parent for protection to independence and reliance on self-defense. This transition occurs in most altricial animals, but our understanding of the behavioral neurobiology has mostly relied on the infant rat. The transformation from dependence to independence occurs over three weeks in pups and is accompanied by complex changes in responses to both natural and learned threats and the supporting neural circuitry. Overall, in early life, the threat system is quiescent and learning is biased towards acquiring attachment related behaviors to support attachment to the caregiver and proximity seeking. Caregiver-associated cues learned in infancy have the ability to provide a sense of safety throughout lifetime. This attachment/safety system is activated by learning involving presumably pleasurable stimuli (food, warmth) but also painful stimuli (tailpinch, moderate shock). At about the midway point to independence, pups begin to have access to the adult-like amygdala-dependent threat system and amygdala-dependent responses to natural dangers such as predator odors. However, pups have the ability to switch between the infant and adult-like system, which is controlled by maternal presence and modification of stress hormones. Specifically, if the pup is alone, it will learn fear but if with the mother it will learn attachment (10–15 days of age). As pups begin to approach weaning, pups lose access to the attachment system and rely only on the amygdala-dependent threat system. However, pups learning system is complex and exhibits flexibility that enables the mother to override the control of the attachment circuit, since newborn pups may acquire threat responses from the mother expressing fear in their presence. Together, these data suggest that the development of pups’ threat learning system is not only dependent upon maturation of the amygdala, but it is also exquisitely controlled by the environment. Most notably the mother can switch pup learning between attachment to threat learning in a moment’s notice. This enables the mother to navigate pup’s learning about the world and what is threatening and what is safe.

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Norepinephrine triggers metaplasticity of LTP by increasing translation of specific mRNAs

Cited by 46 publications

References 78 publications

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

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

The Longevity of Hippocampus-Dependent Memory Is Orchestrated by the Locus Coeruleus-Noradrenergic System

The neurobiology of safety and threat learning in infancy

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