Neurotensin orchestrates valence assignment in the amygdala.

The ability to associate temporally segregated information and assign positive or negative valence to environmental cues is paramount for survival. Studies have shown that different projections from the basolateral amygdala (BLA) are potentiated following reward or punishment learning1-7. However, we do not yet understand how valence-specific information is routed to the BLA neurons with the appropriate downstream projections, nor do we understand how to reconcile the sub-second timescales of synaptic plasticity8-11 with the longer timescales separating the predictive cues from their outcomes. Here we demonstrate that neurotensin (NT)-expressing neurons in the paraventricular nucleus of the thalamus (PVT) projecting to the BLA (PVT-BLA:NT) mediate valence assignment by exerting NT concentration-dependent modulation in BLA during associative learning. We found that optogenetic activation of the PVT-BLA:NT projection promotes reward learning, whereas PVT-BLA projection-specific knockout of the NT gene (Nts) augments punishment learning. Using genetically encoded calcium and NT sensors, we further revealed that both calcium dynamics within the PVT-BLA:NT projection and NT concentrations in the BLA are enhanced after reward learning and reduced after punishment learning. Finally, we showed that CRISPR-mediated knockout of the Nts gene in the PVT-BLA pathway blunts BLA neural dynamics and attenuates the preference for active behavioural strategies to reward and punishment predictive cues. In sum, we have identified NT as a neuropeptide that signals valence in the BLA, and showed that NT is a critical neuromodulator that orchestrates positive and negative valence assignment in amygdala neurons by extending valence-specific plasticity to behaviourally relevant timescales.

LIMK, Cofilin 1 and actin dynamics involvement in fear memory processing.

Long-term memory has been associated with morphological changes in the brain, which in turn tightly correlate with changes in synaptic efficacy. Such plasticity is proposed to rely on dendritic spines as a neuronal canvas on which these changes can occur. Given the key role of actin cytoskeleton dynamics in spine morphology, major regulating factors of this process such as Cofilin 1 (Cfl1) and LIM kinase (LIMK), an inhibitor of Cfl1 activity, are prime molecular targets that may regulate dendritic plasticity. Using a contextual fear conditioning paradigm in mice, we found that pharmacological induction of depolymerization of actin filaments through the inhibition of LIMK causes an impairment in memory reconsolidation, as well as in memory consolidation. On top of that, Cfl1 activity is inhibited and its mRNA is downregulated in CA1 neuropil after re-exposure to the training context. Moreover, by pharmacological disruption of actin cytoskeleton dynamics, the process of memory extinction can either be facilitated or impaired. Our results lead to a better understanding of the role of LIMK, Cfl1 and actin cytoskeleton dynamics in the morphological and functional changes underlying the synaptic plasticity of the memory trace.

Differential expression analysis for subolesin in Rhipicephalus microplus infected with Anaplasma marginale.

Rhipicephalus microplus (formerly Boophilus microplus) ticks are potential vectors of several pathogens of livestock especially in tropical and subtropical regions where may have substantial effects on economic development. Among tick-borne pathogens, Anaplasma marginale is considered one of the most important in domestic and wild ruminants worldwide. Different molecular mechanisms have been employed by both ticks and these intracellular pathogens, in order to be able to adapt and survive. Subolesin, originally called 4D8, is an evolutionarily well-preserved protein among ixodid tick species. This new antigen was found to be protective against tick infestations when used as a vaccine, as it has an essential role in tick blood digestion, development and infection of host cells by A. marginale. Recent studies have demonstrated that infection of both tick and vertebrate host cells with this microorganism changed gene expression. Therefore, the main objective of this study was to investigate subolesin expression in uninfected and A. marginale-infected R. microplus salivary glands by real-time reverse transcriptase (RT)-PCR. To analyze the differential expression of the recombinant protein subolesin, the gene was previously expressed from ticks infected with A. marginale. Results from this study revealed that, the expression of subolesin was significantly higher in salivary glands of infected R. microplus in comparison to uninfected ones.

CDK5-mediated phosphorylation of p19INK4d avoids DNA damage-induced neurodegeneration in mouse hippocampus and prevents loss of cognitive functions.

