Development of neuronal activity and activity-dependent expression of brain-derived neurotrophic factor mRNA in organotypic cultures of rat visual cortex

We have analyzed in organotypic rat visual cortex cultures the way in which expression of brain-derived neurotrophic factor (BDNF) mRNA depends on syn aptically generated spontaneous bioelectric activity (SBA) as monitored by recordings of pyramidal cells. SEA was initially low, but from the fourth w eek onwards 83% of the neurons fired action potentials at 0.2-1.2 impulses/ s in a well-balanced state of excitation and inhibition. BDNF mRNA expressi on increased during the second week to a level surprisingly similar to the adult visual cortex in vivo, despite the fact that activity rates in vitro were similar to 10-fold lower than rates reported in vivo. Thus, SEA genera ted by a cortical neuronal network in the absence of sensory input is suffi cient to elicit and maintain BDNF expression. The transient BDNF peak occur ring after eye opening in vivo did not occur in vitro. A blockade of SEA se ems not to alter the expression of neurotrophin (NT)-3 and -4/5, and tyrosi ne kinase receptor C and B mRNA. However, BDNF expression remained extremel y low. A recovery of SEA after a period of blockade concurred with a transi ent hyperexcitability. BDNF immediately increased, driven by calcium influx through voltage-gated channels in synergy with NMDA receptors. Expression transiently reached high levels in neurons of supragranular layers. Infragr anular neurons, although firing action potentials, recovered BDNF expressio n much slower. After 5 days in vitro recovery, the network had de novo esta blished a balanced state of excitation and inhibition. Distribution and exp ression level of BDNF mRNA had returned to central. Even in 'adult' culture s an acute blockade of SEA downregulated BDNF, and a subsequent recovery of SEA restored BDNF expression. We conclude that BDNF mRNA expression depend s on and responds with a fast kinetic to changes of the SEA. Steady-state l evels do not depend on the absolute levels of activity, but more likely on the balance between excitation and inhibition, suggesting a role for BDNF i n activity homeostasis.