Navegando por Autor "Gonzalez, Maria Carolina"

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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.
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
Estresse pré-natal: efeitos em longo prazo no comportamento e no balanço dos metabólitos do triptofano
(Universidade Federal do Rio Grande do Norte, 2020-09-24) Moura, Clarissa de Almeida; Gavioli, Elaine Cristina; ; http://lattes.cnpq.br/1759328747578795; ; http://lattes.cnpq.br/3959260293234744; Belchior, Hindiael Aeraf; ; http://lattes.cnpq.br/2815729240392635; Anomal, Renata Figueiredo; ; http://lattes.cnpq.br/6437989445919424; Zanoveli, Janaina Menezes; ; http://lattes.cnpq.br/2879707811631626; Gonzalez, Maria Carolina; ; http://lattes.cnpq.br/4560931690994322
O estresse pré-natal (EPN) interfere diretamente na programação fetal, princípio pelo qual o ambiente endócrino e metabólico da mãe pode gerar consequências em longo prazo na prole adulta. Dentre as potenciais vias neuroquímicas afetadas pelo EPN, destaca-se a via das quinureninas, principal via de metabolismo do triptofano, relacionada à diversos transtornos psiquiátricos, mas pouco se sabe sobre sua relação com o EPN. Este estudo buscou investigar as consequências comportamentais e neuroquímicas do EPN, com ênfase nas monoaminas e nos metabólitos da via das quinureninas, na prole adulta de camundongos expostos ao EPN. Fêmeas prenhas de camundongos Swiss foram submetidas ao modelo de estresse por contenção associado com luz intensa três vezes por dia durante a última semana de gestação (dia 14-21). A prole adulta de machos e fêmeas submetida à EPN passou por testes comportamentais, incluindo: campo aberto, tarefa de reconhecimento de objetos, labirinto em cruz elevado, interação social e teste de suspensão pela cauda. Para a etapa neuroquímica, a prole adulta foi eutanasiada e seus encéfalos dissecados a fim de quantificar os níveis de triptofano, ácido quinolínico (QA), quinurenina, ácido 5-hidroxiindol acético (5-HIAA), serotonina (5-HT), dopamina e noradrenalina no hipocampo e no tronco encefálico, através da técnica de espectrometria de massa. O córtex pré-frontal (CPF) e hipocampo da prole foram também dissecados, a fim de avaliar a expressão gênica das seguintes enzimas: indoleamina 2,3-dioxigenase (IDO), quinurenina monoxigenase (KMO) e quinurenina-aminotransferase 3 (KYAT3), através da técnica de PCR em tempo real. Os resultados revelaram que a prole adulta submetida ao EPN apresentou: (1) prejuízo na tarefa de reconhecimento de objetos na prole macho e fêmea, com esta última sendo associado ao ciclo estral; (2) hiperatividade da prole macho, acessada pela maior distância total percorrida em campo aberto, bem como maior tempo de permanência nos braços fechados no teste de labirinto em cruz elevado, sugerindo fenótipo ansioso, sem alterações nos níveis de monoaminas, porém com alterações nos metabólitos da via das quinureninas, definidos por níveis mais altos de QA no hipocampo e no tronco encefálico e níveis mais altos de quinurenina e triptofano exclusivamente no hipocampo, (3) aumento de imobilidade no teste de suspensão pela cauda prole fêmea, sugerindo perfil depressivo, influenciado pelas fases do ciclo estral, e associado a níveis mais baixos de 5-HT no hipocampo e maior atividade de 5-HT no hipocampo e no tronco encefálico, (4) alteração na expressão gênica de enzimas relacionadas com a via das quinureninas, de forma que fêmeas EPN tiveram maior expressão de KYAT3 no hipocampo e de IDO no CPF, enquanto a prole macho apresentou níveis reduzidos de KMO no CPF. Em conclusão, este estudo revelou um perfil comportamental e neuroquímico sexo dependente como consequência do EPN tardio na prole de camundongos, avaliando como ponto chave o balanço de metabólitos do triptofano.
