An activity-dependent neurotrophin-3 autocrine loop regulates the phenotype of developing hippocampal pyramidal neurons before target contact.
J Neurosci
; 21(22): 8789-97, 2001 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-11698591
ABSTRACT
Neurotrophin-3 (NT-3), its cognate receptor trkC, and voltage-gated calcium channels are coexpressed by embryonic pyramidal neurons before target contact, but their functions at this stage of development are still unclear. We show here that, in vitro, anti-NT-3 and anti-trkC antibodies blocked the increase, and NT-3 reversed the decrease in the number of calbindin-D(28k)-positive pyramidal neurons induced by, respectively, calcium channel activations and blockades. Similar results were obtained with single-neuron microcultures. In addition, voltage-gated calcium channel inhibition downregulates the extracellular levels of NT-3 in high-density cultures. Moreover, electrophysiological experiments in single-cell cultures reveal a tetrodotoxin-sensitive spontaneous electrical activity allowing voltage-gated calcium channel activation. The mouse NT-3 (-/-) mutation decreases by 40% the number of developing calbindin-D(28k)-positive pyramidal neurons, without affecting neuronal survival, both in vitro and in vivo. Thus, present results strongly support that an activity-dependent autocrine NT-3 loop provides a local, intrinsic mechanism by which, before target contact, hippocampal pyramidal-like neurons may regulate their own differentiation, a role that may be important during early CNS differentiation or after adult target disruption.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Piramidais
/
Comunicação Autócrina
/
Neurotrofina 3
/
Hipocampo
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Neurosci
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
França