VGLUT3 neurons in median raphe control the efficacy of spatial memory retrieval via ETV4 regulation of VGLUT3 transcription.
Sci China Life Sci
; 65(8): 1590-1607, 2022 08.
Article
em En
| MEDLINE
| ID: mdl-35089530
ABSTRACT
The raphe nucleus is critical for feeding, rewarding and memory. However, how the heterogenous raphe neurons are molecularly and structurally organized to engage their divergent functions remains unknown. Here, we genetically target a subset of neurons expressing VGLUT3. VGLUT3 neurons control the efficacy of spatial memory retrieval by synapsing directly with parvalbumin-expressing GABA interneurons (PGIs) in the dentate gyrus. In a mouse model of Alzheimer's disease (AD mice), VGLUT3âPGIs synaptic transmission is impaired by ETV4 inhibition of VGLUT3 transcription. ETV4 binds to a promoter region of VGLUT3 and activates VGLUT3 transcription in VGLUT3 neurons. Strengthening VGLUT3âPGIs synaptic transmission by ETV4 activation of VGLUT3 transcription upscales the efficacy of spatial memory retrieval in AD mice. This study reports a novel circuit and molecular mechanism underlying the efficacy of spatial memory retrieval via ETV4 inhibition of VGLUT3 transcription and hence provides a promising target for therapeutic intervention of the disease progression.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Vesiculares de Transporte de Glutamato
/
Memória Espacial
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article