Activity Of Pars Reticulata Neurons Research Articles

Regular firing of a single output neuron reduces its own inhibition through endocannabinoids in substantia nigra pars reticulata of juvenile mice

Depolarization-induced suppression of inhibition in substantia nigra pars reticulata suggests that burst-like activity but not regular firing suffices to activate presynaptic endocannabinoid CB1 receptors. To more closely determine the type of activity required, we applied gramicidin perforated patch recording under visual control to substantia nigra slices of juvenile mice. We found that evoked inhibitory postsynaptic currents (eIPSCs) were reduced in amplitude by the spontaneous firing of a neuron under study, whereas silencing this neuron enhanced inhibitory responses. Autonomous firing reduced eIPSCs to 78%±2% in a time- but not frequency-dependent manner. The phenomenon which we termed firing-induced suppression of inhibition was cannabinoid receptor subtype 1–dependent, whereas adenosine A1 receptors played only a minor role. Depletion of intracellular Ca2+ stores abolished the firing-induced suppression of inhibition suggesting that Ca2+ release from internal stores is necessary for the production of endocannabinoids during autonomous firing. We suggest that the Ca2+ influx during autonomous activity of pars reticulata neurons suffices to selectively dampen incoming inhibition from striatal neurons because it is amplified by ryanodine receptor-mediated Ca2+ release from intracellular stores.

Different mechanisms for dopaminergic excitation induced by opiates and cannabinoids in the rat midbrain

1. 1. The mechanism underlying morphine and cannabinoid-induced excitation of meso-accumbens and nigro-striatal dopaminergic neurons was investigated by extracellular single unit recording techniques coupled with antidromic activation from the nucleus accumbens and striatum respectively, in unanesthetized rats. 2. 2. The intravenous administration of cumulative doses (1–4 mg/kg) of morphine, dose-dependently increased the firing rate of dopaminergic neurons projecting to the nucleus accumbens and neostriatum, while the same doses inhibited the activity of pars reticulata neurons of the substantia nigra. Both effects were antagonized by naloxone (0.1 mg/kg i.v.) but not by the selective CB1 receptor antagonist SR 141716A (1 mg/kg i.v.). 3. 3. The intravenous administration of cumulative doses (0.125–0.5 mg/kg) of Δ 9-tetrahydrocannabinol ( Δ 9-THC) also increased the firing rate of meso-accumbens and nigro-striatal dopaminergic neurons; this effect was antagonized by SR 141716A (1 mg/kg i.V.), but not by naloxone. 4. 4. Furthermore, nor Δ 9-THC up to a dose of 1 mg/kg, maximally effective in stimulating dopamine neurons, neither SR 141716A (1 mg/kg i.v.) at a dose able to reverse the stimulatory effect of Δ 9-THC on dopamine cells, did alter the activity of SNr neurons. 5. 5. The results indicate that morphine and Δ 9-THC activate dopaminergic neurons through distinct receptor-mediated mechanisms; morphine may act by removing the inhibitory input from substantia nigra pars reticulata neurons (an effect mediated by μ-opioid receptors). Alternatively, the Δ 9-THC-induced excitation of dopaminergic neurons seems to be mediated by CB1 cannabinoid receptors, while neither μ-opioid receptors nor substantia nigra pars reticulata neurons are involved.

Activity of pars reticulata neurons of monkey substantia nigra in relation to motor, sensory, and complex events.

The behavioral involvement of neurons in the pars reticulata of the substantia nigra (SNpr) in sensory and motor processes was investigated in order to contribute to the understanding of behavior-related neuronal mechanisms in the basal ganglia, of which the SNpr is a major output station. Electrophysiological properties of SNpr neurons were studied with extracellular recordings from single neurons in monkeys performing in a behavioral GO/NO-GO paradigm, employing significant auditory and visual stimuli, forelimb reaching movements, and mouth movements. Neurons in the SNpr discharged impulses of 0.6 to 1.0 ms in duration, at rates of 23 to 145/s (median 68/s). They contrasted with dopaminergic pars compacta neurons of substantia nigra, which discharged longer impulses at rates below 8/s. Two-thirds of more than 100 quantitatively and statistically evaluated SNpr neurons showed changes with temporal relationships to at least one of the events of the behavioral task. One-fifth of all neurons covaried with more than one event. The largest group of task-related neurons increased or decreased activity with contralateral forelimb movements (46% of all neurons). Most of them covaried with large forward reaching of the arm, and only the minority covaried with distal forearm manipulation. None of the SNpr neurons resembled in their changes the timing of activity of single muscles. Many neurons also showed changes with ipsilateral movements, in a similar fashion as on the contralateral side. Changes began rarely before and mostly with or after onset of muscle activity in prime movers. Changes were quantitatively moderate, rarely exceeding a doubling of discharge rate with increases and reductions by 50% with decreases. Movement relations did not appear to be due to somatosensory input. Some neurons increased or decreased their activity in relation to mouth movements (16% of all neurons). Changes were quantitatively moderate as in the case of movement relationships. Nine percent of all neurons decreased their activity after an acoustic preparatory signal and 9% after a light stimulus indicating the GO or NO-GO situation. Latencies were 50-150 ms (median 90 ms) for the auditory and 80-200 ms (median 120 ms) for the visual responses. Twelve percent of all neurons increased or decreased their activity during the waiting and preparation period, which lay between an initial sensory signal and the permission to move for reward.(ABSTRACT TRUNCATED AT 400 WORDS)

Endogenous dopamine can modulate inhibition of substantia nigra pars reticulata neurons elicited by GABA iontophoresis or striatal stimulation

Previous reports from this laboratory have described an ability of iontophoretically applied dopamine to attenuate the inhibitory effects of iontophoresed GABA on neurons of the substantia nigra pars reticulata. This finding raised the question of whether endogenous dopamine, released from dendrites of neighboring pars compacta dopamine neurons, might act as a neuromodulator which diminishes the inhibition of pars reticulata neurons evoked by either GABA iontophoresis or electrical stimulation of the striatonigral GABAergic pathway. Extracellular, single-unit activity of pars reticulata neurons was recorded in male rats anesthetized with chloral hydrate. In one set of studies, d-amphetamine, a drug reported to release dopamine from nigral dendrites, was administered intravenously (1.6 mg/kg) during regular, intermittent iontophoretic pulses of GABA. As had been previously observed with iontophoresed dopamine, i.v. amphetamine significantly lessened the inhibition of reticulata neurons produced by GABA application. This change was reflected by a decrease in GABA's inhibitory potency by 22% relative to the control level of inhibition achieved prior to amphetamine administration. Amphetamine caused no decreases in GABA's effectiveness, however, in animals that had previously received treatments that depleted or destroyed nigral dopamine stores, i.e., in rats pretreated with reserpine and alpha-methyl-p-tyrosine, or in rats with 6-hydroxydopamine lesions of the nigrostriatal dopamine pathway. In a second set of experiments, amphetamine or dopamine was delivered iontophoretically while monitoring the GABA-mediated (bicuculline-reversible) inhibition of reticulata neurons that can be elicited by striatal stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)