Impact of serotonin transporter deficiency on parvalbumin- and neuropeptide Y-producing interneurons of the basolateral amygdala
Hyperactivity of the basolateral amygdaloid nuclear complex (BLA) is a hallmark of anxiety-related disorders in humans. Excitation of BLA projection neurons (PN) is fine-tuned by inhibitory interneurons (INs). Monoaminergic afferents to the BLA modulate PN and IN activity. In the present study, BLA-INs immunoreactive(ir) for parvalbumin (PV) or neuropeptide Y (NPY) and their interrelations with serotonergic and catecholaminergic afferents were analyzed in wildtype (WT) and serotonin transporter knockout (5-HTT KO) mice, a model for anxiety- and stress-related disorders. In WT mice, PV- and NPY-ir INs fall into morphological subgroups which possess perisomatic appositions by serotonergic and tyrosine hydroxylase-ir afferents. Dual immunolabeling shows no colocalization of PV and NPY. NPY/somatostatin(SOM) dual labeling documents colocalization of the peptides in some neurons, and single labeling for NPY or SOM in others. These features appear largely preserved in 5-HTT KO mice. However, quantification of PV- and NPY-ir neurons documents a reduction in number and density of NPY-ir neurons throughout the rostrocaudal extent of the amygdala in 5-HTT KO mice. PV-ir neurons remain unchanged. Quantitative PCR shows increased expression of Npy receptor 2, Som receptor 4, and corticotropin releasing factor receptor 1 in the BLA of 5-HTT KO mice. mRNA for the three peptides is unchanged, indicating that it may be NPY propeptide translation which is reduced in 5-HTT KO mice. Taken together, the results document an effect of life-long serotonin imbalance on the BLA NPY-system, which may contribute to previously observed morphological alterations in BLA PNs and increased anxiety-like behavior in 5-HTT KO mice.