Type VI adenylyl cyclase negatively regulates GluN2B-mediated LTD and spatial reversal learning.
Sci Rep
; 6: 22529, 2016 Mar 02.
Article
em En
| MEDLINE
| ID: mdl-26932446
ABSTRACT
The calcium-sensitive type VI adenylyl cyclase (AC6) is a membrane-bound adenylyl cyclase (AC) that converts ATP to cAMP under stimulation. It is a calcium-inhibited AC and integrates negative inputs from Ca(2+) and multiple other signals to regulate the intracellular cAMP level. In the present study, we demonstrate that AC6 functions upstream of CREB and negatively controls neuronal plasticity in the hippocampus. Genetic removal of AC6 leads to cyclase-independent and N-terminus of AC6 (AC6N)-dependent elevation of CREB expression, and enhances the expression of GluN2B-containing NMDA receptors in hippocampal neurons. Consequently, GluN2B-dependent calcium signaling and excitatory postsynaptic current, long-term depression, and spatial reversal learning are enhanced in the hippocampus of AC6(-/-) mice without altering the gross anatomy of the brain. Together, our results suggest that AC6 negatively regulates neuronal plasticity by modulating the levels of CREB and GluN2B in the hippocampus.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Adenilil Ciclases
/
Receptores de N-Metil-D-Aspartato
/
Depressão Sináptica de Longo Prazo
/
Aprendizagem
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article