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
Investigação do padrão de expressão da CaMKII após o aprendizado na tarefa de reconhecimento de objetos
(Universidade Federal do Rio Grande do Norte, 2024-08-08) Silva, Líginy Monique Rodrigues; Rossato, Janine Inez; http://lattes.cnpq.br/8136970112250481; http://lattes.cnpq.br/8570340476726050; Giordani , Raquel Brandt; http://lattes.cnpq.br/5032750980466610; Gonzalez, Maria Carolina; http://lattes.cnpq.br/4560931690994322
A memória é um fenômeno complexo e vital para a cognição humana e animal, permitindo a retenção e a recuperação de informações essenciais para o aprendizado e a tomada de decisões. A experiência mental da memória é subjetiva e, portanto, não é possível avaliá-la diretamente em espécies não humanas, com isso tarefas que empregam modelos animais, como a tarefa de reconhecimento de objetos podem ser empregadas. Esse modelo é amplamente estudado para avaliar memórias declarativas, que são as mais afetadas nas doenças degenerativas, como a Doença de Alzheimer - DA. Os estudos indicam que o sistema hipocampal desempenha um papel chave durante o processamento da memória de reconhecimento. A homeostase do Ca2+ parece estar em desequilíbrio na DA, levando ao prejuízo cognitivo acentuado. Os níveis intracelulares dos íons Ca2+ regulam algumas proteínas que desempenham papel chave no processamento mnemônico, como a CaMKII, que está particularmente enriquecida no hipocampo e localizada na densidade pós-sináptica. Portanto, o isolamento e quantificação de proteínas sinápticas é uma técnica necessária e útil para obter informações sobre as formas como os neurônios respondem aos estímulos e alteram a eficácia sináptica. Nosso trabalho mostrou que nosso protocolo de isolamento sináptico gera uma fração sinaptossomal crua enriquecida com proteínas da densidade pós-sináptica; e que, através da utilização dessa fração observamos um aumento da expressão da isoforma fosforilada, pCaMKII, Thr286, logo após o treinamento na tarefa de reconhecimento de objetos.
Mecanismos neurais envolvidos na formação, atualização e integração da memória de reconhecimento de objetos
(Universidade Federal do Rio Grande do Norte, 2023-07-31) Gonzalez, Maria Carolina; Cammarota, Martin Pablo; https://orcid.org/0000-0001-9741-5074; http://lattes.cnpq.br/4888317387600937; https://orcid.org/0000-0003-4685-6739; http://lattes.cnpq.br/4560931690994322; Cunha, Cláudio da; Bertoglio, Leandro José; Moraes, Márcio Flávio Dutra; Maciel, Sérgio Tulio Neuenschwander
As novas memórias são instáveis e suscetíveis a interferência, e apenas algumas delas são armazenadas de forma duradoura por meio da consolidação, um processo de estabilização dependente da síntese de proteínas. As memórias consolidadas podem retornar a um estado de instabilidade quando evocadas e, para persistir, devem ser reconsolidadas. A reconsolidação também é um processo de estabilização que depende de síntese proteica, mas não é uma mera repetição da consolidação inicial. A relevância biológica da reconsolidação ainda é debatida, mas evidências experimentais sugerem que sua função é atualizar memórias já consolidadas com novas informações adquiridas durante sua evocação. A memória de reconhecimento de objetos (MRO) é um componente da memória declarativa que permite lembrar as características de itens familiares e discriminá-los dos novos. Neste trabalho, utilizamos ratos Wistar para confirmar a participação do hipocampo dorsal na consolidação da MRO, estudar os mecanismos moleculares envolvidos neste processo e mostrar que o mesmo resulta no armazenamento de representações independentes. Confirmamos também que a reconsolidação da MRO depende do hipocampo unicamente quando sua reativação acontece simultaneamente com a detecção de novidade. Posteriormente, demonstramos que a reconsolidação da MRO induzida pela apresentação de um objeto desconhecido medeia a associação da informação pertinente a esse objeto com a memória original por meio de um mecanismo que requer a desestabilização prévia da memória reativada. Essa desestabilização é regulada pela atividade do receptor de dopamina D1/D5 no hipocampo dorsal, e a subsequente restabilização do traço atualizado envolve a expressão de Zif268 e mecanismos de plasticidade sináptica que são controlados pelo BDNF e a reciclagem de receptores AMPA regulada pela proteína quinase M zeta (PKMζ). Mostramos também que a desestabilização da MRO está associada ao acoplamento faseamplitude entre os ritmos teta e gama hipocampais, e que a indução artificial desse padrão oscilatório desestabiliza memórias que normalmente são resistentes à reconsolidação. Por fim, mostramos que a amnésia causada pelo bloqueio da reconsolidação não se deve a falhas na sua evocação, mas sim à eliminação da MRO em questão, e que as informações que fazem parte de uma rede de conhecimento declarativo podem ser reativadas indiretamente, tornando-se suscetíveis a modificação.
