Electrophysiological and morphological evidence for a GABAergic nigrostriatal pathway - PubMed (original) (raw)

Electrophysiological and morphological evidence for a GABAergic nigrostriatal pathway

M Rodríguez et al. J Neurosci. 1999.

Abstract

The electrophysiological and neurochemical characteristics of the nondopaminergic nigrostriatal (NO-DA) cells and their functional response to the degeneration of dopaminergic nigrostriatal (DA) cells were studied. Three different criteria were used to identify NO-DA cells: (1) antidromic response to striatal stimulation with an electrophysiological behavior (firing rate, interspike interval variability, and conduction velocity) different from that of DA cells; (2) retrograde labeling after striatal injection of HRP but showing immunonegativity for DA cell markers (tyrosine hydroxylase, calretinin, calbindin-D28k, and cholecystokinin); and (3) resistance to neurotoxic effect of 6-hydroxydomine (6-OHDA). Our results showed that under normal conditions, 5-8% of nigrostriatal neurons are immunoreactive for GABA, glutamic acid decarboxylase, and parvalbumin, markers of GABAergic neurons, a percentage that reached 81-84% after 6-OHDA injection. Electrophysiologically, NO-DA cells showed a behavior similar to that found in other nigral GABAergic (nigrothalamic) cells. In addition, the 6-OHDA degeneration of DA cells induced a modification of their electrophysiological pattern similar to that found in GABAergic nigrothalamic neurons. Taken together, the present data indicate the existence of a small GABAergic nigrostriatal pathway and suggest their involvement in the pathophysiology of Parkinson's disease.

PubMed Disclaimer

Figures

Fig. 1.

Fig. 1.

Electrophysiological identification of NO-DA, DA, and nigrothalamic cells. An example of the spike shape (a–c) and collision test (d–f) in NO-DA, nigrothalamic, and DA cells, respectively, is shown. The antidromic response consisted of the full spike in NO-DA cells (d) and nigrothalamic cells (e) and the initial segment in DA cells (f). Because the antidromic stimulation of DA cells often displays the initial segment but not the somatodendritic component of the spike (spike dissociation), the antidromic spike shown at the top of f is clearly different (somatodendritic component virtually absent) from the spontaneous spike showed at the bottom of_f_. g, Antidromic latency histogram of nigrostriatal cells. Values are expressed as a percentage of the total number of NO-DA (n = 19) or DA (n = 123) recorded neurons. h, Basal activity and conduction velocity of DA and NO-DA nigrostriatal (NS) and nigrothalamic (NT) cells. *p < 0.0001 versus NS DA cells; **p < 0.01 versus NS DA cells. °p < 0.0001 versus NT cells.Arrows in c and d indicate the initial part of the striatal stimulus artifact. Values represent the mean ± SE.

Fig. 2.

Fig. 2.

HRP-TH double labeling after HRP injection in the striatum of unlesioned rats. a, Rostrolateral region of the SN; b, boxed area in_a_; c, caudomedial region of the SN.Arrows in b and c indicate single HRP-stained neurons in focus with double-labeled neurons (arrowheads). Scale bars: a, 200 μm;b, c, 50 μm.

Fig. 3.

Fig. 3.

Mesencephalic distribution of cells projecting to the striatum according to their tyrosine hydroxylase immunoreactivity (n = 10,800 HRP cells). TH(+), Tyrosine hydroxylase-immunopositive cells; TH (−), tyrosine hydroxylase-immunonegative cells.

Fig. 4.

Fig. 4.

Double-labeled neurons for HRP and GAD (a–c), HRP and GABA (d, e), and HRP and PV (f) in the SNr (a, b, d–f) and VTA (c) of unlesioned rats. The arrow in a indicates the neuron shown in b. In c, d, and_f_, arrows indicate double-labeled neurons; arrowheads indicate single immunostained neurons. Scale bars: a, 200 μm; b, f, 20 μm; c–e, 30 μm.

Fig. 5.

Fig. 5.

Distribution of GAD-IR nigrostriatal neurons.a, Example of HRP injection in the striatum.b, Schematic drawing showing the localization of the HRP injection in some representative cases. c, Distribution of GAD-HRP neurons in the SN in two cases. Solid circles_indicate the localization of double-labeled neurons after injection in the lateral half of striatum (shown in a, black area in b). Open circles indicate the localization of double-labeled neurons after injection in the medial half of striatum (shadowed area in_b). Each circle corresponds to three neurons. Modified drawing from Paxinos and Watson (1988). The distance of each section to the interaural line is shown in millimeters.ac, Anterior commissure; cc, corpus callosum; f, fornix; GP, globus pallidus;ic, internal capsule; lv, lateral ventricle; MT, medial terminal nucleus of the accessory optical tract; S, septum; SNl, substantia nigra pars lateralis; St, striatum. Scale bar, 1 mm.

Fig. 6.

Fig. 6.

TH (a–d), CR (e, f), and CB (g, h) immunocytochemistry after 6-OHDA injection in the right medial forebrain bundle and HRP injection in the ipsilateral striatum.a, e, g, Lesioned side; b, f, h, unlesioned side. c, d, Boxed areas in_a_; arrows indicate single HRP-stained neurons. Scale bars: a, b, e–h, 150 μm; c, d, 35 μm.

Fig. 7.

Fig. 7.

Double-labeled neurons for HRP and GAD (a), HRP and GABA (b), and HRP and PV (c, d) in SNr of 6-OHDA lesioned rats.d, Boxed area in c;arrows in b and d indicate double-labeled neurons; arrowhead in _d_indicates a single PV-immunostained neuron. Scale bars: a, b, 20 μm; c, 200 μm; d, 30 μm.

Fig. 8.

Fig. 8.

Percentage of nigrostriatal cells showing TH, CCK, CB, CR, GABA, GAD, and PV immunoreactivity in sham (n = 4200 HRP cells per series) and 6-OHDA-injected (n = 420 HRP cells per series) rats.

Fig. 9.

Fig. 9.

Functional effect of DA cell degeneration on NO-DA and nigrothalamic (NT) cells. *p < 0.05 versus sham-lesioned rats. Values represent the mean ± SE.

Similar articles

Cited by

References

    1. Adams JC. Technical considerations on the use of horseradish peroxidase as a neuronal marker. Neuroscience. 1977;2:141–145. - PubMed
    1. Adams JC. Heavy metal intensification of DAB-based HRP reaction product. J Histochem Cytochem. 1981;29:775. - PubMed
    1. Albin RL, Young AB, Penney JB. The functional anatomy of basal ganglia disorders. Trends Neurosci. 1989;12:366–375. - PubMed
    1. Alexander GE, Crutcher MD. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci. 1990a;13:266–271. - PubMed
    1. Alexander GE, Crutcher MD. Preparation for movement: neural representations of intended direction in three motor areas of the monkey. J Neurophysiol. 1990b;68:945–960. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources