Regulation Of Memory Consolidation Research Articles

Connecting the Dots: Potential Interactions Between Sex Hormones and the Circadian System During Memory Consolidation.

Both the circadian clock and sex hormone signaling can strongly influence brain function, yet little is known about how these 2 powerful modulatory systems might interact during complex neural processes like memory consolidation. Individually, the molecular components and action of each of these systems have been fairly well-characterized, but there is a fundamental lack of information about how these systems cooperate. In the circadian system, clock genes function as timekeeping molecules that convey time-of-day information on a well-stereotyped cycle that is governed by the suprachiasmatic nucleus. Keeping time is particularly important to synchronize various physiological processes across the brain and body, including those that regulate memory consolidation. Similarly, sex hormones are powerful modulators of memory, with androgens, estrogens, and progestins, all influencing memory consolidation within memory-relevant brain regions like the hippocampus. Despite clear evidence that each system can influence memory individually, exactly how the circadian and hormonal systems might interact to impact memory consolidation remains unclear. Research investigating either sex hormone action or circadian gene function within memory-relevant brain regions has unveiled several notable places in which the two systems could interact to control memory. Here, we bring attention to known interactions between the circadian clock and sex hormone signaling. We then review sex hormone-mediated control of memory consolidation, highlighting potential nodes through which the circadian system might interact during memory formation. We suggest that the bidirectional relationship between these two systems is essential for proper control of memory formation based on an animal's hormonal and circadian state.

Norepinephrine Regulates Spatial Memory Consolidation Using Barnes Maze in Male, but Not Female Rats (P1-12.009)

<h3>Objective:</h3> Here, we study the role of NE on spatial learning and memory in rats using a Barnes maze assay. <h3>Background:</h3> The role of norepinephrine (NE) in learning and memory has been extensively studied, yet its contribution to different phases of memory, such as consolidation or updating, remains elusive. <h3>Design/Methods:</h3> We used a specific noradrenergic neurotoxin (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4)) to deplete central NE stores. In experiment one, Wistar rats (n=16/sex) were trained to reach a hidden goal box using visual and auditory cues for five days with three trials per day. Rats were administered 50 mg/kg/i.p of DSP-4 or saline ten days prior to training on the Barnes maze assay. DSP-4 mediated reduction of NE, but not serotonin or dopamine, was confirmed using HPLC in several brain regions. In experiment two, using female and male rats (n=16/sex), we replicated results of experiment one by utilizing two trials per day to increase the difficulty of learning the task and extended the findings by utilizing a single probe trial (memory consolidation) and a two-day reversal (memory updating) learning task. <h3>Results:</h3> In experiment one, female and male rats in DSP-4 and saline groups learned the location of the hidden zone, and this was measured by a reduction in latency to reach the goal box. Levels of NE were significantly lower in the dorsal hippocampus, cingulate cortex, and the striatum. Experiment two replicated these results and the subsequent behavioral analysis suggests that only male DSP-4 treated rats increased time spent in the covered hidden zone area during the probe trial. During the reversal learning task, DSP-4 treated males continued to visit the previously hidden platform despite learning the new goal location. <h3>Conclusions:</h3> These data suggest that NE plays a role in regulation of memory consolidation rather than acquisition or memory updating, and this regulation may be sex-specific. <b>Disclosure:</b> Ms. Simpson has nothing to disclose. Dr. Gheidi has nothing to disclose. Dr. Davidson has nothing to disclose. Mr. Yahya has nothing to disclose. Mrs. Trombley has nothing to disclose. Miss Sadik has received personal compensation for serving as an employee of Wayne State University . The institution of Dr. Perrine has received research support from NIH.

Small-molecule screening in aged Drosophila identifies mGluR as a regulator of age-related sleep impairment.