DNA damage, which perturbs genomic stability, has been linked to cognitive decline in the aging human brain, and mutations in DNA repair genes have neurological implications. Several studies have suggested that DNA damage is also increased in brain disorders such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. However, the precise mechanisms connecting DNA damage with neurodegeneration remain poorly understood. CDK5, a critical enzyme in the development of the central nervous system, phosphorylates a number of synaptic proteins and regulates dendritic spine morphogenesis, synaptic plasticity and learning. In addition to these physiological roles, CDK5 has been involved in the neuronal death initiated by DNA damage. We hypothesized that p19INK4d, a member of the cell cycle inhibitor family INK4, is involved in a neuroprotective mechanism activated in response to DNA damage. We found that in response to genotoxic injury or increased levels of intracellular calcium, p19INK4d is transcriptionally induced and phosphorylated by CDK5 which provides it with greater stability in postmitotic neurons. p19INK4d expression improves DNA repair, decreases apoptosis and increases neuronal survival under conditions of genotoxic stress. Our in vivo experiments showed that decreased levels of p19INK4d rendered hippocampal neurons more sensitive to genotoxic insult resulting in the loss of cognitive abilities that rely on the integrity of this brain structure. We propose a feedback mechanism by which the neurotoxic effects of CDK5-p25 activated by genotoxic stress or abnormal intracellular calcium levels are counteracted by the induction and stabilization of p19INK4d protein reducing the adverse consequences on brain functions.

Nuclear factor kappa B-dependent Zif268 expression in hippocampus is required for recognition memory in mice.

Long-term memory formation requires gene expression after acquisition of new information. The first step in the regulation of gene expression is the participation of transcription factors (TFs) such as nuclear factor kappa B (NF-кB), which are present before the neuronal activity induced by training. It was proposed that the activation of these types of TFs allows a second step in gene regulation by induction of immediate-early genes (IEGs) whose protein products are, in turn, TFs. Between these IEGs, zif268 has been found to play a critical role in long-term memory formation and reprocessing after retrieval. Here we found in mice hippocampus that, on one hand, NF-кB was activated 45 min after training in a novel object recognition (NOR) task and that inhibiting NF-кB immediately after training by intrahippocampal administration of NF-кB Decoy DNA impaired NOR memory consolidation. On the other hand, Zif268 protein expression was induced 45 min after NOR training and the administration of DNA antisense to its mRNA post-training impaired recognition memory. Finally, we found that the inhibition of NF-кB by NF-кB Decoy DNA reduced significantly the training-induced Zif268 increment, indicating that NF-кB is involved in the regulation of Zif268 expression. Thus, the present results support the involvement of NF-кB activity-dependent Zif268 expression in the hippocampus during recognition memory consolidation.

Protein degradation by ubiquitin-proteasome system in formation and labilization of contextual conditioning memory.

The ubiquitin-proteasome system (UPS) of protein degradation has been evaluated in different forms of neural plasticity and memory. The role of UPS in such processes is controversial. Several results support the idea that the activation of this system in memory consolidation is necessary to overcome negative constrains for plasticity. In this case, the inhibition of the UPS during consolidation impairs memory. Similar results were reported for memory reconsolidation. However, in other cases, the inhibition of UPS had no effect on memory consolidation and reconsolidation but impedes the amnesic action of protein synthesis inhibition after retrieval. The last finding suggests a specific action of the UPS inhibitor on memory labilization. However, another interpretation is possible in terms of the synthesis/degradation balance of positive and negative elements in neural plasticity, as was found in the case of long-term potentiation. To evaluate these alternative interpretations, other reconsolidation-interfering drugs than translation inhibitors should be tested. Here we analyzed initially the UPS inhibitor effect in contextual conditioning in crabs. We found that UPS inhibition during consolidation impaired long-term memory. In contrast, UPS inhibition did not affect memory reconsolidation after contextual retrieval but, in fact, impeded memory labilization, blocking the action of drugs that does not affect directly the protein synthesis. To extend these finding to vertebrates, we performed similar experiments in contextual fear memory in mice. We found that the UPS inhibitor in hippocampus affected memory consolidation and blocked memory labilization after retrieval. These findings exclude alternative interpretations to the requirement of UPS in memory labilization and give evidence of this mechanism in both vertebrates and invertebrates.

Nuclear factor κB-dependent histone acetylation is specifically involved in persistent forms of memory.

