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

Previous studies have shown that most neurons in cultures established durin g the early stages of neurogenesis in the embryonic mouse trigeminal gangli on are supported by BDNF whereas most neurons cultured from older ganglia s urvive with NGF To ascertain to what extent these developmental changes in neurotrophin responsiveness result from separate phases of generation of BD NF- and NGF-responsive neurons or from a developmental switch in the respon se of neurons from BDNF to NGF, we administered BrdU to pregnant mice at di fferent stages of gestation to identify neurons born at different times and studied the survival of labelled neurons in dissociated cultures establish ed shortly after BrdU administration, Most early-generated neurons responde d to BDNF, neurons generated at intermediate times responded to both factor s and late-generated neurons responded to NGF, indicating that there are ov erlapping 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 neurotr ophins during development, we used repeated BrdU injection to label all neu rons generated after an early stage in neurogenesis and studied the neurotr ophin responsiveness of the unlabelled neurons in cultures established afte r neurogenesis had ceased. The response of these early-generated neurons ha d decreased to BDNF and increased to NGF, indicating that at least a propor tion of early-generated neurons switch responsiveness to neurotrophins in v ivo. Because early-generated neurons do not switch responsiveness from BDNF to NGF in long-term dissociated cultures, we cultured early trigeminal gan glion explants with and without their targets for 24 hours before establish ing dissociated cultures, This period of explant culture was sufficient to enable many early-generated neurons to switch their response from BDNF to N GF and this switch occurred irrespective of presence of target tissue, Our findings conclusively demonstrate for the first time that individual neuron s switch their neurotrophin requirements during development and that this s witch depends on cell interactions within the ganglion, In addition, we sho w that there are overlapping phases in the generation of BDNF- and NGF-resp onsive neurons in the trigeminal ganglion.