Navegando por Autor "Radiske, Andressa"

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Avoidance memory requires CaMKII activity to persist after recall
(2021-11-14) Radiske, Andressa; Gonzalez, Maria Carolina; Rossato, Janine Inez; Apolinário, Gênedy Karielly da Silva; Oliveira, João R. de; Bevilaqua, Lia Rejane Müller; Cammarota, Martín Pablo
Avoidance memory is destabilized when recalled concurrently with conficting information, and must undergo a hippocampus-dependent restabilization process called reconsolidation to persist. CaMKII is a serine/threonine protein kinase essential for memory processing; however, its possible involvement in avoidance memory reconsolidation has not yet been studied. Using pharmacological, electrophysiological and optogenetic tools, we found that in adult male Wistar rats hippocampal CaMKII is necessary to reconsolidate avoidance memory, but not to keep it stored while inactive, and that blocking reconsolidation via CaMKII inhibition erases learned avoidance responses
BDNF controls object recognition memory reconsolidation
(2017) Radiske, Andressa; Rossato, Janine I.; Gonzalez, Maria Carolina; Köhler, Cristiano A.; Bevilaqua, Lia Rejane Müller; Cammarota, Martín Pablo
Reconsolidation restabilizes memory after reactivation. Previously, we reported that the hippocampus is engaged in object recognition memory reconsolidation to allow incorporation of new information into the original engram. Here we show that BDNF is sufficient for this process, and that blockade of BDNF function in dorsal CA1 impairs updating of the reactivated recognition memory trace.
Consolidation of Object Recognition Memory Requires HRI Kinase-Dependent Phosphorylation of eIF2a in the Hippocampus
(2013) ILL-Raga, Gerard; Kohler, Cristiano; Radiske, Andressa; Lima, Ramón H.; Rosen, Mark D.; Muñoz, Francisco J.; Cammarota, Martín Pablo
Local control of protein synthesis at synapses is crucial for synaptic plasticity and memory formation. However, little is known about the signals coupling neurotransmitter release with the translational machinery during these processes. Here, we studied the involvement of heme-regulated inhibitor (HRI) kinase, a kinase activated by nitric oxide that phosphorylates eukaryotic initiation factor 2α (eIF2α), in object recognition (OR) memory consolidation. Phosphorylated eIF2α mediates two opposing effects upon translation: translational arrest of most mRNAs and translational activation of selected mRNAs bearing specific features in their 5'untranslated regions (5'UTRs). We found that HRI kinase activation in the CA1 region of the dorsal hippocampus is necessary for retention of OR memory in rats. Accordingly, learning induced a transient increase in the phosphorylation state of eIF2α in dorsal CA1 which was abolished by the HRI kinase inhibitor N-(2,6-dimethylbenzyl)-6,7-dimethoxy-2H-[1]benzofuro[3,2-c]pyrazol-3-amine hydrochloride (AMI). The increase in p-eIF2α was associated with increased expression of BACE1 and activating transcription factor 4, two proteins containing eIF2α-responsive 5'UTRs in their mRNAs that play a key role in synaptic plasticity. Our data suggests that learning promotes the transient phosphorylation of eIF2α to allow for translation of specific 5'UTR-mRNAs through a process requiring HRI kinase activation.
Consolidation of object recognition memory requires simultaneous activation of dopamine D1/D5 receptors in the amygdala and medial prefrontal cortex but not in the hippocampus
(2013-11) Rossato, Janine I.; Radiske, Andressa; Kohler, Cristiano A.; Gonzalez, Carolina; Bevilaqua, Lia Rejane Müller; Medina, Jorge H.; Cammarota, Martín Pablo
The mesocorticolimbic dopaminergic system includes the ventral tegmental area (VTA) and its projections to the amygdala (AMY), the hippocampus (HIP) and the medial prefrontal cortex (mPFC), among others. Object recognition (OR) long-term memory (LTM) processing requires dopaminergic activity but, although some of the brain regions mentioned above are necessary for OR LTM consolidation, their possible dopamine-mediated interplay remains to be analyzed. Using adult male Wistar rats, we found that posttraining microinjection of the dopamine D1/D5 receptor antagonist SCH23390 in mPFC or AMY, but not in HIP, impaired OR LTM. The dopamine D2 receptor agonist quinpirole had no effect on retention. VTA inactivation also hindered OR LTM, and even though this effect was unaffected by co-infusion of the dopamine D1/D5 receptor agonist SKF38393 in HIP, mPFC or AMY alone, it was reversed by simultaneous activation of D1/D5 receptors in the last two regions. Our results demonstrate that the mesocorticolimbic dopaminergic system is indeed essential for OR LTM consolidation and suggest that the role played by some of its components during this process is much more complex than previously thought.
