Electrophysiological studies of rat substantia nigra neurons in an in vitro slice preparation after middle cerebral artery occlusion

doi:10.1016/S0306-4522(96)00555-6

Neuroscience

Volume 77, Issue 4, 14 February 1997, Pages 1021-1028

https://doi.org/10.1016/S0306-4522(96)00555-6 Get rights and content

Abstract

We studied sequential changes in electrophysiological profiles of the ipsilateral substantia nigra neurons in an in vitro slice preparation obtained from the middle cerebral artery-occluded rats. Histological examination revealed marked atrophy and neurodegeneration in the ipsilateral substantia nigra pars reticulata at 14 days after middle cerebral artery occlusion. Compared with the control group, there was no significant change in electrical membrane properties and synaptic responses of substantia nigra pars reticulata neurons examined at one to two weeks after middle cerebral artery occlusion. On the other hand, there was a significant increase in the input resistance and spontaneous firing rate of substantia nigra pars compacta neurons at 13–16 days after middle cerebral artery occlusion. Furthermore, inhibitory postsynaptic potentials evoked by stimulation of the subthalamus in substantia nigra pars compacta neurons was suppressed at five to eight days after middle cerebral artery occlusion. At the same time excitatory postsynaptic potentials evoked by the subthalamic stimulation was increased. Bath application of bicuculline methiodide (50 μM), a GABA_A receptor antagonist, significantly increased the firing rate of substantia nigra pars compacta neurons from intact rats.

These results strongly suggest that changes in electrophysiological responses observed in substantia nigra pars compacta neurons is caused by degeneration of GABAergic afferents from the substantia nigra pars reticulata following middle cerebral artery occlusion. While previous studies indirectly suggested that hyperexcitation due to deafferentation from the neostriatum may be a major underlying mechanism in delayed degeneration of substantia nigra pars reticulata neurons after middle cerebral artery occlusion, the present electrophysiological experiments provide evidence of hyperexcitation in substantia nigra pars compacta neurons but not in pars reticulata neurons at the chronic phase of striatal infarction.

Section snippets

Surgical preparation

This study was approved by the Animal Research Committee of the Teikyo University School of Medicine and the Kyushu University. The study was carried out using 44 male Sprague–Dawley rats (Shizuoka Lab. Animal Cent., Shizuoka, Japan), aged nine to 12 weeks and weighing 300–420 g. The rats were anaesthetized with 2% halothane, and in 34 rats the proximal portion of the left MCA was exposed by the transretro-orbital approach. In 29 rats the left MCA was then permanently occluded by the

Histopathological changes in substantia nigra neurons after middle cerebral artery occlusion

Histopathologically, acute ischemic changes were limited to the territory supplied by the MCA, which were the lateral part of the neostriatum and the corresponding frontoparietal cortex as described previously.[25]The substantia nigra of the control group did not show any pathological changes. At seven days after MCA occlusion, the SNR became smaller in volume than the control (Fig. 1B). The SNR showed a more marked atrophy after 14 days (Fig. 1C). Neuronal necrosis and gliosis were observed at

No significant alteration of electrophysiological profiles of substantia nigra pars reticulata neurons after middle cerebral artery occlusion

On the basis of our hypothesis that delayed degeneration of SNR neurons after MCA occlusion results from excessive excitation due to loss of inhibitory GABAergic inputs,[27]we expected marked changes in electrophysiological profiles of SNR neurons after MCA occlusion. In the present experiments, however, neither the electrical membrane properties nor synaptic responses of SNR neurons was changed significantly from fifth through sixteenth day after MCA occlusion. We have previously suggested

Conclusions

Histological examination revealed marked atrophy and neurodegeneration in the SNR, whereas the present in vitro electrophysiological study provides no evidence of hyperexcitation in SNR neurons at one to two weeks after MCA occlusion. On the other hand, SNC neurons showed hyperexcitation evidenced by the significant increase in the spontaneous firing rate and the amplitude of EPSPs evoked by STH stimulation at 13–16 days after MCA occlusion. Furthermore, the input resistance of SNC neurons was

Acknowledgements

This study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan. We gratefully acknowledge the excellent technical assistance of Mrs Noriko Kishino.

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Electrophysiological studies of rat substantia nigra neurons in an in vitro slice preparation after middle cerebral artery occlusion

Abstract

Section snippets

Surgical preparation

Histopathological changes in substantia nigra neurons after middle cerebral artery occlusion

No significant alteration of electrophysiological profiles of substantia nigra pars reticulata neurons after middle cerebral artery occlusion

Conclusions

Acknowledgements

Brain Res.

Brain Res.

Brain Res.

Neurosci. Lett.

Brain Res.

Brain Res.

Brain Res.

Brain Res.

Brain Res.

Neurosci. Lett.

Brain Res.

Brain Res.

Neurobiol. Dis.

Neuroscience

Brain Res.

Electrophysiological changes in substantia nigra after striatal infarction

NeuroReport

Reaction of the substantia nigra to massive basal ganglia infarction

Acta neuropath.