Persistence of Long-Term Memory Storage Requires a Late Protein Synthesis- and BDNF- Dependent Phase in the Hippocampus

Bekinschtein, Pedro; Cammarota, Martı́n; Igaz, Lionel M.; Bevilaqua, Lia R.; Izquierdo, Iván; Medina, Jorge H.

doi:10.1016/j.neuron.2006.11.025

Cited by 570 publications

(556 citation statements)

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“…For instance, the role of de novo protein synthesis and gene expression around training in both structures is critical for memory formation and consolidation (Bekinschtein et al 2007;Alberini 2009), which is in line with correlative studies in humans showing that successful memory formation is associated with an increase in functional connectivity between the hippocampus and some cortical regions, including RSC (Ranganath et al 2005). The timing of some molecular requirements, however, is different for each structure.…”

Section: [Supplemental Materials Is Available For This Article]supporting

confidence: 65%

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Functional integrity of the retrosplenial cortex is essential for rapid consolidation and recall of fear memory

Katche¹,

Dorman²,

Slipczuk

et al. 2013

Learn. Mem.

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Memory storage is a temporally graded process involving different phases and different structures in the mammalian brain. Cortical plasticity is essential to store stable memories, but little is known regarding its involvement in memory processing. Here we show that fear memory consolidation requires early post-training macromolecular synthesis in the anterior part of the retrosplenial cortex (aRSC), and that reversible pharmacological inactivation of this cortical region impairs recall of recent as well as of remote memories. These results challenge the generally accepted idea that neocortical areas are slow encoding systems that participate in the retrieval of remote memories only. [Supplemental material is available for this article.]A dominant idea that emerged in the last two decades is that memory consolidation comprises two phases. The initial one, called cellular or synaptic consolidation, is fast, lasting from several hours to a couple of days, and depends on de novo protein and mRNA synthesis required for functional and structural changes in brain regions engaged in the acquisition and early processing of new information, such as the hippocampus and related noncortical structures (Dudai 2002;Dudai and Eisenberg 2004;Morris 2006). The second phase is slower, and would entail the participation of neocortical regions and their interactions with medial temporal lobe structures reorganizing the recently learned material (Squire 1992). It is called systems-level consolidation and seems to begin late after acquisition and last from several days to weeks to months in most learning tasks studied so far (Frankland and Bontempi 2005). However, when recently encoded information interacts with an already stored associative schema, systems-level consolidation may well be very rapid (Tse et al. 2007(Tse et al. , 2011. Consistent with the standard model of memory consolidation, it has been shown that, while the hippocampus is mainly involved in consolidating and recalling recent episodic-like memories, some cortical regions, including prelimbic, orbitofrontal, and anterior cingulate areas, are involved preferentially with remote, well-consolidated memory traces (Frankland et al. 2004;Maviel et al. 2004;Shan et al. 2008;Lesburgueres et al. 2011;Tse et al. 2011).The retrosplenial cortex (RSC) comprises the entire posterior cingulate cortex in rodents (Vogt and Peters 1981) and is one of the largest cortical areas in the rat. Situated at the crossroads between the hippocampal formation and many neocortical areas, it has attracted much attention especially for its involvement in cognition (Vann et al. 2009). Although RSC inactivation produces memory impairments similar to those caused by hippocampal lesions (Cooper and Mizumori 2001;Vann and Aggleton 2004), and it has been shown that RSC is activated during retrieval of contextual information and autobiographical memory (Valenstein et al. 1987, Daselaar et al. 2006), the precise function of this area is poorly understood (Ranganath and Ritchey 2012).To study the precise r...

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Section: [Supplemental Materials Is Available For This Article]supporting

confidence: 65%

“…Training in this paradigm induces a fear-motivated, hippocampus-dependent, long-lasting memory and permits the uncontaminated analysis of the different stages of memory processing initiated by a single training experience (Izquierdo and Medina 1997;Taubenfeld et al 1999;Bekinschtein et al 2007).…”

Section: [Supplemental Materials Is Available For This Article]mentioning

confidence: 99%

Functional integrity of the retrosplenial cortex is essential for rapid consolidation and recall of fear memory

Katche¹,

Dorman²,

Slipczuk

et al. 2013

Learn. Mem.