Cross-frequency phase-amplitude coupling between hippocampal theta and gamma oscillations during recall destabilizes memory and renders it susceptible to reconsolidation disruption
(Society for Neuroscience, 2020-07-13) Radiske, Andressa; Gonzalez, Maria Carolina; Ocazionez, Sergio Andrés Conde; Rossato, Janine Inez; Köhler, Cristiano André; Cammarota, Martín Pablo
Avoidance memory reactivation at recall triggers hippocampal theta-gamma phase amplitude coupling (hPAC) only when it elicits hippocampus-dependent reconsolidation. However, it is not known whether there is a causal relationship between these phenomena. We found that in adult male Wistar rats, silencing the medial septum during recall did not affect avoidance memory expression or maintenance but abolished hPAC and the amnesia caused by the intra-hippocampal administration of reconsolidation blockers, both of which were restored by concomitant theta burst stimulation of the fimbria-fornix pathway. Remarkably, artificial hPAC generated by fimbria-fornix stimulation during recall of a learned avoidance response naturally resistant to hippocampus-dependent reconsolidation made it susceptible to reactivation-dependent amnesia. Our results indicate that hPAC mediates the destabilization required for avoidance memory reconsolidation, and suggest that generation of artificial hPAC at recall overcomes the boundary conditions of this process.
Dopamine controls whether new declarative information updates reactivated memories through reconsolidation
(2021-07-12) Gonzalez, Maria Carolina; Rossato, Janine Inez; Radiske, Andressa; Bevilaqua, Lia Rejane Muller; Cammarota, Martín Pablo
Consolidation and reconsolidation are independent memory processes. Consolidation stabilizes new memories, whereas reconsolidation restabilizes memories destabilized when reactivated during recall. However, the biological role of the destabilization/reconsolidation cycle is still unknown. It has been hypothesized that reconsolidation links new information with reactivated memories, but some reports suggest that new and old memories are associated through consolidation mechanisms instead. Object-recognition memory (ORM) serves to judge the familiarity of items and is essential for remembering previous events. We took advantage of the fact that ORM consolidation, destabilization, and reconsolidation can be pharmacologically dissociated to demonstrate that, depending on the activation state of hippocampal dopamine D1/D5 receptors, the memory of a novel object presented during recall of the memory of a familiar one can be formed via reconsolidation or consolidation, but only reconsolidation can link them. We also found that recognition memories formed through reconsolidation can be destabilized even if indirectly reactivated. Our results indicate that dopamine couples novelty detection with memory destabilization to determine whether a new recognition trace is associated with an active network and suggest that declarative reminders should be used with caution during reconsolidation-based psychotherapeutic interventions
Editorial: On the destabilization of maladaptive memory: updates and future perspectives
(Frontiers Media SA, 2024-01) Radiske, Andressa; Cahill, Emma N.; Milton, Amy L.; Cammarota, Martín Pablo
Intense fear induces persistent memories that can result in exacerbated maladaptive avoidance and lead to the development of phobias and other anxiety disorders. Similarly, drug addiction has been related to the formation of strong pervasive memories that trigger craving and relapse. Long-lasting consolidated memories can become destabilized when reactivated and, to endure, must undergo a protein synthesis-dependent restabilization in a process called reconsolidation (Nader et al., 2000). Because inhibition of memory restabilization appears to cause amnesia in laboratory animals, it has been suggested that therapies based on the pharmacological or behavioral modulation of this process may be useful to treat anxiety or addiction-related disorders (Monfils and Holmes, 2018). Although our knowledge about the molecular basis of memory reconsolidation has grown exponentially during the last two decades, there is no widespread reconsolidation therapy yet, and large-scale clinical trials are yet to be conducted. Furthermore, it is usually impractical and sometimes unethical, to reenact the behavioral and emotional conditions required for successful memory destabilization during psychotherapy, and the boundary conditions for ‘real life' memories (as opposed to those generated by experimental procedures) are not fully understood. To overcome this limitation, it has been argued that basic research should focus on elucidating the molecular and physiological signatures of reactivation-induced memory destabilization to determine specific reconsolidation biomarkers (Radiske et al., 2020; Milton et al., 2023). In this Research Topic, we have compiled original research articles presenting the latest findings on the mechanisms underlying memory destabilization