As a normal physiological phenomenon, aging has a significant impact on sleep. Aging leads to sleep impairment, including sleep loss, fragmented sleep, and a lower arousal threshold, leading to various diseases. Because sleep regulates memory consolidation, age-dependent sleep impairment also affects memory. However, the mechanisms underlying age-related sleep dysregulation and its impact on memory remain unclear. Using male and female Drosophila as a model, which possesses sleep characteristics similar to those of mammals and exhibits age-dependent sleep impairment, we performed small-molecule screening to identify novel regulators of age-dependent decline in sleep. The screening identified 3,3'-difluorobenzaldazine (DFB), a positive allosteric modulator of the metabotropic glutamate receptor (mGluR) 5, as a novel sleep-promoting compound in aged flies. We found that mutant flies of mGluR, a single mGluR gene in Drosophila, and decreased mGluR expression had significant impairment in sleep and memory due to olfactory conditioning. The decreased sleep phenotype in the mGluR mutants was not promoted by DFB, suggesting that the effects of DFB on age-dependent sleep impairment are dependent on mGluR. Although aging decreases the expression of mGluR and the binding scaffold proteins Homer and Shank, the transient overexpression of mGluR in neurons improves sleep in both young and aged flies. Overall, these findings indicate that age-dependent decreased expression or function of mGluR impairs sleep and memory in flies, which could lead to age-related sleep and memory impairment.

Application of a pharmacological transcriptome filter identifies a shortlist of mouse glucocorticoid receptor target genes associated with memory consolidation

Glucocorticoids regulate memory consolidation, facilitating long-term storage of relevant information to adequately respond to future stressors in similar conditions. This effect of glucocorticoids is well-established and is observed in multiple types of behaviour that depend on various brain regions. By and large, higher glucocorticoid levels strengthen event-related memory, while inhibition of glucocorticoid signalling impairs consolidation. The mechanism underlying this glucocorticoid effect remains unclear, but it likely involves the transcriptional effects of the glucocorticoid receptor (GR). We here used a powerful paradigm to investigate the transcriptional effects of GR in the dorsal hippocampus of mice after training in an auditory fear conditioning task, aiming to identify a shortlist of GR target genes associated to memory consolidation. Therefore, we utilized in an explorative study the properties of selective GR modulators (CORT108297 and CORT118335), alongside the endogenous agonist corticosterone and the classical GR antagonist RU486, to pinpoint GR-dependent transcriptional changes. First, we confirmed that glucocorticoids can modulate memory strength via GR activation. Subsequently, by assessing the specific effects of the available GR-ligands on memory strength, we established a pharmacological filter which we imposed on the hippocampal transcriptome data. This identified a manageable shortlist of eight genes by which glucocorticoids may modulate memory consolidation, warranting in-depth follow-up. Overall, we showcase the strength of the concept of pharmacological transcriptome filtering, which can be readily applied to other research topics with an established role of glucocorticoids.

Long-term potentiation at pyramidal cell to somatostatin interneuron synapses controls hippocampal network plasticity and memory

SummaryHippocampal somatostatin (SOM) cells are dendrite-projecting inhibitory interneurons. CA1 SOM cells receive major excitatory inputs from pyramidal cells (PC-SOM synapses) which show mGluR1a- and mTORC1-mediated long-term potentiation (LTP). PC-SOM synapse LTP contributes to CA1 network metaplasticity and memory consolidation, but whether it is sufficient to regulate these processes remains unknown. Here we used optogenetic stimulation of CA1 pyramidal cells and whole-cell recordings in slices to show that optogenetic theta-burst stimulation (TBSopto) produces LTP at PC-SOM synapses. At the network level, we found that TBSopto differentially regulates metaplasticity of pyramidal cell inputs: enhancing LTP at Schaffer collateral synapses and depressing LTP at temporo-ammonic synapses. At the behavioral level, we uncovered that in vivo TBSopto regulates learning-induced LTP at PC-SOM synapses, as well as contextual fear memory. Thus, LTP of PC-SOM synapses is a long-term feedback mechanism controlling pyramidal cell synaptic plasticity, sufficient to regulate memory consolidation.

Rhythmic Memory Consolidation in the Hippocampus.

Functions of the brain and body are oscillatory in nature and organized according to a logarithmic scale. Brain oscillations and bodily functions such as respiration and heartbeat appear nested within each other and coupled together either based on phase or based on phase and amplitude. This facilitates communication in wide-spread neuronal networks and probably also between the body and the brain. It is a widely accepted view, that nested electrophysiological brain oscillations involving the neocortex, thalamus, and the hippocampus form the basis of memory consolidation. This applies especially to declarative memories, that is, memories of life events, for example. Here, we present our view of hippocampal contribution to the process of memory consolidation based on the general ideas stated above and on some recent findings on the topic by us and by other research groups. We propose that in addition to the interplay between neocortical slow oscillations, spindles, and hippocampal sharp-wave ripples during sleep, there are also additional mechanisms available in the hippocampus to control memory consolidation: a rather non-oscillatory hippocampal electrophysiological phenomenon called the dentate spike might provide a means to not only consolidate but to also modify the neural representation of declarative memories. Further, we suggest that memory consolidation in the hippocampus might be in part paced by breathing. These considerations might open new possibilities for regulating memory consolidation in rest and sleep.

