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Mechanisms of excitation and inhibition in the nigrostriatal system Richardson, Thomas L.


The extracellular responses of neurons in the corpus striatum following single pulse stimulation of the substantia nigra or dorsal raphe nucleus were investigated in urethane anaesthetized rats, nigral stimulation at low intensities (10 v) evoked single large amplitude spikes while higher intensities (10 to 20 v) evoked, in addition, a high frequency burst of small amplitude spikes or waves. Spontaneous large spikes, or those induced by the administration of glutamate, were inhibited by nigral stimulation. The onset of inhibition coincided with the onset of the burst. If the burst was prevented, inhibition no longer occurred. Neither the inhibitory nor the burst response evoked by nigral stimulation was influenced by iontophoretically or systemically administered antagonists of dopamine or by chemical lesions of the dopaminergic neurons of the nigrostriatal pathway. However the excitation of large units by nigral stimulation was reversibly blocked by dopamine antagonists. Stimulation of the dorsal raphe nucleus produced inhibition of spontaneously active striatal neurons. No excitatory response was ever observed. HEP injected into the striatum was transported to cells in the dorsal raphe nucleus and injection of tritiated leucine into the dorsal raphe nucleus produced significant transport of radio labelled protein to the caudate nucleus. It is concluded that the burst response is produced by excitation of striatal interneurons through collaterals of the striatonigral pathway which are intrinsic to the nucleus. Nigral stimulation causes an antidromic activation of the axon and a subsequent orthodromic activation of its collaterals. The interneurons activated by this "axon reflex" are inhibitory in function. It is further concluded that the dopaminergic neurons of the nigrostriatal tract make excitatory synaptic contact with striatal neurons in the central region of the nucleus. At least some of these target neurons project, in turn, to the globus pallidus.

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