Stimulation Of Substantia Nigra Research Articles

Current Steering Using Multiple Independent Current Control Deep Brain Stimulation Technology Results in Distinct Neurophysiological Responses in Parkinson's Disease Patients.

BackgroundDeep brain stimulation (DBS) is an effective neuromodulation therapy to treat people with medication-refractory Parkinson’s disease (PD). However, the neural networks affected by DBS are not yet fully understood. Recent studies show that stimulating on different DBS-contacts using a single current source results in distinct EEG-based evoked potentials (EPs), with a peak at 3 ms (P3) associated with dorsolateral subthalamic nucleus stimulation and a peak at 10 ms associated with substantia nigra stimulation. Multiple independent current control (MICC) technology allows the center of the electric field to be moved in between two adjacent DBS-contacts, offering a potential advantage in spatial precision.ObjectiveDetermine if MICC precision targeting results in distinct neurophysiological responses recorded via EEG.Materials and MethodsWe recorded cortical EPs in five hemispheres (four PD patients) using EEG whilst employing MICC to move the electric field from the most dorsal DBS-contact to the most ventral in 15 incremental steps.ResultsThe center of the electric field location had a significant effect on both the P3 and P10 amplitude in all hemispheres where a peak was detected (P3, detected in 4 of 5 hemispheres, p < 0.0001; P10, detected in 5 of 5 hemispheres, p < 0.0001). Post hoc analysis indicated furthermore that MICC technology can significantly refine the resolution of steering.ConclusionUsing MICC to incrementally move the center of the electric field to locations between adjacent DBS-contacts resulted in significantly different neurophysiological responses that may allow further precision of the programming of individual patients.

Combined Stimulation of the Substantia Nigra and the Subthalamic Nucleus for the Treatment of Refractory Gait Disturbances in Parkinson's Disease: A Preliminary Study.

Deep brain stimulation of the subthalamic nucleus is efficient for the treatment of motor symptoms (i.e., tremors) in patients with Parkinson’s disease. Gait disorders usually appear during advanced stages of idiopathic Parkinson’s disease in up to 80% of patients and have an important impact on their quality of life. The effects of deep brain stimulation of the subthalamic nucleus on gait and balance are still controversial. For this reason, alternative targets have been considered, such as stimulation of the pedunculopontine nucleus and the pars reticulata of substantia nigra, involved in the integration of the functional connections for gait. Due to the proximity of the subthalamic nucleus to the substantia nigra, their combined stimulation is feasible and may lead to better outcomes, improving axial symptoms. Our objective was to prospectively compare simultaneous stimulation of both structures versus conventional subthalamic stimulation in improving gait disorders. In ten patients with advanced Parkinson’s disease, deep brain stimulation leads (eight linear contacts) were implanted, and gait analysis was performed 6 months after surgery in off-stimulation and after 4 weeks of dual or single subthalamic stimulation. An improvement in gait parameters was confirmed with both stimulation conditions, with better results with combined substantia nigra and subthalamic stimulation compared with conventional subthalamic stimulation. Further studies are needed to determine if this effect remains after long-term dual-target stimulation.

Dopaminergic- and cholinergic-inputs from substantia nigra and pedunculo-pontine tegmentum, respectively, converge in amygdala to modulate rapid eye movement sleep in rats