Memory consolidation requires gene expression regulation by transcription factors, which eventually may induce chromatin modifications as histone acetylation. This mechanism is regulated by histone acetylases and deacetylases. It is not yet clear whether memory consolidation always recruits histone acetylation or it is only engaged in more persistent memories. To address this question, we used different strength of training for novel object recognition task in mice. Only strong training induced a long-lasting memory and an increase in hippocampal histone H3 acetylation. Histone acetylase inhibition in the hippocampus during consolidation impaired memory persistence, whereas histone deacetylase inhibition caused weak memory to persist. Nuclear factor κB (NF-κB) transcription factor inhibition impaired memory persistence and, concomitantly, reduced the general level of H3 acetylation. Accordingly, we found an important increase in H3 acetylation at a specific NF-κB-regulated promoter region of the Camk2d gene, which was reversed by NF-kB inhibition. These results show for the first time that histone acetylation is a specific molecular signature of enduring memories.

Calcineurin phosphatase as a negative regulator of fear memory in hippocampus: control on nuclear factor-κB signaling in consolidation and reconsolidation.

Protein phosphatases are important regulators of neural plasticity and memory. Some studies support that the Ca(2+) /calmodulin-dependent phosphatase calcineurin (CaN) is, on the one hand, a negative regulator of memory formation and, on the other hand, a positive regulator of memory extinction and reversal learning. However, the signaling mechanisms by which CaN exerts its action in such processes are not well understood. Previous findings support that CaN negatively regulate the nuclear factor kappaB (NF-κB) signaling pathway during extinction. Here, we have studied the role of CaN in contextual fear memory consolidation and reconsolidation in the hippocampus. We investigated the CaN control on the NF-κB signaling pathway, a key mechanism that regulates gene expression in memory processes. We found that post-training intrahippocampal administration of the CaN inhibitor FK506 enhanced memory retention one day but not two weeks after training. Accordingly, the inhibition of CaN by FK506 increased NF-κB activity in dorsal hippocampus. The administration of the NF-κB signaling pathway inhibitor sulfasalazine (SSZ) impeded the enhancing effect of FK506. In line with our findings in consolidation, FK506 administration before memory reactivation enhanced memory reconsolidation when tested one day after re-exposure to the training context. Strikingly, memory was also enhanced two weeks after training, suggesting that reinforcement during reconsolidation is more persistent than during consolidation. The coadministration of SSZ and FK506 blocked the enhancement effect in reconsolidation, suggesting that this facilitation is also dependent on the NF-κB signaling pathway. In summary, our results support a novel mechanism by which memory formation and reprocessing can be controlled by CaN regulation on NF-κB activity.

Pd-catalysed mono- and dicarbonylation of aryl iodides: insights into the mechanism and the selectivity.

The mechanism of the experimentally reported phosphine-free palladium-catalysed carbonylation of aryl iodides with amines in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as base was investigated at the DFT level. Paths were identified for both di- and monocarbonylation, and the calculated selectivity for three different substrates was in agreement with experiment. In dicarbonylation yielding α-ketoamides, formation of the second carbon-carbon bond occurs through reductive elimination in the Pd acyl amide intermediate after DBU-assisted nucleophilic attack of an amine at a terminal CO ligand. This path yields the major product with iodobenzene and the almost exclusive product with p-methoxyiodobenzene. Two different possible pathways yield the monocarbonylated amide product. In one of them, which affords the minor product for iodobenzene, base-assisted nucleophilic attack of the amine takes place on a Pd-bound acyl ligand. For substrates with electron-withdrawing substituents, such as p-cyanoiodobenzene, aryl migration to the CO ligand is disfavoured, and this allows base-assisted amine attack at a terminal CO ligand early in the catalytic cycle. From the resulting Pd amide aryl complex, the subsequent reductive elimination occurs easily, and monocarbonylation becomes favoured.

Viral Diseases in Water Buffalo (Bubalus bubalis): New Insights and Perspectives.

The water buffalo (Bubalus bubalis) has great adaptability to rustic environments and more variable conditions than cattle, who generally share the habitat. Diseases carried by buffaloes are relatively unknown and ignored and could be transmissible; an imbalance occurs between pathogens, environment, and susceptible hosts, generating a severe animal health problem. Also relevant is the effect of climate change on the populations of vectors that transmit viral diseases. The discovery of new virus variants that can pass from bovine (Bos) to buffalo or vice versa or to humans has highlighted the relevance of viruses crossing the host barrier. This review discusses the clinical viral diseases most reported in the water buffalo, characteristics, epidemiology, and recent findings about disease behavior, interaction with other species, the host, vectors, and pathogens. Diseases reviewed include Foot and Mouth Disease, Rinderpest, Malignant Catarrhal Fever, Infectious Bovine Rhinotracheitis, Bovine Viral Diarrhea, and Rabies. Also, vector-borne diseases include Lumpy Skin Disease, Ephemeral Fever, and Blue Tongue. The review also considers emerging viruses such as Buffalo Pox and Schmallenberg and, finally, other viruses such as papillomatosis. The knowledge and epidemiology of buffalo viral diseases must be constantly reconsidered and updated for adequate prevention and control programs.

