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GFRα‐1 mRNA in dopaminergic and nondopaminergic neurons in the substantia nigra and ventral tegmental area
Author(s) -
Sarabi Arezou,
Hoffer Barry J.,
Olson Lars,
Morales Marisela
Publication year - 2001
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.1400
Subject(s) - substantia nigra , pars compacta , ventral tegmental area , glial cell line derived neurotrophic factor , midbrain , biology , dopaminergic , tyrosine hydroxylase , dopamine , neuroscience , pars reticulata , gabaergic , medicine , endocrinology , neurotrophic factors , inhibitory postsynaptic potential , central nervous system , biochemistry , receptor
Glial cell line‐derived neurotrophic factor (GDNF) is a survival factor for several types of neurons, including dopaminergic (DAergic) neurons. GDNF binds with high affinity to the GDNF family receptor α‐1 (GFRα‐1), which is highly expressed in the midbrain. Using anatomical and lesion techniques, we demonstrated that GFRα‐1 was expressed in DAergic and non‐DAergic neurons in the rat midbrain. Immunohistochemical characterization of GFRα‐1‐expressing neurons indicated that most of the neurons that were immunopositive for the DAergic marker tyrosine hydroxylase (TH) expressed GFRα‐1 in the substantia nigra pars compacta (SNC). In contrast, fewer TH‐containing neurons expressed GFRα‐1 in the substantia nigra pars reticulata (SNR) and the ventral tegmental area (VTA). Depletion of GFRα‐1/TH neurons was observed in the SNC following treatment with the neurotoxin 6‐hydroxydopamine (6‐OHDA); however, GFRα‐1 expression remained in some neurons located in the SNR. The γ‐aminobutyric acid (GABA)ergic nature of GFRα‐1‐expressing neurons located in the SNR, which were resistant to (6‐hydroxydopamine) 6‐OHDA, was established by their expression of glutamic acid decarboxylase (GAD; the synthesizing enzyme for GABA). Further analysis indicated that coexpression of GFRα‐1 and GAD varied in a rostrocaudal gradient in the SNR, substantia nigra pars lateralis (SNL), and VTA. Midbrain DAergic and GABAergic neurons have been previously classified according to their Ca 2+ binding protein (CaBP) content; thus, we also sought to investigate the proportion of midbrain GFRα‐1‐expressing neurons containing parvalbumin (PV), calbindin (CB), and calretinin (CR) in the midbrain. Although GFRα‐1 expression was found mainly in CB‐ and CR‐immunoreactive neurons, it was rarely observed in PV‐immunolabeled neurons. Analysis of the proportion of GFRα‐1‐expressing neurons for each CaBP subpopulation indicated the coexistence of GFRα‐1 with CR in the VTA and all subdivisions of the SN; double‐labeled GFRα‐1/CR neurons were distributed in the SNC, SNR, SNL, and VTA. GFRα‐1/CB neurons were also detected in the SNC, SNL, and VTA. Expression of GFRα‐1 in DAergic and non‐DAergic neurons in the rat SN and VTA suggests that GDNF, via GFRα‐1, might modulate DAergic and GABAergic functions in the nigrostriatal, mesolimbic, and nigrothalamic circuits of the adult rat. J. Comp. Neurol. 441:106–117, 2001. Published 2001 Wiley‐Liss, Inc.