GluN2B and GluN2A containing NMDAR are differentially involved in extinction memory destabilization and restabilization during reconsolidation
(Springer Science and Business Media LLC, 2021-01-08) Radiske, Andressa; Gonzalez, Maria Carolina; Ferreira, Diana Aline Nôga Morais; Rossato, Janine Inez; Bevilaqua, Lia Rejane Müller; Cammarota, Martín Pablo
Extinction memory destabilized by recall is restabilized through mTOR-dependent reconsolidation in the hippocampus, but the upstream pathways controlling these processes remain unknown. Hippocampal NMDARs drive local protein synthesis via mTOR signaling and may control active memory maintenance. We found that in adult male Wistar rats, intra dorsal-CA1 administration of the non-subunit selective NMDAR antagonist AP5 or of the GluN2A subunit-containing NMDAR antagonist TCN201 after step down inhibitory avoidance (SDIA) extinction memory recall impaired extinction memory retention and caused SDIA memory recovery. On the contrary, pre-recall administration of AP5 or of the GluN2B subunit-containing NMDAR antagonist RO25-6981 had no effect on extinction memory recall or retention per se but hindered the recovery of the avoidance response induced by post-recall intra-CA1 infusion of the mTOR inhibitor rapamycin. Our results indicate that GluN2B-containing NMDARs are necessary for extinction memory destabilization whereas GluN2A-containing NMDARs are involved in its restabilization, and suggest that pharmacological modulation of the relative activation state of these receptor subtypes around the moment of extinction memory recall may regulate the dominance of extinction memory over the original memory trace
Hippocampal CaMKII inhibition induces reactivation-dependent amnesia for extinction memory and causes fear relapse
(Springer Science and Business Media LLC, 2023-12) Radiske, Andressa; Castro, Carla Miranda de; Rossato, Janine Inez; Gonzalez, Maria Carolina; Cammarota, Martín Pablo
Hippocampal GluN2B subunit-containing NMDAR (GluN2B-NMDAR) activation during recall destabilizes fear extinction memory, which must undergo brain-derived neurotrophic factor (BDNF)-dependent reconsolidation to persist. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a Ser/Thr protein kinase essential for hippocampus-dependent memory processing that acts downstream GluN2B-NMDAR and controls BDNF expression, but its participation in fear extinction memory reconsolidation has not yet been studied. Using a combination of pharmacological and behavioral tools, we found that in adult male Wistar rats, intra dorsal-CA1 administration of the CaMKII inhibitors autocamtide-2-related inhibitory peptide (AIP) and KN-93, but not of their inactive analogs scrambled AIP and KN-92, after fear extinction memory recall impaired extinction and caused GluN2B-NMDAR-dependent recovery of fear. Our results indicate that hippocampal CaMKII is necessary for fear extinction reconsolidation, and suggest that modulation of its activity around the time of recall controls the inhibition that extinction exerts on learned fear
Implementação da técnica de registro extracelular multicanal no cérebro de roedores in vivo
(Universidade Federal do Rio Grande do Norte, 2023-12-13) Araújo, Raquel Lúcia Souto de; Cammarota, Martín Pablo; Arrais Júnior, Ernano; http://lattes.cnpq.br/4024477389642547; 0000-0001-9741-5074; http://lattes.cnpq.br/4888317387600937; http://lattes.cnpq.br/0623474419062785; Radiske, Andressa; 0000-0002-8945-3182; http://lattes.cnpq.br/0783119632703107; Rossato, Janine Inez; 0000-0002-7980-5842; http://lattes.cnpq.br/8136970112250481
As técnicas de aquisição do sinal cerebral podem ser não invasivas ou invasivas. Nas técnicas não invasivas a mais utilizada é a de superfície, conhecida como EEG, enquanto nas técnicas invasivas, o ECOG é a mais difundida. Em ratos, a matriz de microeletrodos multicanal é um dispositivo de registro eletrofisiológico extracelular que permitiu avanços na área ao viabilizar o monitoramento prolongado e simultâneo de diversas células. Portanto, se faz necessário a elaboração documentada de protocolos eficientes de manufatura desses dispositivos. O objetivo deste trabalho é a implementação da técnica de registro extracelular multicanal no cérebro de roedores in vivo. Para isso, foram confeccionadas e implantadas duas matrizes de 16 microeletrodos na região CA1 do hipocampo de ratos Wistar adultos. Os resultados demonstram que o dispositivo confeccionado e implantado é capaz de realizar o registro eletrofisiológico. Com a implementação da técnica, é possível investigar distintas camadas de grupos neuronais em uma determinada região.
