The Arc of synaptic memory

Bramham, Clive R.; Alme, Maria Nordheim; Bittins, Margarethe; Kuipers, Sjoukje D.; Nair, Rajeevkumar Raveendran; Pai, Balagopal; Panja, Debabrata; Schubert, Manja; Soulé, Jonathan; Tiron, Adrian; Wibrand, Karin

doi:10.1007/s00221-009-1959-2

Cited by 408 publications

(379 citation statements)

References 157 publications

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“…Neural activity-regulated immediate early genes (IEGs), Arc and Egr1, were examined under three experimental conditions: (1) singing and hearing song; (2) hearing song only; and (3) silent controls. Arc is an activity-regulated cytoskeletal-associated protein that acts at recently activated synapses and is involved in the synaptic plasticity of long-term potentiation in mammals 31,32 . In oscines, Arc is upregulated in the nucleus RA by singing, but not hearing of song or under silent conditions 33 .…”

Section: Resultsmentioning

confidence: 99%

Rudimentary substrates for vocal learning in a suboscine

et al. 2013

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Vocal learning has evolved in only a few groups of mammals and birds. The key neuroanatomical and behavioural links bridging vocal learners and non-learners are still unknown. Here we show that a non-vocal-learning suboscine, the eastern phoebe, expresses neural and behavioural substrates that are associated with vocal learning in closely related oscine songbirds. In phoebes, a specialized forebrain region in the intermediate arcopallium seems homologous to the oscine song nucleus RA (robust nucleus of arcopallium) by its neural connections, expression of glutamate receptors and singing-dependent immediate-early gene expression. Lesion of this RA-like region induces subtle but consistent song changes. Moreover, the unlearned phoebe song unexpectedly develops through a protracted ontogeny. These features provide the first evidence of forebrain vocal-motor control in suboscines, which has not been encountered in other avian non-vocal-learners, and offer a potential configuration of brain and behaviour from which vocal learning might have evolved.

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Section: Resultsmentioning

confidence: 99%

Rudimentary substrates for vocal learning in a suboscine

et al. 2013

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“…Through these mechanisms LTP may guide the selective stabilization of synaptic inputs that show coincident activity, whereas nonactivated inputs may be removed and replaced by new spines. Arc is one immediate early gene that may orchestrate the translation of dendritic mRNA required for actin polymerization and stable expansion of dendritic spines during LTP (Bramham et al 2010). Although such structural changes in spines have been studied in some detail, they are not absolutely required for LTP, as synapses made directly on the dendrites (i.e., shaft synapses) are capable of expressing and maintaining LTP.…”

Section: Maintenance Of Ltp and Ltdmentioning

confidence: 99%

NMDA Receptor-Dependent Long-Term Potentiation and Long-Term Depression (LTP/LTD)

Lüscher¹,

Malenka²

2012

Cold Spring Harbor Perspectives in Biology

774

647

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Long-term potentiation and long-term depression (LTP/LTD) can be elicited by activating N-methyl-D-aspartate (NMDA)-type glutamate receptors, typically by the coincident activity of pre-and postsynaptic neurons. The early phases of expression are mediated by a redistribution of AMPA-type glutamate receptors: More receptors are added to potentiate the synapse or receptors are removed to weaken synapses. With time, structural changes become apparent, which in general require the synthesis of new proteins. The investigation of the molecular and cellular mechanisms underlying these forms of synaptic plasticity has received much attention, because NMDA receptor-dependent LTP and LTD may constitute cellular substrates of learning and memory.L ong-term synaptic plasticity is a generic term that applies to a long-lasting experience-dependent change in the efficacy of synaptic transmission. Here we will focus on N-methyl-D-aspartate (NMDA) receptor-dependent synaptic potentiation (LTP) and depression (LTD), two forms of activity-dependent long-term changes in synaptic efficacy that have been extensively studied. Because both LTP and LTD are believed to represent cellular correlates of learning and memory, they have attracted considerable interest. In this article we will focus on the molecular and cellular mechanisms associated with LTP and LTD. As for other forms of long-term synaptic plasticity, a characterization of LTP and LTD involves describing the molecular mechanisms that are required to elicit the change (induction), followed by an investigation of the mechanism of expression (hours) and maintenance (days). The best-characterized form of NMDA receptor (NMDAR)-dependent LTP occurs between CA3 and CA1 pyramidal neurons of the hippocampus (Fig. 1). Throughout the chapter we will mostly refer to this specific form of LTP. At these CA3-CA1 Schaffer collateral synapses, the loci of both induction and expression are situated in the postsynaptic neuron. AMPA-TYPE AND NMDA-TYPE GLUTAMATE RECEPTORSAfter exocytotic release of the content of the synaptic vesicle from the presynaptic specialization (see Castillo 2012), the neurotransmitter

