Hyperactive ACC-MDT Pathway Suppresses Prepulse Inhibition in Mice.
Schizophr Bull
; 47(1): 31-43, 2021 01 23.
Article
en En
| MEDLINE
| ID: mdl-32621612
ABSTRACT
Altered prepulse inhibition (PPI) is an endophenotype associated with multiple brain disorders, including schizophrenia. Circuit mechanisms that regulate PPI have been suggested, but none has been demonstrated through direct manipulations. IRSp53 is an abundant excitatory postsynaptic scaffold implicated in schizophrenia, autism spectrum disorders, and attention-deficit/hyperactivity disorder. We found that mice lacking IRSp53 in cortical excitatory neurons display decreased PPI. IRSp53-mutant layer 6 cortical neurons in the anterior cingulate cortex (ACC) displayed decreased excitatory synaptic input but markedly increased neuronal excitability, which was associated with excessive excitatory synaptic input in downstream mediodorsal thalamic (MDT) neurons. Importantly, chemogenetic inhibition of mutant neurons projecting to MDT normalized the decreased PPI and increased excitatory synaptic input onto MDT neurons. In addition, chemogenetic activation of MDT-projecting layer 6 neurons in the ACC decreased PPI in wild-type mice. These results suggest that the hyperactive ACC-MDT pathway suppresses PPI in wild-type and IRSp53-mutant mice.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Esquizofrenia
/
Núcleo Talámico Mediodorsal
/
Inhibición Prepulso
/
Giro del Cíngulo
/
Neuronas
Límite:
Animals
Idioma:
En
Revista:
Schizophr Bull
Año:
2021
Tipo del documento:
Article
País de afiliación:
Corea del Sur