Inactivation of the dorsal hippocampus or the medial prefrontal cortex impairs retrieval but has differential effect on spatial memory reconsolidation
(2015) Rossato, Janine I.; Köhler, Cristiano A.; Radiske, Andressa; Bevilaqua, Lia Rejane Müller; Cammarota, Martín Pablo
Active memories can incorporate new information through reconsolidation. However, the notion that memory retrieval is necessary for reconsolidation has been recently challenged. Non-reinforced retrieval induces hippocampus and medial prefrontal cortex (mPFC)-dependent reconsolidation of spatial memory in the Morris water maze (MWM). We found that the effect of protein synthesis inhibition on this process is abolished when retrieval of the learned spatial preference is hindered through mPFC inactivation but not when it is blocked by deactivation of dorsal CA1. Our results do not fully agree with the hypothesis that retrieval is unneeded for reconsolidation. Instead, they support the idea that a hierarchic interaction between the hippocampus and the mPFC controls spatial memory in the MWM, and indicate that this cortex is sufficient to retrieve the information essential to reconsolidate the spatial memory trace, even when the hippocampus is inactivated.
mTOR inhibition impairs extinction memory reconsolidation
(Cold Spring Harbor Laboratory, 2020-12-15) Radiske, Andressa; Gonzalez, Maria Carolina; Ferreira, Diana Aline Nôga Morais; Rossato, Janine Inez; Bevilaqua, Lia Rejane Müller; Cammarota, Martín Pablo
Fear-motivated avoidance extinction memory is prone to hippocampal brain-derived neurotrophic factor (BDNF)-dependent reconsolidation upon recall. Here, we show that extinction memory recall activates mammalian target of rapamycin (mTOR) in dorsal CA1, and that post-recall inhibition of this kinase hinders avoidance extinction memory persistence and recovers the learned aversive response. Importantly, coadministration of recombinant BDNF impedes the behavioral effect of hippocampal mTOR inhibition. Our results demonstrate that mTOR signaling is necessary for fear-motivated avoidance extinction memory reconsolidation and suggests that BDNF acts downstream mTOR in a protein synthesis-independent manner to maintain the reactivated extinction memory trace
Nicotine modulates the long-lasting storage of fear memory
(2013) Lima, Ramón H.; Radiske, Andressa; Köhler, Cristiano A.; Gonzalez, Maria Carolina; Bevilaqua, Lia Rejane Müller; Rossato, Janine I.; Medina, Jorge H.; Cammarota, Martín Pablo
Late post-training activation of the ventral tegmental area (VTA)–hippocampus dopaminergic loop controls the entry of information into long-term memory (LTM). Nicotinic acetylcholine receptors (nAChR) modulate VTA function, but their involvement in LTM storage is unknown. Using pharmacological and behavioral tools, we found that α7-nAChR-mediated cholinergic interactions between the pedunculopontine tegmental nucleus and the medial prefrontal cortex modulate the duration of fear-motivated memories, maybe by regulating the activation state of VTA–hippocampus dopamine connections.