Dreams appear intermittently during phasic rapid eye movement sleep (REMS). Although reasonable progress has been made about neuro-physio-pharmacological mechanism of appearance of REMS, appearance of dreams is a mystery. Isolated studies have reported that substantia nigra (SN) withdraws inhibition from pedunculo-pontine tegmentum (PPT) acetylcholine (ACh)-ergic REM-ON neurons to trigger REMS; some REM-ON neurons become phasically active during REMS; amygdala (Amyg), a limbic structure associated with emotions, may be related with dreaming like state; Amyg receives projections from both SN-Dopamine (DA)-ergic and PPT-ACh-ergic neurons. Collating these isolated findings, we proposed that on the background of REMS, SN-DA-ergic and PPT-ACh-ergic inputs phasically activate Amyg-neurons to manifest dreams. In the absence of better criteria, we recorded electrophysiological characteristics of REMS as the closest objective read-out for dreams in surgically prepared, chronic, freely moving rats. Microinjection of either DA-ergic or ACh-ergic agonist [Quinpirole (Qnp) or Carbachol (Carb)] bilaterally into Amyg increased, while antagonists [Haloperidol (Hal) or Scopolamine (Scop)] reduced REMS. Electrical stimulation of either bilateral SN or PPT increased REMS, which however, was prevented when stimulated in presence of Hal or Scop, respectively into the Amyg. These findings confirm and support our contention that SN-DA-ergic and PPT-ACh-ergic inputs integrate in Amyg for REMS regulation. Further, subject to confirmation in humans, we propose that on the background of REMS, some phasic PPT-ACh-ergic-REM-ON neurons intermittently trigger some neurons in Amyg, the area known to be associated with memory and emotions, causing intermittent appearance of REMS-associated dreams and in REMS behavior disorder.

Anticipatory postural adjustments are modulated by substantia nigra stimulation in people with Parkinson's disease and freezing of gait

BackgroundA precise understanding of the neuronal circuits involved in the control of anticipatory postural adjustments (APAs) for gait initiation is missing. Neurostimulation in Parkinson's disease (PD) provides a method of modulating APAs to gain insight into the underlying circuitry. ObjectiveOur objective was to investigate if APA kinematics for step initiation could be modulated by high frequency stimulation of the subthalamic nucleus (STN) or substantia nigra pars reticulata (SNr) in people with PD and freezing of gait (FoG). MethodsWe studied 14 people with PD and FoG using neurostimulation of the STN and SNr areas after overnight withdrawal of dopaminergic medication on the instrumented stand and walk test. We tested patients in the following randomized conditions: ‘off stimulation’, ‘STN’ stimulation (only), and ‘SNr’ stimulation (only). Patients were blinded to the stimulation condition. The APAs were recorded with inertial sensors and processed offline. Moreover, we assessed clinical scores with respect to motor symptoms, non-motor symptoms, executive function, and FoG. ResultsSNr but not STN stimulation modulated the anterio-posterior size of APA. The SNr modulation of APA was associated with the stimulation effect on FoG (trend; r = 0.580, P = 0.102). The APA modulation was not correlated with any other cognitive or clinical measures. ConclusionNeuromodulation of the SNr but not of the STN modulated APAs in PD patients with FoG. The different effects of STN or SNr on the kinematic parameters of APA support the concept of segregate targets in order to address diverse kinematic components of PD gait.

Impact of Combined Subthalamic Nucleus and Substantia Nigra Stimulation on Neuropsychiatric Symptoms in Parkinson's Disease Patients.

The goal of the study was to compare the tolerability and the effects of conventional subthalamic nucleus (STN) and combined subthalamic nucleus and substantia nigra (STN+SNr) high-frequency stimulation in regard to neuropsychiatric symptoms in Parkinson's disease patients. In this single center, randomized, double-blind, cross-over clinical trial, twelve patients with advanced Parkinson's disease (1 female; age: 61.3 ± 7.3 years; disease duration: 12.3 ± 5.4 years; Hoehn and Yahr stage: 2.2 ± 0.39) were included. Apathy, fatigue, depression, and impulse control disorder were assessed using a comprehensive set of standardized rating scales and questionnaires such as the Lille Apathy Rating Scale (LARS), Modified Fatigue Impact Scale (MFIS), Becks Depression Inventory (BDI-I), Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale (QUIP-RS), and Parkinson's Disease Questionnaire (PDQ-39). Three patients that were initially assigned to the STN+SNr stimulation mode withdrew from the study within the first week due to discomfort. Statistical comparison of data retrieved from patients who completed the study revealed no significant differences between both stimulation conditions in terms of mean scores of scales measuring apathy, fatigue, depression, impulse control disorder, and quality of life. Individual cases showed an improvement of apathy under combined STN+SNr stimulation. In general, combined STN+SNr stimulation seems to be safe in terms of neuropsychiatric side effects, although careful patient selection and monitoring in the short-term period after changing stimulation settings are recommended.

