PKMZETA MAINTAINS REMOTE CONTEXTUAL FEAR MEMORY BY INHIBITING GLUA2-DEPENDENT AMPA RECEPTOR ENDOCYTOSIS IN THE PRELIMBIC CORTEX

Thais Fernanda Dalferth; Lucas A. Marcondes; Jociane De Carvalho Myskiw; Eduarda Godfried Nachtigall; Cristiane Furini

Título do Trabalho

Autores

Thais Fernanda Dalferth
Lucas A. Marcondes
Jociane De Carvalho Myskiw
Eduarda Godfried Nachtigall
Cristiane Furini

Modalidade

Resumo simples

Área temática

Aprendizagem e Neurodesenvolvimento

Data de Publicação

17/01/2023

País da Publicação

Brasil

Idioma da Publicação

Português

Página do Trabalho

https://www.even3.com.br/anais/consbran2022/584390-pkmzeta-maintains-remote-contextual-fear-memory-by-inhibiting-glua2-dependent-ampa-receptor-endocytosis-in-the-pr

ISBN

978-85-5722-539-8

Palavras-Chave

Memory; contextual fear conditioning; persistence, PKMzeta; prelimbic cortex

Resumo

Fear memories allow animals to recognize and respond appropriately to dangerous situations. The prelimbic cortex (PrL) is crucial in the circuit that encodes the memory of contextual fear conditioning (CFC), and its activity is central to the expression of fear memory long term. However, although PrL is involved in CFC memory storage, the molecular mechanisms underlying its maintenance are still unclear. Thus, since protein kinase M zeta (PKMzeta) is a persistently active enzyme that has been shown to maintain many forms of memory by inhibiting the endocytosis of AMPA receptors containing GluA2, we hypothesized that the action of PKMzeta is a mechanism responsible for the maintenance of CFC memory in PrL. To test this hypothesis, we used adult male Wistar rats (n = 7-1 per group), which were anesthetized with intraperitoneal injections of ketamine (75 mg/kg) and xylazine (10 mg/kg) and submitted to stereotaxic surgery for implantation of cannulae bilaterally, directed 1.0 mm above the prelimbic cortex. After recovery, the animals were subjected to a CFC paradigm, composed of a training session (Tr) consisting of 2 min of habituation, followed by 3 stimuli 0.7 mA/2 s in the paws with an interval of 30 s and we administered intra-PrL infusions of the inhibitor of PKMzeta ZIP (10 nmol per side), the GluA2-dependent endocytosis inhibitor GluA23Y (100 pmol per side) or the inactive peptide GluA23Y(s) (100 pmol per side). Twenty-four hours later, the animals were replaced in the device for a long-term memory retention test (3 minutes, without electrical stimulation). Control groups received sterile saline solution (Vehicle). At the procedure, the immobility time of the animals was evaluated. The data were analyzed by Two-way ANOVA, followed by the Bonferroni test. Data expressed as mean ± S.E.M. The P value is p<0.05. CEUA/PUCRS approval: 9421. As a result of the experiments, we found that acute inhibition of GluA2-dependent AMPAR endocytosis in the PrL does not affect recent or remote contextual fear memory maintenance. Also, PKMzeta inhibition in the PrL does not impair the maintenance of recent contextual fear memory. However, we found that inhibition of prelimbic PKMzeta at a remote time point disrupts contextual fear memory maintenance, and that blocking GluA2-dependent removal of AMPARs prevents this impairment. Our results confirm the central role of PrL in fear memory and identify PKMzeta induced inhibition of GluA2-containing AMPAR endocytosis as a key mechanism governing remote contextual fear memory maintenance. In conclusion, our study confirms PrL as a cardinal to the remote fear memory storage mechanism and identifies the AMPAR endocytosis site of PKMzeta-driven inhibition as a molecular underlying the persistence of the remote fear contextual memory trait in this region. These findings may help to understand the differential contribution of the prelimbic cortex to fear memories over time and also to elucidate the molecular underpinnings of memory persistence.

Título do Evento: I Congresso Sul-Brasileiro em Neurociências
Título dos Anais do Evento: Anais do I Congresso Sul-Brasileiro em Neurociências
Nome da Editora: Even3
Meio de Divulgação: Meio Digital

Como citar

DALFERTH, Thais Fernanda et al.. PKMZETA MAINTAINS REMOTE CONTEXTUAL FEAR MEMORY BY INHIBITING GLUA2-DEPENDENT AMPA RECEPTOR ENDOCYTOSIS IN THE PRELIMBIC CORTEX.. In: . Disponível em: https//www.even3.com.br/anais/consbran2022/584390-PKMZETA-MAINTAINS-REMOTE-CONTEXTUAL-FEAR-MEMORY-BY-INHIBITING-GLUA2-DEPENDENT-AMPA-RECEPTOR-ENDOCYTOSIS-IN-THE-PR. Acesso em: 25/06/2025