Neuropeptide F inhibits dopamine neuron interference of long-term memory consolidation in Drosophila

Long-term memory (LTM) formation requires consolidation processes to overcome interfering signals that erode memory formation. Olfactory memory in Drosophila involves convergent projection neuron (PN; odor) and dopaminergic neuron (DAN; reinforcement) input to the mushroom body (MB). How post-training DAN activity in the posterior lateral protocerebrum (PPL1) continues to regulate memory consolidation remains unknown. Here we address this question using targeted transgenes in behavior and electrophysiology experiments to show that (1) persistent post-training activity of PPL1-α2α'2 and PPL1-α3 DANs interferes with aversive LTM formation; (2) neuropeptide F (NPF) signaling blocks this interference in PPL1-α2α'2 and PPL1-α3 DANs after spaced training to enable LTM formation; and (3) training-induced NPF release and neurotransmission from two upstream dorsal-anterior-lateral (DAL2) neurons are required to form LTM. Thus, NPF signals from DAL2 neurons to specific PPL1 DANs disinhibit the memory circuit, ensuring that periodic events are remembered as consolidated LTM.

Initiated by CREB: Resolving Gene Regulatory Programs in Learning and Memory: Switch in Cofactors and Transcription Regulators between Memory Consolidation and Maintenance Network.

Consolidation of long-term memory is a highly and precisely regulated multistep process. The transcription regulator cAMP response element-binding protein (CREB) plays a key role in initiating memory consolidation. With time processing, first the cofactors are changed and, secondly, CREB gets dispensable. This ultimately changes the expressed gene program to genes required to maintain the memory. Regulation of memory consolidation also requires epigenetic mechanisms and control at the RNA level. At the neuronal circuit level, oscillation in the activity of CREB and downstream factor define engram cells. Together the combination of all regulation mechanisms allows correct memory processing while keeping the process dynamic and flexible to adjust to different contexts. Also see the video abstract here https://youtu.be/BhSCSmorpEc.

Neuropeptide VGF C-Terminal Peptide TLQP-62 Alleviates Lipopolysaccharide-Induced Memory Deficits and Anxiety-like and Depression-like Behaviors in Mice: The Role of BDNF/TrkB Signaling.

Peripheral inflammatory responses affect central nervous system (CNS) function, manifesting in symptoms of memory deficits, depression, and anxiety. Previous studies have revealed that neuropeptide VGF (nonacronymic) C-terminal peptide TLQP-62 rapidly reinforces brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling, regulating memory consolidation and antidepressant-like action. However, whether it is beneficial for lipopolysaccharide (LPS)-induced neuropsychiatric dysfunction in mice is unknown. Herein, we explored the involvement of BDNF/TrkB signaling and biochemical alterations in inflammatory or oxidative stress markers in the alleviating effects of TLQP-62 on LPS-induced neuropsychiatric dysfunction. The mice were treated with TLQP-62 (2 μg/side) via intracerebroventricular (i.c.v.) injection 1 h before LPS (0.5 mg/kg, i.p.) administration. Our results showed that a single treatment with LPS (0.5 mg/kg, i.p) is sufficient to produce recognition memory deficits (in the novel object recognition test), depression-like behavior (in the forced swim test and sucrose preference test), and anxiety-like behavior (in the elevated zero maze). However, pretreatment with TLQP-62 prevented LPS-induced behavioral dysfunction, neuroinflammatory, and oxidative responses. In addition, our results further demonstrated that a reduction in BDNF expression mediated by BDNF-shRNA lentivirus significantly blocked the effects of TLQP-62, suggesting the critical role of BDNF/TrkB signaling in the neuroprotective effects of TLQP-62 in the mice. In conclusion, TLQP-62 could be a therapeutic approach for neuropsychiatric disorders, which are closely associated with neuroinflammation and oxidative stress.