Activity of hippocampal neurons upon high frequency stimulation of substantia nigra in experimentally induced Parkinson's disease in rats.

Activity of hippocampal neurons upon high frequency stimulation of substantia nigra in experimentally induced Parkinson's disease in rats.

Modulation of Synaptic Processes in Cortical Neurons in Response to Painful Stimulation and Analgesia

We studied effects of electrical stimulation of the substantia nigra (SN), locus coeruleus (LC), raphe nuclei (RN), substantia innominata (SIn), nucleus caudatus (NC) and central grey (CG) on postsynaptic processes evoked in neurons of the cat somatosensory cortex by excitation of nociceptive and non-nociceptive afferent inputs (intense stimulation of the dental pulp and moderate stimulation of the thalamic ventroposteromedial nucleus, VPMN, respectively). We analyzed intracellularly recorded activity of cortical cells activated exclusively by stimulation of nociceptors and cells activated by both nociceptive and non-nociceptive influences (“nociceptive” and convergent neurons). In neurons of both groups, stimulation of both nociceptive afferents and thalamic VPMN resulted in the development of successions of EPSP – action potential (AP) or their series – IPSP (IPSP duration 200–300 msec). Conditioning electrical stimulation the above-mentioned nuclei induced suppression of synaptic reactions that occur in cortical neurons in response to stimulation of nociceptive inputs. The maximum of inhibition was observed at test intervals of 600 to 800 msec. We observed certain parallelism between conditioning influentions of PAG activation and effects of systemic injections of morphine. Decrease in the amplitude or complete postsynaptic inhibition of IPSP in cortical neurons under different treatments associate with the occurrence of convulsive epileptic activity, and at the painful action with analgesic effect. Discussed are the mechanisms for modulatory influences exerted by conditioning stimulation of SN, LC, RN, NC, SIn and CG on the somatosensory neurons, activated upon excitation of high-threshold (nociceptive) afferent inputs.

Roles for nigrostriatal—not just mesocorticolimbic—dopamine in reward and addiction

Forebrain dopamine circuitry has traditionally been studied by two largely independent specialist groups: students of Parkinson's disease who study the nigrostriatal dopamine system that originates in the substantia nigra (SN), and students of motivation and addiction who study the role of the mesolimbic and mesocortical dopamine systems that originate in the ventral tegmental area (VTA). The anatomical evidence for independent nigrostriatal and mesolimbic dopamine systems has, however, long been obsolete. There is now compelling evidence that both nominal "systems" participate in reward function and addiction. Electrical stimulation of both SN and VTA is rewarding, blockade of glutamatergic or cholinergic input to either SN or VTA attenuates the habit-forming effects of intravenous cocaine, and dopamine in both nigrostriatal and mesocorticolimbic terminal fields participates in the defining property of rewarding events: the reinforcement of memory consolidation. Thus, the similarities between nigrostriatal and mesolimbic dopamine systems can be as important as their differences.