Reconsolidation or extinction: transcription factor switch in the determination of memory course after retrieval.

In fear conditioning, aversive stimuli are readily associated with contextual features. A brief reexposure to the training context causes fear memory reconsolidation, whereas a prolonged reexposure induces memory extinction. The regulation of hippocampal gene expression plays a key role in contextual memory consolidation and reconsolidation. However, the mechanisms that determine whether memory will reconsolidate or extinguish are not known. Here, we demonstrate opposing roles for two evolutionarily related transcription factors in the mouse hippocampus. We found that nuclear factor-κB (NF-κB) is required for fear memory reconsolidation. Conversely, calcineurin phosphatase inhibited NF-κB and induced nuclear factor of activated T-cells (NFAT) nuclear translocation in the transition between reconsolidation and extinction. Accordingly, the hippocampal inhibition of both calcineurin and NFAT independently impaired memory extinction, whereas inhibition of NF-κB enhanced memory extinction. These findings represent the first insight into the molecular mechanisms that determine memory reprocessing after retrieval, supporting a transcriptional switch that directs memory toward reconsolidation or extinction. The precise molecular characterization of postretrieval processes has potential importance to the development of therapeutic strategies for fear memory disorders.

Physiological and Behavioral Mechanisms of Thermoregulation in Mammals.

This review analyzes the main anatomical structures and neural pathways that allow the generation of autonomous and behavioral mechanisms that regulate body heat in mammals. The study of the hypothalamic neuromodulation of thermoregulation offers broad areas of opportunity with practical applications that are currently being strengthened by the availability of efficacious tools like infrared thermography (IRT). These areas could include the following: understanding the effect of climate change on behavior and productivity; analyzing the effects of exercise on animals involved in sporting activities; identifying the microvascular changes that occur in response to fear, pleasure, pain, and other situations that induce stress in animals; and examining thermoregulating behaviors. This research could contribute substantially to understanding the drastic modification of environments that have severe consequences for animals, such as loss of appetite, low productivity, neonatal hypothermia, and thermal shock, among others. Current knowledge of these physiological processes and complex anatomical structures, like the nervous systems and their close relation to mechanisms of thermoregulation, is still limited. The results of studies in fields like evolutionary neuroscience of thermoregulation show that we cannot yet objectively explain even processes that on the surface seem simple, including behavioral changes and the pathways and connections that trigger mechanisms like vasodilatation and panting. In addition, there is a need to clarify the connection between emotions and thermoregulation that increases the chances of survival of some organisms. An increasingly precise understanding of thermoregulation will allow us to design and apply practical methods in fields like animal science and clinical medicine without compromising levels of animal welfare. The results obtained should not only increase the chances of survival but also improve quality of life and animal production.

Pathophysiology of Fever and Application of Infrared Thermography (IRT) in the Detection of Sick Domestic Animals: Recent Advances.

Body-temperature elevations are multifactorial in origin and classified as hyperthermia as a rise in temperature due to alterations in the thermoregulation mechanism; the body loses the ability to control or regulate body temperature. In contrast, fever is a controlled state, since the body adjusts its stable temperature range to increase body temperature without losing the thermoregulation capacity. Fever refers to an acute phase response that confers a survival benefit on the body, raising core body temperature during infection or systemic inflammation processes to reduce the survival and proliferation of infectious pathogens by altering temperature, restriction of essential nutrients, and the activation of an immune reaction. However, once the infection resolves, the febrile response must be tightly regulated to avoid excessive tissue damage. During fever, neurological, endocrine, immunological, and metabolic changes occur that cause an increase in the stable temperature range, which allows the core body temperature to be considerably increased to stop the invasion of the offending agent and restrict the damage to the organism. There are different metabolic mechanisms of thermoregulation in the febrile response at the central and peripheral levels and cellular events. In response to cold or heat, the brain triggers thermoregulatory responses to coping with changes in body temperature, including autonomic effectors, such as thermogenesis, vasodilation, sweating, and behavioral mechanisms, that trigger flexible, goal-oriented actions, such as seeking heat or cold, nest building, and postural extension. Infrared thermography (IRT) has proven to be a reliable method for the early detection of pathologies affecting animal health and welfare that represent economic losses for farmers. However, the standardization of protocols for IRT use is still needed. Together with the complete understanding of the physiological and behavioral responses involved in the febrile process, it is possible to have timely solutions to serious problem situations. For this reason, the present review aims to analyze the new findings in pathophysiological mechanisms of the febrile process, the heat-loss mechanisms in an animal with fever, thermoregulation, the adverse effects of fever, and recent scientific findings related to different pathologies in farm animals through the use of IRT.