NMDARs control object recognition memory destabilization and reconsolidation
(Elsevier BV, 2023-04) Rossato, Janine Inez; Radiske, Andressa; Gonzalez, Maria Carolina; Apolinário, Gênedy Karielly da Silva; Araújo, Raquel Lúcia Souto de; Bevilaqua, Lia Rejane Muller; Cammarota, Martín Pablo
Object recognition memory (ORM) allows identification of previously encountered items and is therefore crucial for remembering episodic information. In rodents, reactivation during recall in the presence of a novel object destabilizes ORM and initiates a Zif268 and protein synthesis-dependent reconsolidation process in the hippocampus that links the memory of this object to the reactivated recognition trace. Hippocampal NMDA receptors (NMDARs) modulate Zif268 expression and protein synthesis and regulate memory stability but their possible involvement in the ORM destabilization/reconsolidation cycle has yet to be analyzed in detail. We found that, in adult male Wistar rats, intra dorsal-CA1 administration of the non-subunit selective NMDAR antagonist AP5, or of the GluN2A subunit-containing NMDAR antagonist TCN201, 5 min after an ORM reactivation session in the presence of a novel object carried out 24 h post-training impaired retention 24 h later. In contrast, pre-reactivation administration of the GluN2B subunit-containing NMDAR antagonist RO25-6981 had no effect on ORM recall or retention but impeded the amnesia caused by Zif268 silencing and protein synthesis inhibition in dorsal CA1. Our results indicate that GluN2B-containing hippocampal NMDARs are necessary for ORM destabilization whereas GluN2A-containing NMDARs are involved in ORM reconsolidation, and suggest that modulation of the relative activity of these receptor subtypes during recall regulates ORM persistence
O papel da proteína PKMζ na reconsolidação da memória espacial
(Universidade Federal do Rio Grande do Norte, 2025-03-28) Oliveira, João Rodrigo de; Cammarota, Martin Pablo; Rossato, Janine Inez; https://orcid.org/0000-0001-9741-5074; http://lattes.cnpq.br/4888317387600937; http://lattes.cnpq.br/5484542566865202; Gavioli, Elaine Cristina; Rachetti, Vanessa de Paula Soares; Radiske, Andressa; Lima, Ramón Hypolito
Um requisito fundamental da vida cotidiana é codificar e evocar com sucesso a localização de objetos, pontos de referência ou locais no espaço. A perda desta capacidade é um dos primeiros sintomas de comprometimento cognitivo na Doença de Alzheimer, sendo frequentemente investigada em roedores utilizando o labirinto aquático de Morris (LAM). Durante o treino no LAM os animais utilizam pistas espaciais para formar uma representação espacial do entorno e as utilizam para encontrar uma plataforma submersa que serve como escape. Contudo, se a plataforma não é encontrada, os animais devem reavaliar sua memória e, provavelmente, modificá-la através de um processo de reconsolidação. Foi sugerido que o hipocampo participa da reconsolidação de vários tipos de memória através de mecanismos que envolvem a sinalização mediada pela PKMζ, uma isoforma atípica da PKC, que tem sido implicada na manutenção da memória de longa duração. No entanto, o papel desta proteína na reconsolidação da memória espacial ainda não é entendido. Este trabalho investigou a participação da PKMζ na reconsolidação da memória espacial em ratos Wistar. Observamos que a infusão intra-hipocampal de ZIP, peptídeo inibidor da PKMζ, ou do oligonucleotídeo antisense para PKMζ, imediatamente após um teste na ausência de plataforma de escape, impede a persistência da memória espacial. O efeito amnésico promovido pelo ZIP é bloqueado pela administração pré-teste do antagonista dos receptores NMDA-GluN2B, e pela inibição do proteassomo. Também encontramos que a amnésia promovida por ZIP é mimetizada pela inibição da inserção de receptores AMPA na sinapse, e revertida pela co-infusão de um bloqueador da internalização destes receptores. Essas descobertas indicam que a PKMζ hipocampal é essencial para a persistência de uma preferência espacial após sua reativação não reforçada, em de uma estreita janela de tempo, e que esse efeito pode ser mediado via modulação da atividade dos receptores AMPA.
