p75NGFR mediates death of cholinergic neurons during postnatal development of the neostriatum in mice.

We have previously shown that p75 nerve growth factor receptor (p75NGFR) mediates apoptosis of approximately 25% of the cholinergic basal forebrain neurons in normal control mice between postnatal day 6 and 15, but only of cholinergic neurons that lacked the nerve growth factor receptor TrkA. Here, we investigated whether and when the cholinergic neurons of the neostriatum, which express TrkA and p75NGFR during early postnatal times, undergo p75NGFR-mediated death. The cholinergic neurons in the lateral neostriatal regions expressed choline acetyltransferase (ChAT) earlier (postnatal day 3-6) than those of the medial regions and TrkA appeared before ChAT in all regions. Between postnatal day 6 and 10, approximately 40% of the ChAT-positive neurons in the most lateral regions disappeared in control mice but not in p75NGFR-deficient mice. During this time, the neostriatum of control, but not p75NGFR-deficient, mice contained many apoptotic cells. This suggests that, similar to the cholinergic neurons of the basal forebrain, the neostriatal cholinergic neurons of control mice die and that this process is mediated by p75NGFR. However, the roles of p75NGFR and TrkA appear to be more complicated in the neostriatum where relatively few neurons express p75NGFR during the death phase (and predominantly in the lateral neostriatum where the neuronal loss is greatest), and TrkA-positive as well as TrkA-negative neurons may be lost.