Dual Role of an mps-2/KCNE-Dependent Pathway in Long-Term Memory and Age-Dependent Memory Decline.
Curr Biol
; 31(3): 527-539.e7, 2021 02 08.
Article
em En
| MEDLINE
| ID: mdl-33259792
ABSTRACT
Activity-dependent persistent changes in neuronal intrinsic excitability and synaptic strength are underlying learning and memory. Voltage-gated potassium (Kv) channels are potential regulators of memory and may be linked to age-dependent neuronal disfunction. MinK-related peptides (MiRPs) are conserved transmembrane proteins modulating Kv channels; however, their possible role in the regulation of memory and age-dependent memory decline are unknown. Here, we show that, in C. elegans, mps-2 is the sole member of the MiRP family that controls exclusively long-term associative memory (LTAM) in AVA neuron. In addition, we demonstrate that mps-2 also plays a critical role in age-dependent memory decline. In young adult worms, mps-2 is transcriptionally upregulated by CRH-1/cyclic AMP (cAMP)-response-binding protein (CREB) during LTAM, although the mps-2 baseline expression is CREB independent and instead, during aging, relies on nhr-66, which acts as an age-dependent repressor. Deletion of nhr-66 or its binding element in the mps-2 promoter prevents age-dependent transcriptional repression of mps-2 and memory decline. Finally, MPS-2 acts through the modulation of the Kv2.1/KVS-3 and Kv2.2/KVS-4 heteromeric potassium channels. Altogether, we describe a conserved MPS-2/KVS-3/KVS-4 pathway essential for LTAM and also for a programmed control of physiological age-dependent memory decline.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Memória de Longo Prazo
/
Transtornos da Memória
Limite:
Animals
Idioma:
En
Revista:
Curr Biol
Assunto da revista:
BIOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article