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
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 da PKA cortical na formação da memória de reconhecimento de objetos
(Universidade Federal do Rio Grande do Norte, 2023-09-28) Araújo, Raquel Lúcia Souto de; Cammarota, Martin Pablo; Rossato, Janine Inez; https://orcid.org/0000-0002-7980-5842; http://lattes.cnpq.br/8136970112250481; https://orcid.org/0000-0001-9741-5074; http://lattes.cnpq.br/4888317387600937; http://lattes.cnpq.br/0623474419062785; Laplagne, Diego Andres; Gonzalez, Maria Carolina
Memória de reconhecimento é um componente central das memórias declarativas. Falhas no processamento dessas memórias acarretam consequências severas que caracterizam os sintomas iniciais em pacientes com declínio cognitivo, como a Doença de Alzheimer. A tarefa de reconhecimento de objeto novo é utilizada para avaliar os mecanismos moleculares envolvidos no processamento de memória de reconhecimento que requer detecção de novidade no ambiente. Diferentes regiões do cérebro são necessárias para discriminar objetos. O córtex pré-frontal medial (mPFC) e o hipocampo desempenham funções distintas durante o processamento deste tipo de memória. A dopamina é importante para a detecção de novidade e a sinalização mediada pela ativação de receptores D1/D5 é mediada pela proteína cinase ativada por AMPc, PKA. O objetivo deste trabalho foi avaliar o papel da PKA cortical na formação da memória de reconhecimento de objetos em ratos. Foram utilizados ratos Wistar adultos e de meia idade, machos e fêmeas, implantados bilateralmente com cânulas no mPFC. Nossos resultados demonstram que, em ratos, a consolidação da memória de reconhecimento de objetos de longa duração requer a ativação da PKA no mPFC logo após o treino. Sexo, idade e período do ciclo claro/escuro não interferem na formação deste tipo de memória e a inibição da PKA nestes indivíduos também induz amnésia. A inibição da PKA também impede a formação da memória de reconhecimento de objetos de curta duração. Com esses achados, podemos inferir que a PKA no mPFC é fundamental para a formação das memórias de reconhecimento de objetos.
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.
Prior learning of relevant non-aversive information is a boundary condition for avoidance memory reconsolidation in the rat hippocampus
(2017-09-08) Radiske, Andressa; Gonzalez, Maria Carolina; Conde-Ocaziones, Sergio; Feitosa, Anatildes; Köhler, Cristiano A.; Bevilaqua, Lia Rejane Müller; Cammarota, Martín Pablo
Reactivated memories can be modified during reconsolidation, making this process a potential therapeutic target for post-traumatic stress disorder (PTSD), a mental illness characterized by the recurring avoidance of situations that evoke trauma-related fears. However, avoidance memory reconsolidation depends on a set of still loosely defined boundary conditions, limiting the translational value of basic research. In particular, the involvement of the hippocampus in fear-motivated avoidance memory reconsolidation remains controversial. Combining behavioral and electrophysiological analyses in male Wistar rats, we found that previous learning of relevant non-aversive information is essential to elicit the participation of the hippocampus in avoidance memory reconsolidation, which is associated with an increase in theta and gamma oscillations power and cross-frequency coupling in dorsal CA1 during reactivation of the avoidance response. Our results indicate that the hippocampus is involved in memory reconsolidation only when reactivation results in contradictory representations regarding the consequences of avoidance, and suggest that robust nesting of hippocampal theta-gamma rhythms at the time of retrieval is a specific reconsolidation marker.
Reactivation-dependent amnesia for object recognition memory is contingent on hippocampal theta-gamma coupling during recall
(Cold Spring Harbor Laboratory, 2022-01) Gonzalez, Maria Carolina; Radiske, Andressa; Ocazionez, Sergio Andrés Conde; Rossato, Janine Inez; Bevilaqua, Lia Rejane Muller; Cammarota, Martín Pablo
Hippocampal dopamine D1/D5 receptor-dependent destabilization is necessary for object recognition memory (ORM) updating through reconsolidation. Dopamine also regulates hippocampal theta and gamma oscillations, which are involved in novelty and memory processing. We found that, in adult male rats, ORM recall in the presence of a novel object, but not in the presence of a familiar one, triggers hippocampal theta-gamma coupling. Hippocampal theta-gamma coupling (hPAC) does not happen when ORM destabilization is prevented by blocking D1/D5 receptors, but artificial hPAC generation during recall in the presence of a familiar object enables the amnesic effect of reconsolidation inhibitors. Therefore, hPAC controls ORM destabilization, and its modulation could increase reconsolidation-based psychotherapy efficacy
Recognition memory reconsolidation requires hippocampal Zif268
(2019-11-12) Gonzalez, Maria Carolina; Rossato, Janine I.; Radiske, Andressa; Reis, Marina Pádua; Cammarota, Martín Pablo
Object recognition memory (ORM) serves to distinguish familiar items from novel ones. Reconsolidation is the process by which active memories are updated. The hippocampus is engaged in ORM reconsolidation through a mechanism involving induction of long-term potentiation (LTP). The transcription factor Zif268 is essential for hippocampal LTP maintenance and has been frequently associated with memory processes. However, its possible involvement in ORM reconsolidation has not been determined conclusively. Using Zif268 antisense oligonucleotides in combination with behavioural, biochemical and electrophysiological tools in rats, we found that hippocampal Zif268 is necessary to update ORM through reconsolidation but not to retrieve it or keep it stored. Our results also suggest that knocking down hippocampal Zif268 during ORM reconsolidation deletes the active recognition memory trace.

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Navegando por Autor "Gonzalez, Maria Carolina"