Activity-dependent activation of TrkB neurotrophin receptors in the adult CNS

In this paper we have investigated the hypothesis that neural activity caus es rapid activation of TrkB neurotrophin receptors in the adult mammalian C NS. These studies demonstrate that kainic acid-induced seizures led to a ra pid and transient activation of TrkB receptors in the cortex. Subcellular f ractionation demonstrated that these activated Trk receptors were preferent ially enriched in the synaptosomal membrane fraction that also contained po stsynaptic glutamate receptors. The fast activation of synaptic TrkB recept ors could be duplicated in isolated cortical synaptosomes with KCl, presuma bly as a consequence of depolarization-induced BDNF release. Importantly, T rkB activation was also observed following pharmacological activation of br ain-stem noradrenergic neurons, which synthesize and anterogradely transpor t BDNF; treatment with yohimbine led to activation of cortical TrkB recepto rs within 30 min. Pharmacological blockade of the postsynaptic alpha 1-adre nergic receptors with prazosin only partially inhibited this effect, sugges ting that the TrkB activation was partially due to a direct effect on posts ynaptic cortical neurons. Together, these data support the hypothesis that activity causes release of BDNF from presynaptic terminals, resulting in a rapid activation of postsynaptic TrkB receptors. This activity-dependent Tr kB activation could play a major role in morphological growth and remodelli ng in both the developing and mature nervous systems.