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“…NMDARs are ionotropic glutamate receptors that are prototypical mediators of synaptic plasticity processes involving the induction of plasticity-related genes such as Arc and Zif268 (5,8). We therefore considered the possibility that NMDARs could be potential candidates as mediators of the effects of L-lactate on IEG expression.…”

Section: Significancementioning

confidence: 99%

“…In addition, late response genes such as brain-derived neurotrophic factor (BDNF) have also been demonstrated to be major intermediates of plasticity-related processes (7). A role of NMDA receptors (NMDARs) in such plasticity mechanisms is well-established (5,8).In this article we describe a cascade of molecular events demonstrating that L-lactate stimulates plasticity-related gene expression in neurons through modulation of NMDAR activity associated with changes in redox cellular state. The induction of plasticity gene expression by L-lactate was observed in primary cultures of neurons as well as in vivo in the sensory-motor cortex of mice.…”

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Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons

Yang

Ruchti

Petit

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

373

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L-lactate is a product of aerobic glycolysis that can be used by neurons as an energy substrate. Here we report that in neurons L-lactate stimulates the expression of synaptic plasticity-related genes such as Arc, c-Fos, and Zif268 through a mechanism involving NMDA receptor activity and its downstream signaling cascade Erk1/2. L-lactate potentiates NMDA receptor-mediated currents and the ensuing increase in intracellular calcium. In parallel to this, L-lactate increases intracellular levels of NADH, thereby modulating the redox state of neurons. NADH mimics all of the effects of L-lactate on NMDA signaling, pointing to NADH increase as a primary mediator of L-lactate effects. The induction of plasticity genes is observed both in mouse primary neurons in culture and in vivo in the mouse sensory-motor cortex. These results provide insights for the understanding of the molecular mechanisms underlying the critical role of astrocyte-derived L-lactate in long-term memory and long-term potentiation in vivo. This set of data reveals a previously unidentified action of L-lactate as a signaling molecule for neuronal plasticity.brain energy metabolism | learning and memory | astrocyte-neuron interaction | astrocyte-neuron lactate shuttle T he transfer of L-lactate from astrocytes to neurons was recently shown to be necessary for the establishment of longterm memory (LTM) in an inhibitory avoidance (IA) paradigm and for the maintenance of in vivo long-term potentiation (LTP) in the rodent hippocampus (1). This key role of L-lactate in neuronal plasticity mechanisms was demonstrated in experiments in which specific pharmacological and gene expression down-regulation interventions were implemented to prevent the production of L-lactate from glycogen-which is exclusively localized in astrocytes-and its release from these cells in the hippocampus during behavioral training (1). Such interventions completely prevented the establishment of LTM and their effect was fully reversed by the intrahippocampal administration of L-lactate during the training session. The fact that glucose at equicaloric concentrations only marginally mimicked the rescuing effect of L-lactate was taken as an unexpected indication that the primary mechanism of action of L-lactate on plasticity mechanisms was independent of its ability to act as an energy substrate. A role of L-lactate in memory processes was also recently shown in other behavioral paradigms (2, 3). We therefore set out to investigate the molecular mechanisms at the basis of the function of L-lactate on neuronal plasticity.Molecular mechanisms underlying both LTM and long-term plasticity include the induction of expression of a group of immediate early genes (IEGs) such as early growth response 1 (Zif268 or Egr1), CCAAT/enhancer binding protein (C/EBP), and proto-oncogene c-Fos (c-Fos) as well as activity-regulated cytoskeletal-associated protein (Arc or Arg3.1) as a direct effector protein at the synapse, which all participate to different physiological processes associated with neuronal p...

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The Arc of synaptic memory

Cited by 408 publications

References 157 publications

Rudimentary substrates for vocal learning in a suboscine

Rudimentary substrates for vocal learning in a suboscine

NMDA Receptor-Dependent Long-Term Potentiation and Long-Term Depression (LTP/LTD)

Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons

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