Antidromic identification of dopaminergic and other output neurons of the rat substantia nigra

Abstract

In the present study dopamine (DA)-containing and other output neurons of the substantia nigra (SN) wer identified by antidromic stimulation from postulated target nuclei, the caudate-putamen, the thalamus, the cortex and the pontine reticular formation. To guide electrode placements, the topography of the nigrostriatal projection system was determined by retrograde tracing methods. Spontaneously active cells present in the SN were then classified in two groups according to the shape of their action potentials and their firing rate. Type I cells were located mainly in the pars compacta and could be antidromically-activated (AD-activated) from various locations along the course of the nigrostriatal pathway (caudate-putamen, globus pallidus, MFB) but not from other brain areas (ventromedial thalamus, motor cortex, pontine reticular formation). These neurons had a slow bursting pattern of firing, a very slow conduction velocity (0.58 m/sec), and a wide action potential. Their firing rate was dramatically reduced following the intravenous administration of apomorphine (ID 50: 9.3 microgram/kg), or the iontophoretic application of DA and GABA. Type II cells were located predominantly in the pars reticulata; most of them could be AD-activated from the ventromedial thalamus and the MFB but not from the motor cortex. A few of these cells could be AD-activated from the pontine reticular formation and the thalamus. A minority of type II cells, located in or near the pars compacta could be AD-activated from the caudate-putamen. In addition, their conduction velocuty was much higher (2.8 m/sec) and their firing rate far in excess of that exhibited by type I neurons. These neurons were inhibited by the iontophoretic application of GABA but not of DA. The microinjection of 6-hydroxydopamine (a neurotoxin relatively specific against catecholamine-containing neurons) in the vicinity of the MFB blocked selectively the propagation of antidromic spikes in type I but not type II cells. It is concluded that type I cells are the DA neurons of the nigrostriatal pathway. Type II cells are mainly oupput neurons that project to the ventromedial thalamus, the pons and the forebrain. This telencephalic projection most likely constitutes a second, non-DA, fast-conducting nigrostriatal pathway.