Locus Ceruleus Activation Initiates Delayed Synaptic Potentiation of Perforant Path Input to the Dentate Gyrus in Awake Rats: A Novel β-Adrenergic- and Protein Synthesis-Dependent Mammalian Plasticity Mechanism

Walling, Susan G.; Harley, Carolyn W.

doi:10.1523/jneurosci.4426-03.2004

Cited by 103 publications

(78 citation statements)

References 58 publications

(60 reference statements)

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“…Through combined application of b-adrenergic and muscarinic receptor agonists, LTP induced by low-frequency stimulation (5 Hz, 5 sec) was significantly enhanced relative to slices treated with stimulation alone, or stimulation paired with either agonist alone. The functional importance of this form of LTP is demonstrated by a requirement for translation which links this form of LTP to evidence implicating protein synthesis-dependent LTP in long-term memory formation (Abel et al 1997;Straube et al 2003;Walling and Harley 2004;Herrera-Morales et al 2007).…”

Section: Discussionmentioning

confidence: 97%

“…Noradrenaline activates a-and b-adrenergic receptors which can, likewise, elicit opposing effects on cell excitability and synaptic plasticity (Gelinas et al 2008;Lemon et al 2009). Activation of either muscarinic (Shinoe et al 2005;Li et al 2007;Poulin et al 2010) or b-adrenergic receptors (Thomas et al 1996;Walling and Harley 2004;Gelinas and Nguyen 2005;Lemon et al 2009) can enhance synaptic strength and memory formation.…”

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confidence: 99%

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Conversion of short-term potentiation to long-term potentiation in mouse CA1 by coactivation of β-adrenergic and muscarinic receptors

et al. 2012

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Encoding new information requires dynamic changes in synaptic strength. The brain can boost synaptic plasticity through the secretion of neuromodulatory substances, including acetylcholine and noradrenaline. Considerable effort has focused on elucidating how neuromodulatory substances alter synaptic properties. However, determination of the potential synergistic interactions between different neuromodulatory systems remains incomplete. Previous results indicate that coactivation of badrenergic and cholinergic receptors facilitated the conversion of STP to LTP through an extracellular signal-regulated kinase (ERK)-dependent mechanism. ERK signaling has been linked to synaptically localized translation regulation. Thus, we hypothesized that costimulation of noradrenergic and cholinergic receptors could initiate the transformation of STP to LTP through up-regulation of protein synthesis. Our results indicate that a protocol which yields STP (5 Hz, 5 sec) when paired with coapplication of the b-adrenergic agonist, isoproterenol (ISO), and the cholinergic agonist, carbachol (CCh), induces translationdependent LTP in mouse CA1. This form of LTP requires both b1-adrenergic and M1 muscarinic receptor activation, as blocking either receptor subtype prevented LTP induction. Blocking ERK, mTOR, or translation reduced the expression of LTP induced with ISO + CCh. Taken together, our data demonstrate that coactivation of b-adrenergic and muscarinic receptors facilitates the conversion of STP to LTP through a mechanism requiring translation initiation.Memory formation is believed to rely on an activity-dependent, enduring modification of synaptic strength known as long-term potentiation (LTP) (Bliss and Lomo 1973;Bliss and Collingridge 1993;Kandel 2001). LTP has been demonstrated in the hippocampus following events which induce behavioral changes indicative of learning and memory (Whitlock et al. 2006). The hippocampus plays a time-limited role in the establishment of new memories (Scoville and Milner 1957;Zola-Morgan et al. 1986;Neves et al. 2008), a process subject to modification through the release of neuromodulatory transmitters.Cholinergic and noradrenergic neuromodulatory systems can enhance synaptic plasticity (Hu et al. 2007;Dringenberg et al. 2008;Fernández de Sevilla et al. 2008) and long-term memory formation (Cahill et al. 1994 Although the individual contributions of b-and muscarinic receptors to synaptic function have been investigated, the effects of simultaneous activation of these receptors have yet to be fully elucidated. Previous research has demonstrated that coactivation of a-adrenergic and muscarinic receptors facilitates the induction of long-term depression (LTD) (Scheiderer et al. 2008). LTD induced by a-adrenergic and M1 receptors is facilitated through a synergistic elevation of extracellular signal-regulated kinase (ERK) phosphorylation. A similar effect on ERK stimulation was observed when the b-adrenergic receptor agonist, isoproterenol (ISO), was paired with carbachol (CCh), a broad-spectrum mu...

