Inhibitory synaptic potentials in guinea‐pig substantia nigra dopamine neurones in vitro.

Abstract

1. The properties of stimulus-evoked and spontaneous inhibitory synaptic potentials were examined in guinea-pig substantia nigra dopamine neurones in sagittal and coronal midbrain slices in the presence of glutamate receptor antagonists. 2. Focal electrical stimulation within the substantia nigra, cerebral peduncle, internal capsule or the striatum evoked a biphasic IPSP consisting of a fast and a slow component, with peak latencies of about 30 and 250 ms, respectively. The fast component was sensitive to chloride injection, reversed polarity at -79.4 +/- 1.1 mV and was blocked by the GABAA receptor antagonists picrotoxin and bicuculline. The slow IPSP reversed at -99.3 +/- 5.4 mV and was blocked by the GABAB receptor antagonists 2-hydroxysaclofen and CGP 35348. 3. Spontaneous IPSPs were observed in many neurones. These events reversed polarity at -77.5 +/- 2.6 mV and were completely blocked by bicuculline and/or picrotoxin. In the presence of TTX, small spontaneous events remained which probably represent miniature IPSPs. In coronal slices, application of 4-aminopyridine raised the frequency of spontaneous IPSPs, presumably by activating nigral interneurones, but failed to reveal spontaneous biphasic IPSPs or spontaneous pure slow IPSPs. 4. The amplitude of the fast IPSPs fluctuated from trial to trial. Amplitude histograms of minimal fast IPSPs displayed evenly spaced peaks, suggesting that synaptic transmission is quantal at these synapses. The measured peak spacing depended on the driving force for Cl-. 5. The fast IPSP showed little or no paired-pulse depression, and in the presence of 2-hydroxysaclofen (400-600 microM) showed paired-pulse facilitation. The GABAB agonist baclofen inhibited the fast IPSP via a presynaptic mechanism. The pharmacologically isolated slow IPSP showed marked paired-pulse facilitation. 6. It is concluded that synaptic inhibition in the substantia nigra is mediated by GABA, is relatively resistant to frequency-dependent depression and is regulated by presynaptic GABAB autoreceptors. Striatonigral and pallidonigral fibres activate both GABAA and GABAB receptors, while intranigral pathways appear to activate predominantly GABAA receptors.

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

“…In contrast to the in vivo results, local stimulation of substantia nigra in vitro leads to both short latency and long latency (onset about 35 ms, time to peak around 150 ms; Hausser and Yung, 1994) IPSPs. The short latency IPSPs are blocked by bicuculline and picrotoxin whereas the long latency IPSPs are blocked by the selective GABA B receptor antagonists, CGP 35348 or 2-hydroxysaclofen, thereby identifying them as GABA A and GABA B IPSPs, respectively (Saitoh et al, 2004).…”

“…2. This unmasking effect is likely due to blockade of presynaptic GABA B receptors present on GABAergic afferents to substantia nigra (Giralt et al, 1990;Hausser and Yung, 1994;Shen and Johnson, 1997;Paladini et al, 1999a;Boyes and Bolam, 2003, see Misgeld, this volume), a property shared by the striatal, pallidal, and pars reticulata afferents (Paladini et al, 1999a but see Cameron and Williams, 1993). Thus, in vivo, most or all of the postsynaptic effects of striatal, pallidal, and pars reticulata GABAergic inputs in vivo appear to be mediated by GABA A receptors, with the GABA B receptors acting predominantly as presynaptic inhibitory autoreceptors.…”

“…The short latency IPSPs are blocked by bicuculline and picrotoxin whereas the long latency IPSPs are blocked by the selective GABA B receptor antagonists, CGP 35348 or 2-hydroxysaclofen, thereby identifying them as GABA A and GABA B IPSPs, respectively (Saitoh et al, 2004). Although GABA B IPSPs can sometimes be elicited by single pulse stimuli, they are usually not seen in response to minimal stimuli that evoke GABA A IPSPs (Hausser and Yung, 1994) and are most often reported to follow trains of stimuli at higher intensities Cameron and Williams, 1993;Greenfield, 1993, 1994;Saitoh et al, 2004). Although spontaneous GABAergic IPSPs are frequently reported in dopaminergic neurons in vitro (e.g., Hausser and Yung, 1994), these appear to be strictly GABA A -mediated.…”

“…Although GABA B IPSPs can sometimes be elicited by single pulse stimuli, they are usually not seen in response to minimal stimuli that evoke GABA A IPSPs (Hausser and Yung, 1994) and are most often reported to follow trains of stimuli at higher intensities Cameron and Williams, 1993;Greenfield, 1993, 1994;Saitoh et al, 2004). Although spontaneous GABAergic IPSPs are frequently reported in dopaminergic neurons in vitro (e.g., Hausser and Yung, 1994), these appear to be strictly GABA A -mediated. It was originally suggested that striatal-evoked GABAergic inhibition of dopaminergic neurons but not that arising from globus pallidus or substantia nigra pars reticulata, was mediated by GABA B receptors (Cameron and Williams, 1993).…”

Possible Contribution of the Basal Ganglia Brainstem System to the Pathogenesis of Parkinson’s Disease

“…Because loss of cholinergic PPN neurons were observed not only in PSP (75-80%) but also PD (43-57%) (Hirsch et al, 1987;Jellinger, 1988;Zweig et al, 1987Zweig et al, , 1989, the loss of cholinergic PPN neurons in both diseases could attribute to attentive and cognitive impairments and sleep deficiencies in these diseases (Scarnati & Florio, 1997). Both neuroanatomical (von Krosigk et al, 1992;Smith & Bolam, 1990) and electrophysiological (Häusser & Yung, 1994;Saitoh et al, 2004;Paladini et al, 1999) studies demonstrated that dopaminergic neurons, as well as cholinergic neurons, receive GABAergic inhibitory effects from the basal ganglia, particularly from the SNr. Consequently a BG-BS system appears to involve the interdigitation of motor information with information relating to reward and reinforcement by modulating the excitability of both dopaminergic and cholinergic systems.…”