Neurotrophin receptor heterozygosity causes deficits in catecholaminergic innervation of amygdala and hippocampus in aged mice.

We have recently shown that aged mice with haploinsufficiencies for the neurotrophin receptors trkB, trkC or both, trkB and trkC, display reduced cell numbers in the substantia nigra and in the dentate gyrus, but not in the amygdala. Moreover, both hippocampus and amygdala contain increased numbers of degenerated axonal fragments. Consistent with this observation and the expression of trkB and trkC by midbrain dopaminergic neurons, we show now that heterozygous deletion of the trkB or/and trkC receptor genes significantly reduces catecholaminergic, tyrosine hydroxylase (TH-) positive fiber densities in the hippocampus and amygdala mainly in aged (21-23 month old) mice. In the amygdala the phenotype was restricted to the lateral and basolateral nucleus of the amygdala. In adult (6 month old) mice, reductions in catecholaminergic fiber densities were only found in the hippocampal area CA3 and the dentate gyrus of heterozygous trkB and trkB/C mice. Our observations suggest that signaling through trkB and trkC neurotrophin receptors is important for the maintenance of the catecholaminergic innervation of two limbic key regions, the hippocampus and amygdala.