Drug enhancement of memory consolidation: historical perspective and neurobiological implications

McGaugh, James L.; Roozendaal, Benno

doi:10.1007/s00213-008-1285-6

Cited by 215 publications

(146 citation statements)

References 144 publications

(137 reference statements)

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“…18). Thus, it is most likely that the HDAC inhibitor effects on memory are not because of effects on performance, which is a critical factor in studies examining memory enhancements/impairments (22)(23)(24). In a previous study, we showed that the transformation of hippocampal E-LTP into a transcription-dependent form of LTP by HDAC inhibition depended on the interaction between CBP and cyclicAMP response-element binding protein (CREB), a transcription factor (18).…”

Section: Discussionmentioning

confidence: 99%

Modulation of long-term memory for object recognition via HDAC inhibition

Stefanko

Barrett

et al. 2009

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

363

318

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Histone acetylation is a chromatin modification critically involved in gene regulation during many neural processes. The enzymes that regulate levels of histone acetylation are histone acetyltransferases (HATs), which activate gene expression and histone deacetylases (HDACs), that repress gene expression. Acetylation together with other histone and DNA modifications regulate transcription profiles for specific cellular functions. Our previous research has demonstrated a pivotal role for cyclicAMP response element binding protein (CREB)-binding protein (CBP), a histone acetyltransferase, in long-term memory for novel object recognition (NOR). In fact, every genetically modifiedCbp mutant mouse characterized thus far exhibits impaired long-term memory for NOR. These results suggest that long-term memory for NOR is especially sensitive to alterations in CBP activity. Thus, in the current study, we examined the role of HDACs in memory for NOR. We found that inducing a histone hyperacetylated state via HDAC inhibition transforms a learning event that would not normally result in long-term memory into an event that is now remembered long-term. We have also found that HDAC inhibition generates a type of long-term memory that persists beyond a point at which normal memory for NOR fails. This result is particularly interesting because one alluring aspect of examining the role of chromatin modifications in modulating transcription required for long-term memory processes is that these modifications may provide potentially stable epigenetic markers in the service of activating and/or maintaining transcriptional processes.CBP ͉ chromatin ͉ epigenetic ͉ acetylation ͉ CREB

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Section: Discussionmentioning

confidence: 99%

Modulation of long-term memory for object recognition via HDAC inhibition

Stefanko

Barrett

et al. 2009

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

363

318

View full text Add to dashboard Cite

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“…One would therefore need an account with mechanisms that prevent a labile memory from being updated with the new information that occurs during the extinction trial. Some studies suggest that even minimally invasive procedures during periods of memory consolidation can strengthen the fear response (Hui et al 2006), as can other behavioral and pharmacological enhancements of the stress response (McGaugh 2006;McGaugh and Roozendaal 2009). Thus, the simple experience of being returned to a fearful context while the organism is in an aroused state may prevent extinction.…”

Section: Discussionmentioning

confidence: 99%

Exposure to a fearful context during periods of memory plasticity impairs extinction via hyperactivation of frontal-amygdalar circuits

et al. 2013

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An issue of increasing theoretical and translational importance is to understand the conditions under which learned fear can be suppressed, or even eliminated. Basic research has pointed to extinction, in which an organism is exposed to a fearful stimulus (such as a context) in the absence of an expected aversive outcome (such as a shock). This extinction process results in the suppression of fear responses, but is generally thought to leave the original fearful memory intact. Here, we investigate the effects of extinction during periods of memory lability on behavioral responses and on expression of the immediate -early gene c-Fos within fear conditioning and extinction circuits. Our results show that long-term extinction is impaired when it occurs during time periods during which the memory should be most vulnerable to disruption (soon after conditioning or retrieval). These behavioral effects are correlated with hyperactivation of medial prefrontal cortex and amygdala subregions associated with fear expression rather than fear extinction. These findings demonstrate that behavioral experiences during periods of heightened fear prevent extinction and prolong the conditioned fear response.