On the effect of hippocampal c-Jun N-terminal kinase inhibition on object recognition memory
(Frontiers Media SA, 2022-12) Rossato, Janine Inez; Radiske, Andressa; Gonzalez, Maria Carolina; Bevilaqua, Lia Rejane Muller; Cammarota, Martín Pablo
c-Jun N-terminal kinase (JNK) phosphorylates the transcription factor c-Jun in response to stress stimuli and contributes to both hippocampal synaptic plasticity and memory processing in mammals. Object recognition memory (ORM) is essential for remembering facts and events. In rodents, ORM consolidation and reconsolidation require a functional hippocampus. However, the possible involvement of hippocampal JNK on ORM processing has not yet been studied. Here we show that when injected into dorsal CA1 5 min, but not 6 h, after training adult male rats in the novel object recognition learning task, the JNK inhibitor SP600125 impaired ORM for at least 7 days without affecting exploratory activity, short-term ORM retention, or the functional integrity of the hippocampus. SP600125 did not hinder ORM retention when given in CA1 after a memory reactivation session carried out 24 h post-training in the presence of the same two objects presented during the training session, but caused time-dependent amnesia when one of the objects presented at training was replaced by a different but behaviorally equivalent novel one. Taken together, our results indicate that hippocampal JNK activity is necessary for ORM consolidation and reconsolidation but not for ORM recall or short-term retention
On the involvement of BDNF signaling in memory reconsolidation
(2019-08) Gonzalez, Maria Carolina; Radiske, Andressa; Cammarota, Martín Pablo
When retrieval occurs concomitantly with novelty detection, mismatch perception or reactivation of conflicting information, consolidated memories can enter into a labile state, and to persist, must be restabilized through a protein synthesis-dependent reconsolidation process during which their strength and content can be modified. Extensive literature implicates brain-derived neurotrophic factor (BDNF), a key regulator of synaptogenesis and synaptic plasticity, in the acquisition, consolidation and extinction of several memory types. However, the participation of BDNF in memory reconsolidation has been less studied. In this review, we discuss recent reports supporting the involvement of BDNF signaling in reactivation-induced memory updating.
Optogenetic inactivation of the medial septum impairs long-term object recognition memory formation
(Springer Science and Business Media LLC, 2022-06-07) Gonzalez, Maria Carolina; Radiske, Andressa; Rossato, Janine; Conde-Ocazionez, Sergio; Bevilaqua, Lia Rejane Muller; Cammarota, Martin Pablo
Theta is one of the most prominent extracellular synchronous oscillations in the mammalian brain. Hippocampal theta relies on an intact medial septum (MS) and has been consistently recorded during the training phase of some learning paradigms, suggesting that it may be implicated in hippocampus-dependent long-term memory processing. Object recognition memory (ORM) allows animals to identify familiar items and is essential for remembering facts and events. In rodents, long-term ORM formation requires a functional hippocampus but the involvement of the MS in this process remains controversial. We found that training adult male Wistar rats in a long-term ORM-inducing learning task involving exposure to two different, but behaviorally equivalent novel stimuli objects increased hippocampal theta power, and that suppressing theta via optogenetic MS inactivation caused amnesia. Importantly, the amnesia was specific to the object the animals were exploring when the MS was inactivated. Taken together, our results indicate that the MS is necessary for long-term ORM formation and suggest that hippocampal theta activity is causally linked to this process
Papel do sistema Nociceptina/Orfanina FQ – receptor NOP no processamento da memória de reconhecimento de objetos
(Universidade Federal do Rio Grande do Norte, 2024-12-14) Santos, Elis Brisa dos; Rossato, Janine Inez; https://orcid.org/0000-0002-7980-5842; http://lattes.cnpq.br/8136970112250481; https://orcid.org/0000-0001-7367-9243; http://lattes.cnpq.br/0419800615782483; Radiske, Andressa; https://orcid.org/0000-0002-8945-3182; http://lattes.cnpq.br/0783119632703107; Gavioli, Elaine Cristina; https://orcid.org/0000-0001-8967-1369; http://lattes.cnpq.br/1759328747578795
