Electrophysiology of dopaminergic and non‐dopaminergic neurones of the guinea‐pig substantia nigra pars compacta in vitro.

Abstract

SUMMARY1. The membrane properties of substantia nigra pars compacta neurones were studied using an in vitro slice preparation of guinea-pig midbrain.2. Neurones were divided into two classes based on their electrophysiological properties: bursting neurones displayed a burst of several rapidly accommodating action potentials in response to relaxation of hyperpolarizing current injected through the microelectrode, while non-bursting neurones produced regularly spaced action potentials. These neuronal types were found to be electrophysiologically distinct from those recorded in the substantia nigra pars reticulata and the subthalamic nucleus.3. Non-bursting neurones, which comprised ca 85% of the sampled cells, were characterized by a slow, pacemaker pattern of firing at rest, broad action potentials, a pronounced spike after-hyperpolarization, long membrane time constants, and strong transient outward and time-dependent inward rectification.4. Bursting neurones, comprising ca 15% of the sample, displayed rapid firing rates at rest, fast action potentials, a shallow spike after-hyperpolarization and briefer membrane time constants. All of these parameters were significantly different from those of the non-bursting type. Bursting neurones lacked transient outward or time-dependent inward rectification.5. Both types of cells were capable of generating pronounced calcium-dependent, low-threshold spikes in the presence of tetrodotoxin (TTX). However, only the nonbursting type displayed calcium-dependent rhythmic oscillations in membrane potential near resting potential in the presence of TTX. The firing rate, action potential shape and after-hyperpolarization of non-bursting neurones were strongly influenced by calcium-dependent currents.6. The majority of cells were injected with biocytin, which allowed morphological reconstruction of the neurones and confirmation of their location within the pars compacta. Non-bursting neurones had variable soma shapes and their dendrites were mostly directed in a medio-lateral direction. Many cells extended some of their dendrites into the pars reticulata. Bursting neurones were mainly fusiform in shape with their dendrites oriented in a medio-lateral direction; a few had dendrites extending into the pars reticulata. 7. Thirty-six neurones were also double labelled using a combination of biocytin Non-bursting neurones all displayed TH immunofluorescence, while none of the bursting neurones were TH positive. 8. Bursting neurones were found predominantly in the dorsal part of the rostral pars compacta, while non-bursting cells were found throughout. The distribution of bursting neurones paralleled the distribution of glutamic acid decarboxylase (GAD)-immunoreactive neurones in the pars compacta.9. These results strongly suggest that non-bursting cells are dopaminergic, while bursting cells are non-dopaminergic, and probably GABAergic. Possible functional correlates of these cell types are discussed.

Regulation of a potassium conductance in rat midbrain dopamine neurons by intracellular adenosine triphosphate (ATP) and the sulfonylureas tolbutamide and glibenclamide

“…2A). All these properties correspond to those of dopaminecontaining SN neurons demonstrated in previous studies (Grace and Onn, 1989;Yung et al, 1991), and to those of cells presumed to be dopamine-containing in other studies (such as Lacey et al, 1989;Riiper et al, 1990~;Johnson and North, 1992;see Lacey, 1993, for review). Thus, the cells studied here are considered to be dopamine neurons.…”

Dopamine neurons change the type of excitability in response to stimuli

“…The subthreshold Ca 2+ -K + oscillatory mechanism underlies the generation of low frequency background firing in a significant subpopulation of DA neurons [7][8][9][10][11][12][13][14][15][16][17][18]51]. However, a number of studies suggest a contribution of Ca 2+ -independent currents to oscillations [26,19,25,27,46].…”

“…The type of excitability is determined by the internal properties of the currents contributing to pacemaking in the DA neuron. L-type Ca 2+ and SK-type Ca 2+ -dependent K + currents are the core currents that traditionally constitute this mechanism [7][8][9][10][11][12][13][14][15][16][17][18] (but see the section on the mechanisms of DA neuron pacemaking). However, our model shows that the mechanism results in type II excitability, in which a hyperpolarizing current blocks the voltage oscillations without restoring a low frequency.…”

“…The current composition producing low-frequency pacemaking in DA neurons is of vibrant debate among researchers in the field. A number of experimental [7][8][9][10][11][12][13][14][15][16][17][18][19] studies suggests that the maintenance of tonic firing in at least a subpopulation of DA neurons relies on the interactions of the voltage gated calcium (Ca 2+ ) and SK-type Ca 2+ -dependent potassium (K + ) currents Slow pacemaking in our model relies on a subthreshold Ca 2+ -K + oscillatory mechanism, similar to a number of well-established models [4,[20][21][22][23][24]. Interaction between Ca 2+ and Ca 2+ -dependent K + currents periodically brings the neuron to the spike threshold and generates a metronomic firing pattern.…”

Pallidal control of substantia nigra dopaminergic neuron firing pattern and its relation to extracellular neostriatal dopamine levels

“…These neurons are spontaneously active with a mean firing rate around 30 Hz in anesthetized rats (Celada et al, 1999) and have axonal conduction velocities similar to pallidal neurons, around 3-4 m/s (Deniau et al, 1978;Guyenet and Aghajanian, 1978). 191 At one time it was believed that the nondopaminergic nigral neurons that were the source of the GABAergic input to the dopaminergic neurons were true local circuit neurons, leading them to be explicitly referred to as ''interneurons'' in the literature (e.g., Bunney, 1979, 1985;Mereu and Gessa, 1985;Araneda and Bustos, 1989;Yung et al, 1991;Zhang et al, 1993;Bontempi and Sharp, 1997). However, the neuroanatomical and electrophysiological properties reported for the putative pars reticulata GABAergic interneurons are not very different from those of antidromically identified nigrothalamic and nigrotectal projection neurons (Matsuda et al, 1987;Yung et al, 1991;Lee and Tepper, 2007 but see also Grace and Bunney, 1979;Grace et al, 1980) that have been shown to send axon collaterals to the pars compacta which synapse onto dopaminergic neurons Grofova et al, 1982;Hajos and Greenfield, 1993;Tepper et al, 1995Tepper et al, , 2002Mailly et al, 2003).…”