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Section: Discussionmentioning

confidence: 97%

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confidence: 99%

Conversion of short-term potentiation to long-term potentiation in mouse CA1 by coactivation of β-adrenergic and muscarinic receptors

et al. 2012

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“…A new study in our laboratory has shown that glutamatergic activation of the LC in awake rats produces a delayed ␤-adrenergic receptor-dependent facilitation of both the EPSP slope and population spike amplitude 24 hr after the LC glutamate infusion, an effect that does not require short-term facilitation (Walling and Harley, 2004). Whether orexinergic activation of LC neurons can initiate a similar pattern of synaptic strength changes at 24 hr remains to be examined.…”

Section: Discussionmentioning

confidence: 99%

Orexin-A Infusion in the Locus Ceruleus Triggers Norepinephrine (NE) Release and NE-Induced Long-Term Potentiation in the Dentate Gyrus

Walling¹,

Nutt²,

Lalies³

et al. 2004

J. Neurosci.

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The orexins (ORX-A/ORX-B) are neuroactive peptides known to have roles in feeding and sleep. Evidence of dense, excitatory projections of ORX-A neurons to the noradrenergic pontine nucleus, the locus ceruleus (LC), suggests ORX-A also participates in attention and memory. Activation of LC neurons by glutamate produces a ␤-adrenergic receptor-mediated long-term potentiation (LTP) of the perforant path-evoked potential in the dentate gyrus, a target structure of the LC that has been implicated in memory. We asked whether ORX-A also activates norepinephrine (NE)-induced LTP by initiating NE release in the hippocampus. Here, we show that ORX-A infusion (0.25-25 fmol) into the LC produces a robust, ␤-adrenergic receptor-dependent, long-lasting potentiation of the perforant path-evoked dentate gyrus population spike in the anesthetized rat. Pharmacological inactivation of the LC with an ␣ 2 -adrenergic receptor agonist, before ORX-A infusion, prevents this potentiation. Analysis of NE concentrations in the hippocampus after ORX-A infusion into the LC reveals a transient, but robust, increase in NE release. Thus, this study demonstrates that the dense orexinergic projection to the LC promotes the induction of NE-LTP in the dentate gyrus. ORX-A modulation of LC activity may provide important support for the cognitive processes of attention and memory.

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“…These effects of NA on plasticity in vivo are also mediated by ␤1-adrenoceptors and are probably related to the induction of LTP. Indeed, a recent study in awake rats found that LC stimulation was followed, 24 h later, by protein synthesis-dependent synaptic potentiation in the dentate gyrus (Walling and Harley, 2004). Finally, NA depletion prevents the expression during wakefulness of genes linked to the induction/maintenance of LTP [references in ].…”

Section: Discussionmentioning

confidence: 99%

Locus Ceruleus Control of Slow-Wave Homeostasis

Cirelli¹,

Huber²,

Gopalakrishnan³

et al. 2005

J. Neurosci.

107

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Sleep intensity is regulated by the duration of previous wakefulness, suggesting that waking results in the progressive accumulation of sleep need (Borbély and Achermann, 2000). In mammals, sleep intensity is reflected by slow-wave activity (SWA) in the nonrapid eye movement (NREM) sleep electroencephalogram, which increases in proportion to the time spent awake. However, the mechanisms responsible for the increase of NREM SWA after wakefulness remain unclear. According to a recent hypothesis (Tononi and Cirelli, 2003), the increase in SWA occurs because during wakefulness, many cortical circuits undergo synaptic potentiation, as evidenced by the widespread induction of long-term potentiation (LTP)-related genes in the brain of awake animals. A direct prediction of this hypothesis is that manipulations interfering with the induction of LTP-related genes should result in a blunted SWA response.Here, we examined SWA response in rats in which cortical norepinephrine (NA) was depleted, a manipulation that greatly reduces the induction of LTP-related genes during wakefulness (Cirelli and Tononi, 2004). We found that the homeostatic response of the lower-range SWA was markedly and specifically reduced after NA depletion. These data suggest that the wake-dependent accumulation of sleep need is causally related to cellular changes dependent on NA release, such as the induction of LTP-related genes, and support the hypothesis that sleep SWA homeostasis may be related to synaptic potentiation during wakefulness.

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Locus Ceruleus Activation Initiates Delayed Synaptic Potentiation of Perforant Path Input to the Dentate Gyrus in Awake Rats: A Novel β-Adrenergic- and Protein Synthesis-Dependent Mammalian Plasticity Mechanism

Cited by 103 publications

References 58 publications

Conversion of short-term potentiation to long-term potentiation in mouse CA1 by coactivation of β-adrenergic and muscarinic receptors

Conversion of short-term potentiation to long-term potentiation in mouse CA1 by coactivation of β-adrenergic and muscarinic receptors

Orexin-A Infusion in the Locus Ceruleus Triggers Norepinephrine (NE) Release and NE-Induced Long-Term Potentiation in the Dentate Gyrus

Locus Ceruleus Control of Slow-Wave Homeostasis

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