A nociceptina/orfanina FQ (N/OFQ) é um peptídeo endógeno de 17 aminoácidos relacionado aos peptídeos opióides, mas que possui seu próprio receptor, NOP. Em sua via canônica, a atividade do receptor NOP medeia abertura e fechamento de canais iônicos que induzem a inibição da atividade neural e, por estar amplamente distribuídos no SNC, sendo particularmente abundantes em áreas corticais e límbicas (hipocampo, giro denteado, áreas septais e amígdala), sugere-se que esse receptor esteja diretamente associado ao processamento cognitivo complexo. De fato, o sistema N/OFQ - NOP é capaz de modular o processamento nociceptivo, de aprendizado, do estado emocional, do controle neuroendócrino, da ingestão de alimentos, do controle motor e das vias de recompensa e prazer. Trabalhos anteriores demonstraram que o receptor NOP participa da formação de diversas memórias, como as aversivas e espaciais, porém pouco se sabe de sua participação nas memórias de reconhecimento. O objetivo central deste trabalho é avaliar o papel do sistema N/OFQ - NOP hipocampal nas diferentes fases do processamento da memória de reconhecimento de objetos, utilizando ratos como modelos experimentais. Como principais achados, verificamos que a ativação dos receptores NOP hipocampais antes da sessão de treino, prejudica a formação da memória de reconhecimento, porém quando administrada imediatamente após o treino esse efeito amnésico não é observado, mostrando que esse receptor tem papel na formação do engrama mnemônico, porém não na sua estabilização a longo prazo. Para garantir que esse efeito não ocorreu em detrimento de fatores inespecíficos, verificamos que as diferentes doses utilizadas nesse estudo não foram capazes de modificar o comportamento exploratório e ambulatório dos animais, tampouco modificou estados relacionados à ansiedade nos animais experimentais. Esses achados representam avanços no entendimento da ação do receptor NOP na região do hipocampo e abre caminho para que novos estudos envolvendo sua ação em outros processos cognitivos sejam realizados.
PKMζ inhibition disrupts reconsolidation and erases object recognition memory
(2019-03-06) Rossato, Janine I.; Gonzalez, Maria Carolina; Radiske, Andressa; Apolinário, Gênedy; Conde-Ocazionez, Sergio; Bevilaqua, Lia Rejane Müller; Cammarota, Martín Pablo
Object recognition memory (ORM) confers the ability to discriminate the familiarity of previously encountered items. Reconsolidation is the process by which reactivated memories become labile and susceptible to modifications. The hippocampus is specifically engaged in reconsolidation to integrate new information into the original ORM through a mechanism involving activation of brain-derived neurotrophic factor (BDNF) signaling and induction of LTP. It is known that BDNF can control LTP maintenance through protein kinase Mζ (PKMζ), an atypical protein kinase C isoform that is thought to sustain memory storage by modulating glutamatergic neurotransmission. However, the potential involvement of PKMζ in ORM reconsolidation has never been studied. Using a novel ORM task combined with pharmacological, biochemical, and electrophysiological tools, we found that hippocampal PKMζ is essential to update ORM through reconsolidation, but not to maintain the inactive recognition memory trace stored over time, in adult male Wistar rats. Our results also indicate that hippocampal PKMζ acts downstream of BDNF and controls AMPAR synaptic insertion to elicit reconsolidation and suggest that blocking PKMζ activity during this process deletes active ORM.SIGNIFICANCE STATEMENT Object recognition memory (ORM) is essential to remember facts and events. Reconsolidation integrates new information into ORM through changes in hippocampal plasticity and brain-derived neurotrophic factor (BDNF) signaling. In turn, BDNF enhances synaptic efficacy through protein kinase Mζ (PKMζ), which might preserve memory. Here, we present evidence that hippocampal PKMζ acts downstream of BDNF to regulate AMPAR recycling during ORM reconsolidation and show that this kinase is essential to update the reactivated recognition memory trace, but not to consolidate or maintain an inactive ORM. We also demonstrate that the amnesia provoked by disrupting ORM reconsolidation through PKMζ inhibition is due to memory erasure and not to retrieval failure.

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Navegando por Autor "Radiske, Andressa"