β1-and β2-adrenoceptors in hippocampal CA3 region are required for long-term memory consolidation in rats

The existence of β-adrenoceptors (ARs) in the hippocampus and the importance of β-ARs in regulating synaptic plasticity and learning/memory function are well documented. As known, β-ARs in area cornu ammonis 1 (CA1) are involved in regulating memory consolidation. However, little is known about the functional roles of the β-ARs subtypes, β1- and β2-ARs, in the hippocampal cornu ammonis 3 (CA3) region. To address this question, we firstly locally infused the β1- or β2-ARs antagonist into the CA3 region and observed that blockage of either β1-AR or β2-AR impaired long-term contextual fear memory and water-maze spatial memory. We also found that, following the contextual fear conditioning, the expression of β1-AR in the CA3 region significantly increased, whereas β2-AR was unchanged. Then intra-CA3 infusion of recombinant lentiviral RNAi vectors for β1 or β2-ARs also produced deficit in contextual memory consolidation. Taken together, the results suggested that the β1- and β2-ARs in the CA3 region were involved in hippocampus dependent memory consolidation.

Nuclear Arc Interacts with the Histone Acetyltransferase Tip60 to Modify H4K12 Acetylation(1,2,3).

Arc is an immediate-early gene whose genetic ablation selectively abrogates long-term memory, indicating a critical role in memory consolidation. Although Arc protein is found at synapses, it also localizes to the neuronal nucleus, where its function is less understood. Nuclear Arc forms a complex with the β-spectrin isoform βSpIVΣ5 and associates with PML bodies, sites of epigenetic regulation of gene expression. We report here a novel interaction between Arc and Tip60, a histone-acetyltransferase and subunit of a chromatin-remodelling complex, using biochemistry and super-resolution microscopy in primary rat hippocampal neurons. Arc and βSpIVΣ5 are recruited to nuclear Tip60 speckles, and the three proteins form a tight complex that localizes to nuclear perichromatin regions, sites of transcriptional activity. Neuronal activity-induced expression of Arc (1) increases endogenous nuclear Tip60 puncta, (2) recruits Tip60 to PML bodies, and (3) increases histone acetylation of Tip60 substrate H4K12, a learning-induced chromatin modification. These mechanisms point to an epigenetic role for Arc in regulating memory consolidation.

Histamine acting on the basolateral amygdala reverts the impairment of aversive memory of rats submitted to neonatal maternal deprivation

Recent findings suggest a role of brain histamine in the regulation of memory consolidation, particularly in one-trial inhibitory avoidance (IA) learning and that disruption in the mother infant relationship i.e. maternal deprivation induces cognitive deficits. We investigate whether histamine itself, and histaminergic compounds given into the basolateral amygdala (BLA) immediately post-training can affect retention (24h after training) of one-trial (IA) in rats submitted to early postnatal maternal deprivation. In all cases, deprived (Dep) animals had lower retention scores than non-deprived controls (N-dep). Histamine induced memory enhancement on its own in N-dep animals and was able to overcome the deleterious effect of Dep. The effects by SKF-91488 is similar to histamine. The H3 agonist, imetit mimetized the enhancing effects of histamine; neither agonist H1 pyridylethylamine nor the H2 dimaprit had any effect. Ranitidine and thioperamide (50nmol) co-infused with histamine (10nmol) fully blocked the restorative effect of histamine on retention in Dep animals. Thioperamide, in addition, blocked the enhancing effect of histamine on memory of the N-dep animals as well. None of the drugs used given into BLA had any effect on open-field or elevated plus-maze behavior in N-dep or Dep rats. Our results are limited to experimental design in rats. Extrapolation i.e. in humans requires further experimentations. The present results suggest that the memory deficit induced by early postnatal maternal deprivation in rats may at least in part be due to an impairment of histamine H3 receptor-mediated mediated mechanisms in the BLA.

Glia Protein Aquaporin‐4 Regulates Aversive Motivation of Spatial Memory in Morris Water Maze

Although extensive investigation has revealed that an astrocyte-specific protein aquaporin-4 (AQP4) participates in regulating synaptic plasticity and memory, a functional relationship between AQP4 and learning processing has not been clearly established. This study was designed to test our hypothesis that AQP4 modulates the aversive motivation in Morris water maze (MWM). Using hidden platform training, we observed that AQP4 KO mice significantly decreased their swimming velocity compared with wild-type (WT) mice. To test for a relationship between velocities and escape motivation, we removed the platform and subjected a new group of mice similar to the session of hidden platform training. We found that KO mice exhibited a gradual reduction in swimming velocity, while WT mice did not alter their velocity. In the subsequent probe trial, KO mice after no platform training significantly decreased their mean velocity compared with those KO mice after hide platform training. However, all of KO mice were not impaired in their ability to locate a visible, cued escape platform. Our findings, along with a previous report that AQP4 regulates memory consolidation, implicate a novel role for this glial protein in modulating the aversive motivation in spatial learning paradigm.