Phosphine ligands in the palladium-catalysed methoxycarbonylation of ethene: insights into the catalytic cycle through an HP NMR spectroscopic study.

Novel cis-1,2-bis(di-tert-butyl-phosphinomethyl) carbocyclic ligands 6-9 have been prepared and the corresponding palladium complexes [Pd(O(3)SCH(3))(L-L)][O(3)SCH(3)] (L-L=diphosphine) 32-35 synthesised and characterised by NMR spectroscopy and X-ray diffraction. These diphosphine ligands give very active catalysts for the palladium-catalysed methoxycarbonylation of ethene. The activity varies with the size of the carbocyclic backbone, ligands 7 and 9, containing four- and six-membered ring backbones giving more active systems. The acid used as co-catalyst has a strong influence on the activity, with excess trifluoroacetic acid affording the highest conversion, whereas excess methyl sulfonic acid inhibits the catalytic system. An in operando NMR spectroscopic mechanistic study has established the catalytic cycle and resting state of the catalyst under operating reaction conditions. Although the catalysis follows the hydride pathway, the resting state is shown to be the hydride precursor complex [Pd(O(3)SCH(3))(L-L)][O(3)SCH(3)], which demonstrates that an isolable/detectable hydride complex is not a prerequisite for this mechanism.

Sustained CaMKII Delta Gene Expression Is Specifically Required for Long-Lasting Memories in Mice.

Although important information is available on the molecular mechanisms of long-term memory formation, little is known about the processes underlying memory persistence in the brain. Here, we report that persistent gene expression of CaMKIIδ isoform participates in object recognition long-lasting memory storage in mice hippocampus. We found that CaMKIIδ mRNA expression was sustained up to one week after training and paralleled memory retention. Antisense DNA infusion in the hippocampus during consolidation or even after consolidation impairs 7-day- but not 1-day-long memory, supporting a role of CaMKIIδ in memory persistence. CaMKIIδ gene expression was accompanied by long-lasting nucleosome occupancy changes at its promoter. This epigenetic mechanism is described for the first time in a memory process and offers a novel mechanism for persistent gene expression in neurons. CaMKIIδ protein is mainly present in nucleus and presynaptic terminals, suggesting a role in these subcellular compartments for memory persistence. All these results point to a key function of the sustained gene expression of this overlooked CaMKII isoform in long-lasting memories.

The lateral neocortex is critical for contextual fear memory reconsolidation.

Memories are a product of the concerted activity of many brain areas. Deregulation of consolidation and reprocessing of mnemonic traces that encode fearful experiences might result in fear-related psychopathologies. Here, we assessed how pre-established memories change with experience, particularly the labilization/reconsolidation of memory, using the whole-brain analysis technique of positron emission tomography in male mice. We found differences in glucose consumption in the lateral neocortex, hippocampus and amygdala in mice that underwent labilization/reconsolidation processes compared to animals that did not reactivate a fear memory. We used chemogenetics to obtain insight into the role of cortical areas in these phases of memory and found that the lateral neocortex is necessary for fear memory reconsolidation. Inhibition of lateral neocortex during reconsolidation altered glucose consumption levels in the amygdala. Using an optogenetic/neuronal recording-based strategy we observed that the lateral neocortex is functionally connected with the amygdala, which, along with retrograde labeling using fluorophore-conjugated cholera toxin subunit B, support a monosynaptic connection between these areas and poses this connection as a hot-spot in the circuits involved in reactivation of fear memories.

Activation of hippocampal nuclear factor-kappa B by retrieval is required for memory reconsolidation.