Self Cite

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“…Whether this is a consequence of the slower acquisition or the slower acquisition resulted from the lower synaptic BDNF levels cannot be ascertained from the present study. However, a recent report by Bekinschtein et al (2007) suggests that BDNF synthesis in the hippocampus may be necessary for long-term storage of new information. The radial arm maze protocol requires that the rats remember the spatial location of the baited arms (reference memory) across the five days of the task and new BDNF synthesis may be required for this between day retention.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, in the adult animal, BDNF has been implicated in changes in plasticity associated with drug exposure, escalation, and abuse (reviewed by Bolanos and Nestler, 2005; see also Berglind et al, 2007;Cheng et al, 2005;Tsai et al, 2007). Finally, there is a substantial literature documenting the role of BDNF in maintaining synaptic plasticity and modulating learning and memory in adult rats (i.e., Bekinschtein et al, 2007;Hall et al, 2000;Linnarsson et al, 1997;Ma et al, 1998;Mu et al, 1999). The convergence of these factors makes BDNF an attractive target for changes in learning and memory that follow prenatal drug exposure.…”

Section: Introductionmentioning

confidence: 99%

Prenatal opiate exposure impairs radial arm maze performance and reduces levels of BDNF precursor following training

2008

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Prenatal exposure to opiates, which is invariably followed by postnatal withdrawal, can affect cognitive performance. To further characterize these effects, we examined radial 8-arm maze performance and expression of brain derived neurotrophic factor (BDNF) in male rats prenatally exposed to the opiate l-α-acetylmethadol (LAAM). Female rats received 1.0 mg/kg/day LAAM or water via daily oral gavage for 28 days prior to breeding, during breeding, and throughout pregnancy. Pups were fostered to non-treated lactating dams at birth and underwent neonatal opiate withdrawal. At 5-6 months, prenatal water-and LAAM-exposed males (n=6 each; non-littermates) received radial arm maze training consisting of ten trials a day for five days and three retention trials on day six. Rats prenatally exposed to LAAM had poorer maze performance, decreased percent correct responding and more reference and working memory errors than prenatal water-treated controls. However, they were able to acquire the task by the end of training. There were no differences between the groups on retention 24 hr after testing. Following retention testing, hippocampi were removed and protein extracted from cytosol and synaptic fractions. Western blots were used to measure levels of mature and precursor BDNF protein, as well as the BDNF receptor TrkB. BDNF precursor protein was significantly decreased in the synaptic fraction of trained prenatal LAAM-treated rats compared to prenatal water-treated trained controls. No effects were found for the full-length or truncated TrkB receptor. In untrained rats, prenatal treatment did not affect any of the measures. These data suggest that prenatal opiate exposure and/or postnatal withdrawal compromise expression of proteins involved in the neural plasticity underlying learning.

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“…Indeed, environmental enrichment increases hippocampal neurogenesis and survival of newly formed neurons (e.g., Bruel-Jungerman et al 2005), CREB activation (e.g., Williams et al 2001), long-term potentiation (Duffy et al 2001), and brain-derived neurotrophic factor levels (Bakos et al 2009). All these factors contribute to consolidation and thus memory persistence (Bekinschtein et al 2007;Bruel-Jungerman et al 2005;Sekeres et al 2010;Suzuki et al 2011). Interestingly, the capability of enriched environment to enhance long-term memory for object recognition was lost when neurogenesis was blocked (Bruel-Jungerman et al 2005).…”

Section: Spatial Learning and Memorymentioning

confidence: 99%

Lifelong environmental enrichment in rats: impact on emotional behavior, spatial memory vividness, and cholinergic neurons over the lifespan

Harati

Barbelivien

Herbeaux

et al. 2012

AGE

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We assessed lifelong environmental enrichment effects on possible age-related modifications in emotional behaviors, spatial memory acquisition, retrieval of recent and remote spatial memory, and cholinergic forebrain systems. At the age of 1 month, Long-Evans female rats were placed in standard or enriched rearing conditions and tested after 3 (young), 12 (middle-aged), or 24 (aged)months. Environmental enrichment decreased the reactivity to stressful situations regardless of age. In the water maze test, it delayed the onset of learning deficits and prevented age-dependent spatial learning and recent memory retrieval alterations. Remote memory retrieval, which was altered independently of age under standard rearing conditions, was rescued by enrichment in young and middle-aged, but unfortunately not aged rats. A protected basal forebrain cholinergic system, which could well be one out of several neuronal manifestations of lifelong environmental enrichment, might have contributed to the behavioral benefits of this enrichment.

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Persistence of Long-Term Memory Storage Requires a Late Protein Synthesis- and BDNF- Dependent Phase in the Hippocampus

Cited by 570 publications

References 126 publications

Functional integrity of the retrosplenial cortex is essential for rapid consolidation and recall of fear memory

Functional integrity of the retrosplenial cortex is essential for rapid consolidation and recall of fear memory

Prenatal opiate exposure impairs radial arm maze performance and reduces levels of BDNF precursor following training

Lifelong environmental enrichment in rats: impact on emotional behavior, spatial memory vividness, and cholinergic neurons over the lifespan

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