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“…Nonetheless, effective parameters for other downstream targets may differ. Although a 3-h post-training control experiment was conducted for the inhibition work in order to exclude the possibility that the inhibition was producing longlasting dysfunction in the circuit, we did not perform a similar control with the stimulation experiments, as studies using pharmacological manipulations to produce memory enhancement do not observe effects on retention when given 3 h after training (McGaugh and Roozendaal 2009). Nonetheless, although unlikely, it is possible that the stimulation-induced memory enhancement occurred as a result of effects of the stimulation on performance during the retention test 2 d later, rather than on the memory consolidation.…”

Section: Methodological Considerationsmentioning

confidence: 99%

“…Rats expressing eArchT3.0 received continuous optical inhibition of the BLA VH pathway for 15 min following context or footshock training, with different delays following the training. Because it was possible that the optical manipulations for the inhibition experiments were producing long-lasting dysfunction in the BLA VH circuit that was responsible for the reduced latencies at the retention test, we conducted a control experiment in which the manipulation was given 3 h after training, when the consolidation window is typically observed to be closed (McGaugh and Roozendaal 2009). We did not conduct a similar control experiment with the stimulation study, as it was considered unlikely that dysfunction in the circuit created by stimulation was responsible for the observed increase in latencies at the retention test.…”

Section: Earcht30 Experimentsmentioning

confidence: 99%

“…We did not conduct a similar control experiment with the stimulation study, as it was considered unlikely that dysfunction in the circuit created by stimulation was responsible for the observed increase in latencies at the retention test. Prior studies using pharmacological manipulations to produce memory enhancement have typically not observed effects with 3 h post-training manipulations (LaLumiere et al 2004;McGaugh and Roozendaal 2009) …”

Section: Earcht30 Experimentsmentioning

confidence: 99%

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Basolateral amygdala projections to ventral hippocampus modulate the consolidation of footshock, but not contextual, learning in rats

et al. 2016

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The basolateral amygdala (BLA) modulates memory consolidation for a variety of types of learning, whereas other brain regions play more selective roles in specific kinds of learning suggesting a role for differential consolidation via distinct BLA pathways. The ventral hippocampus (VH), an efferent target of the BLA, has been suggested to selectively process emotionrelated learning, yet whether the BLA VH pathway modulates memory consolidation, and does so in a learning-specific manner, is unknown. To address this issue, the BLA of male Sprague-Dawley rats was bilaterally transduced to express either ChR2(E123A) or eArchT3.0. Fiber optic probes were implanted in the VH to provide illumination of BLA axons. Rats then underwent a modified contextual fear conditioning task permitting separation of context and footshock learning. On day 1, rats received 3 min of pre-exposure to the apparatus. On day 2, rats were placed into the apparatus, received an immediate footshock, and quickly removed. Retention was tested on day 4. Optical stimulation of the BLA VH pathway following footshock, but not context, training using trains of 40-Hz light pulses enhanced retention. Continuous optical inhibition of this pathway for 15 min starting 25 min after footshock training impaired retention. These findings indicate that BLA VH projections influence the consolidation for footshock, but not context, learning of a modified CFC task and provide direct evidence that BLA projections to other brain regions modulate memory consolidation selectively depending on the kind of learning involved.Learning and memory involves complex interactions among multiple brain regions that play discrete roles in the consolidation of specific kinds of memories. However, work strongly indicates that the basolateral amygdala (BLA) modulates the consolidation of a wide array of memories. It has been hypothesized that the BLA plays this more general role, at least in part, through interactions with distinct regions (McGaugh 2002(McGaugh , 2004McIntyre et al. 2012). BLA connections with forebrain regions such as the hippocampus and striatum that are selectively involved in the consolidation of certain kinds of memories (McDonald 1991;Pitkänen et al. 2000;McGaugh 2002;Malin and McGaugh 2006;Paz et al. 2006;Chavez et al. 2013) suggest that efferent pathways from the BLA may be selectively involved in modulating consolidation for specific kinds of information.Indeed, much evidence suggests that the BLA interacts with the hippocampus during memory consolidation (Packard et al. 1994;Roozendaal et al. 1999;Malin and McGaugh 2006) and that the BLA directly or indirectly influences activity and plasticity in different parts of the hippocampal formation (Ikegaya et al. 1995;Frey et al. 2001;McIntyre et al. 2005;McReynolds et al. 2014;Lovitz and Thompson 2015). These findings suggest pathway mechanisms by which the BLA influences the consolidation of memories regulated by the hippocampal formation. However, the hippocampus comprises different subregions, including dors...

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Drug enhancement of memory consolidation: historical perspective and neurobiological implications

Cited by 215 publications

References 144 publications

Modulation of long-term memory for object recognition via HDAC inhibition

Modulation of long-term memory for object recognition via HDAC inhibition

Exposure to a fearful context during periods of memory plasticity impairs extinction via hyperactivation of frontal-amygdalar circuits

Basolateral amygdala projections to ventral hippocampus modulate the consolidation of footshock, but not contextual, learning in rats

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