The Cell and Molecular Biology of Neurodegenerative Diseases: An Overview

The Cell and Molecular Biology of Neurodegenerative Diseases: An Overview

A New Player in the “Synaptopathy” of Alzheimer’s Disease – Arc/Arg 3.1

Alzheimer’s disease (AD) is increasingly referred to as a “synaptopathy.” This moniker reflects the loss or damage of synapses that occurs as the disease progresses, which in turn produces functional degeneration of specific neuronal circuits and consequent aberrant activity in neural networks. Accumulating evidence supports the functional importance of the early-expression activity-regulated cytoskeletal (Arc) gene in regulating memory consolidation. Interestingly, AD patients express anomalously high levels of Arc protein. Arc physically associates with presenilin1, a pivotal protease for the generation of Amyloid β (Aβ) peptides. Arc expression itself is disrupted in the vicinity of Aβ oligomers and plaques. Such alterations result in the interruption of neuronal network integration in vivo. It is not clear what the impacts of these alterations are on the functional neurophysiology of transgenic mouse models of AD-associated amyloidopathy. Our group and others have described alterations to neuronal excitability and thus intrinsic firing within these transgenic mice models. This brief review will emphasize the rising role of Arc and its involvement in neurophysiological alterations of current AD models.

Memory modulation.

Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive evidence from both animal and human research indicates that emotionally significant experiences activate hormonal and brain systems that regulate the consolidation of newly acquired memories. These effects are integrated through noradrenergic activation of the basolateral amygdala that regulates memory consolidation via interactions with many other brain regions involved in consolidating memories of recent experiences. Modulatory systems not only influence neurobiological processes underlying the consolidation of new information, but also affect other mnemonic processes, including memory extinction, memory recall, and working memory. In contrast to their enhancing effects on consolidation, adrenal stress hormones impair memory retrieval and working memory. Such effects, as with memory consolidation, require noradrenergic activation of the basolateral amygdala and interactions with other brain regions.

Upregulation of CREB-Mediated Transcription Enhances Both Short- and Long-Term Memory

Unraveling the mechanisms by which the molecular manipulation of genes of interest enhances cognitive function is important to establish genetic therapies for cognitive disorders. Although CREB is thought to positively regulate formation of long-term memory (LTM), gain-of-function effects of CREB remain poorly understood, especially at the behavioral level. To address this, we generated four lines of transgenic mice expressing dominant active CREB mutants (CREB-Y134F or CREB-DIEDML) in the forebrain that exhibited moderate upregulation of CREB activity. These transgenic lines improved not only LTM but also long-lasting long-term potentiation in the CA1 area in the hippocampus. However, we also observed enhanced short-term memory (STM) in contextual fear-conditioning and social recognition tasks. Enhanced LTM and STM could be dissociated behaviorally in these four lines of transgenic mice, suggesting that the underlying mechanism for enhanced STM and LTM are distinct. LTM enhancement seems to be attributable to the improvement of memory consolidation by the upregulation of CREB transcriptional activity, whereas higher basal levels of BDNF, a CREB target gene, predicted enhanced shorter-term memory. The importance of BDNF in STM was verified by microinfusing BDNF or BDNF inhibitors into the hippocampus of wild-type or transgenic mice. Additionally, increasing BDNF further enhanced LTM in one of the lines of transgenic mice that displayed a normal BDNF level but enhanced LTM, suggesting that upregulation of BDNF and CREB activity cooperatively enhances LTM formation. Our findings suggest that CREB positively regulates memory consolidation and affects memory performance by regulating BDNF expression.

