Developmental changes in the response of trigeminal neurons to neurotrophins: influence of birthdate and the ganglion environment

Abstract

Previous studies have shown that most neurons in cultures established during the early stages of neurogenesis in the embryonic mouse trigeminal ganglion are supported by BDNF whereas most neurons cultured from older ganglia survive with NGF. To ascertain to what extent these developmental changes in neurotrophin responsiveness result from separate phases of generation of BDNF- and NGF-responsive neurons or from a developmental switch in the response of neurons from BDNF to NGF, we administered BrdU to pregnant mice at different stages of gestation to identify neurons born at different times and studied the survival of labelled neurons in dissociated cultures established shortly after BrdU administration. Most early-generated neurons responded to BDNF, neurons generated at intermediate times responded to both factors and late-generated neurons responded to NGF, indicating that there are overlapping phases in the generation of BDNF- and NGF-responsive neurons and that late-generated neurons do not switch responsiveness from BDNF to NGF. To ascertain if early-generated neurons do switch their response to neurotrophins during development, we used repeated BrdU injection to label all neurons generated after an early stage in neurogenesis and studied the neurotrophin responsiveness of the unlabelled neurons in cultures established after neurogenesis had ceased. The response of these early-generated neurons had decreased to BDNF and increased to NGF, indicating that at least a proportion of early-generated neurons switch responsiveness to neurotrophins in vivo. Because early-generated neurons do not switch responsiveness from BDNF to NGF in long-term dissociated cultures, we cultured early trigeminal ganglion explants with and without their targets for 24 hours before establishing dissociated cultures. This period of explant culture was sufficient to enable many early-generated neurons to switch their response from BDNF to NGF and this switch occurred irrespective of presence of target tissue. Our findings conclusively demonstrate for the first time that individual neurons switch their neurotrophin requirements during development and that this switch depends on cell interactions within the ganglion. In addition, we show that there are overlapping phases in the generation of BDNF- and NGF-responsive neurons in the trigeminal ganglion.