title: Topographic heterogeneity of substantia nigra neurons: diversity in intrinsic membrane properties and synaptic inputs.
abstract: The passive and active membrane properties of substantia nigra neurons were recorded in vitro at various locations throughout its anterior-posterior extent and their responses to extracellular electrical stimulation within the pars reticulata were analysed. One class of nigral pars compacta cell showed the well-established electrophysiological characteristics of mesencephalic dopaminergic neurons, i.e. spontaneous discharge in a very rhythmic, pacemaker fashion without bursting activity and with broad action potentials. However, these neurons could be subdivided further according to differences in electrophysiological properties which correlated with their position within the substantia nigra. Thus, neurons recorded from the anterior part of the substantia nigra, at the level of the mammilary bodies displayed a significantly higher firing rate and shorter action potential than those located in posterior slices at the level of the accessory optic tract. The location of the cell was also a critical factor in its response to stimulation of the pars reticulata: in anterior slices only 45.5% of the cells responded with inhibitory postsynaptic potentials to stimulation, while in posterior slices inhibitory postsynaptic potentials occurred in 85.7% of the neurons (n = 44). In addition, anteriorly located neurons were more sensitive to direct electrical stimulation than posteriorly located cells and they also exhibited excitatory postsynaptic potentials (33%) on pars reticulata stimulation. However, the actual properties of inhibitory postsynaptic potentials were essentially the same in these neurons irrespective of whether they were located either in the anterior or posterior part of the nigra: reversal potentials of inhibitory postsynaptic potentials were found at two distinct potentials indicating involvement of both GABAA and GABAB receptors. This deduction is also supported by additional pharmacological findings: application of the GABAA antagonist, bicuculline methiodide and/or GABAB antagonist, 2-hydroxysaclofen blocked both the inhibitory postsynaptic potentials and the cessation of spontaneous firing activity of the cells to stimulation of the pars reticulata. The other type of pars compacta neuron recorded discharges phasically and was located exclusively in the anterior pole of the substantia nigra. These cells showed a wide range of spontaneous firing activity, a non-rhythmic, irregular pattern of firing, a shorter action potential width and the presence of a low-threshold calcium conductance. These "phasic" neurons also differed greatly from other compacta neurons in their response to pars reticulata stimulation: spontaneous activity of these cells was not inhibited nor did they show inhibitory postsynaptic potentials. Instead, the majority was preferentially activated by direct stimulation of the dendrites, although excitatory postsynaptic potentials could also be evoked.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: University Department of Pharmacology, Oxford, U.K.
authors.forename: M
authors.initials: M
authors.lastname: Hajós
authors.forename: S A
authors.initials: SA
authors.lastname: Greenfield
mesh_terms: D000200:Action Potentials; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D015415:Biomarkers; D002462:Cell Membrane / Q000502:physiology*; D003712:Dendrites / Q000648:ultrastructure; D004298:Dopamine / Q000378:metabolism; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000032:analysis; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D013378:Substantia Nigra / Q000166:cytology* / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
chemical_list: D015415:Biomarkers; D009419:Nerve Tissue Proteins; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D001640:Bicuculline