Propofol Enhances Memory Formation via an Interaction with the Endocannabinoid System

Propofol is associated with postoperative mood alterations and induces a higher incidence of dreaming compared with other general anesthetics. These effects might be mediated by propofol's inhibitory action on fatty acid amide hydrolase, the enzyme that degrades the endocannabinoid anandamide. Because propofol is also associated with a higher incidence of traumatic memories from perioperative awareness and intensive care unit treatment and the endocannabinoid system is involved in regulating memory consolidation of emotional experiences, the authors investigated whether propofol, at anesthetic doses, modulates memory consolidation via an activation of the endocannabinoid system. Male Sprague-Dawley rats were trained on an inhibitory avoidance task in which they received an inescapable foot shock upon entering the dark compartment of the apparatus. Drugs were administered intraperitoneally immediately or 30, 90, or 180 min after training. On the retention test 48 h later, the latency to reenter the dark compartment was recorded and taken as a measure of memory retention. The anesthetic doses of propofol administered after training significantly increased latencies of 48-h inhibitory avoidance performance (483.4 ± 181.3, 432.89 ± 214.06, 300 and 350 mg/kg, respectively; mean ± SD) compared with the corresponding vehicle group (325.33 ± 221.22, mean ± SD), which is indicative of stronger memory consolidation in propofol treated rats. Administration of a nonimpairing dose of the cannabinoid receptor antagonist rimonabant blocked the memory enhancement induced by propofol (123.39 ± 133.10, mean ± SD). Delayed administration of propofol 90 and 180 min after training or immediate posttraining administration of the benzodiazepine midazolam or the barbiturate pentobarbital did not significantly alter retention. These findings indicate that propofol, in contrast to other commonly used sedatives, enhances emotional memory consolidation when administered immediately after a stressful event by enhancing endocannabinoid signaling.

Epigenetic Alterations Are Critical for Fear Memory Consolidation and Synaptic Plasticity in the Lateral Amygdala

Epigenetic mechanisms, including histone acetylation and DNA methylation, have been widely implicated in hippocampal-dependent learning paradigms. Here, we have examined the role of epigenetic alterations in amygdala-dependent auditory Pavlovian fear conditioning and associated synaptic plasticity in the lateral nucleus of the amygdala (LA) in the rat. Using Western blotting, we first show that auditory fear conditioning is associated with an increase in histone H3 acetylation and DNMT3A expression in the LA, and that training-related alterations in histone acetylation and DNMT3A expression in the LA are downstream of ERK/MAPK signaling. Next, we show that intra-LA infusion of the histone deacetylase (HDAC) inhibitor TSA increases H3 acetylation and enhances fear memory consolidation; that is, long-term memory (LTM) is enhanced, while short-term memory (STM) is unaffected. Conversely, intra-LA infusion of the DNA methyltransferase (DNMT) inhibitor 5-AZA impairs fear memory consolidation. Further, intra-LA infusion of 5-AZA was observed to impair training-related increases in H3 acetylation, and pre-treatment with TSA was observed to rescue the memory consolidation deficit induced by 5-AZA. In our final series of experiments, we show that bath application of either 5-AZA or TSA to amygdala slices results in significant impairment or enhancement, respectively, of long-term potentiation (LTP) at both thalamic and cortical inputs to the LA. Further, the deficit in LTP following treatment with 5-AZA was observed to be rescued at both inputs by co-application of TSA. Collectively, these findings provide strong support that histone acetylation and DNA methylation work in concert to regulate memory consolidation of auditory fear conditioning and associated synaptic plasticity in the LA.

Fatty-Acid Binding Proteins Modulate Sleep and Enhance Long-Term Memory Consolidation in Drosophila

Sleep is thought to be important for memory consolidation, since sleep deprivation has been shown to interfere with memory processing. However, the effects of augmenting sleep on memory formation are not well known, and testing the role of sleep in memory enhancement has been limited to pharmacological and behavioral approaches. Here we test the effect of overexpressing the brain-type fatty acid binding protein (Fabp7) on sleep and long-term memory (LTM) formation in Drosophila melanogaster. Transgenic flies carrying the murine Fabp7 or the Drosophila homologue dFabp had reduced baseline sleep but normal LTM, while Fabp induction produced increases in both net sleep and LTM. We also define a post-training consolidation “window” that is sufficient for the observed Fabp-mediated memory enhancement. Since Fabp overexpression increases consolidated daytime sleep bouts, these data support a role for longer naps in improving memory and provide a novel role for lipid-binding proteins in regulating memory consolidation concurrently with changes in behavioral state.