Initially, memory is labile and requires consolidation to become stable. However, several studies support that consolidated memories can undergo a new period of lability after retrieval. The mechanistic differences of this process, termed reconsolidation, with the consolidation process are under debate, including the participation of hippocampus. Up to this point, few reports describe molecular changes and, in particular, transcription factor (TF) involvement in memory restabilization. Increasing evidence supports the participation of the TF nuclear factor-kappaB (NF-kappaB) in memory consolidation. Here, we demonstrate that the inhibition of NF-kappaB after memory reactivation impairs retention of a hippocampal-dependent inhibitory avoidance task in mice. We used two independent disruptive strategies to reach this conclusion. First, we administered intracerebroventricular or intrahippocampal sulfasalazine, an inhibitor of IKK (IkappaB kinase), the kinase that activates NF-kappaB. Second, we infused intracerebroventricular or intrahippocampal kappaB decoy, a direct inhibitor of NF-kappaB consisting of a double-stranded DNA oligonucleotide that contains the kappaB consensus sequence. When injected immediately after memory retrieval, sulfasalazine or kappaB decoy (Decoy) impaired long-term retention. In contrast, a one base mutated kappaB decoy (mDecoy) had no effect. Furthermore, we also found NF-kappaB activation in the hippocampus, with a peak 15 min after memory retrieval. This activation was earlier than that found during consolidation. Together, these results indicate that NF-kappaB is an important transcriptional regulator in memory consolidation and reconsolidation in hippocampus, although the temporal kinetics of activation differs between the two processes.

Effects of Hippocampal LIMK Inhibition on Memory Acquisition, Consolidation, Retrieval, Reconsolidation, and Extinction.

Long-lasting changes in dendritic spines provide a physical correlate for memory formation and persistence. LIM kinase (LIMK) plays a critical role in orchestrating dendritic actin dynamics during memory processing, since it is the convergent downstream target of both the Rac1/PAK and RhoA/ROCK pathways that in turn induce cofilin phosphorylation and prevent depolymerization of actin filaments. Here, using a potent LIMK inhibitor (BMS-5), we investigated the role of LIMK activity in the dorsal hippocampus during contextual fear memory in rats. We first found that post-training administration of BMS-5 impaired memory consolidation in a dose-dependent manner. Inhibiting LIMK before training also disrupted memory acquisition. We then demonstrated that hippocampal LIMK activity seems to be critical for memory retrieval and reconsolidation, since both processes were impaired by BMS-5 treatment. Contextual fear memory extinction, however, was not sensitive to the same treatment. In conclusion, our findings demonstrate that hippocampal LIMK activity plays an important role in memory acquisition, consolidation, retrieval, and reconsolidation during contextual fear conditioning.

NF-κB transcription factor role in consolidation and reconsolidation of persistent memories.

Transcriptional regulation is an important molecular process required for long-term neural plasticity and long-term memory (LTM) formation. Thus, one main interest in molecular neuroscience in the last decades has been the identification of transcription factors that are involved in memory processes. Among them, the nuclear factor κB (NF-κB) family of transcription factors has gained interest due to a significant body of evidence that supports a key role of these proteins in synaptic plasticity and memory. In recent years, the interest was particularly reinforced because NF-κB was characterized as an important regulator of synaptogenesis. This function may be explained by its participation in synapse to nucleus communication, as well as a possible local role at the synapse. This review provides an overview of experimental work obtained in the last years, showing the essential role of this transcription factor in memory processes in different learning tasks in mammals. We focus the review on the consolidation and reconsolidation memory phases as well as on the regulation of immediate-early and late genes by epigenetic mechanisms that determine enduring forms of memories.

Epigenetic mechanisms and memory strength: a comparative study.

Memory consolidation requires de novo mRNA and protein synthesis. Transcriptional activation is controlled by transcription factors, their cofactors and repressors. Cofactors and repressors regulate gene expression by interacting with basal transcription machinery, remodeling chromatin structure and/or chemically modifying histones. Acetylation is the most studied epigenetic mechanism of histones modifications related to gene expression. This process is regulated by histone acetylases (HATs) and histone deacetylases (HDACs). More than 5 years ago, we began a line of research about the role of histone acetylation during memory consolidation. Here we review our work, presenting evidence about the critical role of this epigenetic mechanism during consolidation of context-signal memory in the crab Neohelice granulata, as well as during consolidation of novel object recognition memory in the mouse Mus musculus. Our evidence demonstrates that histone acetylation is a key mechanism in memory consolidation, functioning as a distinctive molecular feature of strong memories. Furthermore, we found that the strength of a memory can be characterized by its persistence or its resistance to extinction. Besides, we found that the role of this epigenetic mechanism regulating gene expression only in the formation of strongest memories is evolutionarily conserved.