Influence of Electrical Stimulation of Substantia Nigra on the Neuronal Activity of Central Gray Matter during Tail Flick Reflex

Event Abstract Back to Event Influence of Electrical Stimulation of Substantia Nigra on the Neuronal Activity of Central Gray Matter during Tail Flick Reflex Elene Abzianidze1*, Tinatin Tkemaladze1, Viola Berishvili1, Gulnazi Gurtskaia2 and Merab Tsagareli2 1 Tbilisi State Medical University, Georgia 2 I. Beritashvili Institute of Physiology, Georgia Aim of Investigation: Influence of electrical stimulation of substantia nigra on the neuronal activity of Central Gray Matter during tail flick reflex was investigating in albino rats. Methods: As a model of pain we used tail stimulation with focused infrared light. An opioid analgesic (morphine, 0.5-4 mg/kg) and an agonist (parlodel, 0.05-0.1 mg/kg) and antagonist (alkopride, 0.1-1.2 mg/kg) of dopaminergic receptors were used for neuropharmacological analysis. Results:In chronic experiments on albino rats it was shown that electrical stimulation of substantia nigra induces activation of the “off”neurons and inhibition of “on” neurons of the Central Gray Matter (CGM); the latency of the tail-flick reflex was increased as well. After injection of alkopride, the antagonist of dopaminergic receptor, the antinocicptive effect induced by stimulation of substantia nigra decreased. Injection of parlodel (0.05-1 mg/kg), as well as morphine (2-4 mg/kg) increases latent period of nociceptive reflex dose-dependently. Subthreshold electrical stimulation of substantia nigra against a background of subanalgetic dose of morphine (0.5-1 mg/kg) induced potentiation of morphine’s effect. Conclusions:Antinociceptive effect of substantia nigra on nociceptive afferentation accomplished with interaction of opiate and dopaminergic systems. Acknowledgements: This study was supported by: Tbilisi State Medical University & Georgian National Science Foundation (GNSF/ST07/6-234). Conference: 41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009. Presentation Type: Poster Presentation Topic: Poster presentations Citation: Abzianidze E, Tkemaladze T, Berishvili V, Gurtskaia G and Tsagareli M (2009). Influence of Electrical Stimulation of Substantia Nigra on the Neuronal Activity of Central Gray Matter during Tail Flick Reflex. Conference Abstract: 41st European Brain and Behaviour Society Meeting. doi: 10.3389/conf.neuro.08.2009.09.065 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 05 Jun 2009; Published Online: 05 Jun 2009. * Correspondence: Elene Abzianidze, Tbilisi State Medical University, Tbilisi, Georgia, eabzianidze@tsmu.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Elene Abzianidze Tinatin Tkemaladze Viola Berishvili Gulnazi Gurtskaia Merab Tsagareli Google Elene Abzianidze Tinatin Tkemaladze Viola Berishvili Gulnazi Gurtskaia Merab Tsagareli Google Scholar Elene Abzianidze Tinatin Tkemaladze Viola Berishvili Gulnazi Gurtskaia Merab Tsagareli PubMed Elene Abzianidze Tinatin Tkemaladze Viola Berishvili Gulnazi Gurtskaia Merab Tsagareli Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Modulation of Postsynaptic Responses of Nociceptor-Activated Neurons of the Cat Somatosensory Cortex by Stimulation of the Substantia Nigra

We studied the effect of electrical stimulation of the substantia nigra (SN) on postsynaptic processes evoked in neurons of the somatosensory cortex of the cat by stimulation of nociceptive (intense stimulation of the dental pulp) and non-nociceptive (moderate, in strength, stimulations of the n. infraorbitalis and ventroposteromedial nucleus, VPM, of the thalamus) afferent inputs. The intracellularly recorded 7 cells activated exclusively by stimulation of dental nociceptors and 10 cells activated by both nociceptive and non-nociceptive afferent volleys (nociceptive and convergent cortical neurons, respectively) were examined in detail. Complexes EPSP–action potential–long-lasting IPSP (up to 200–300 msec) developed in neurons of both groups after stimulations of both nociceptive afferents and the thalamic VPM. Conditioning stimulation of the SN preceding test stimulation of the dental pulp or VPM with intervals from 100 to 700 msec resulted in selective suppression of IPSPs; their amplitudes decreased by 40–60%. The maximum effect in both cases was observed at conditioning/test intervals of 300 to 700 msec. Under conditions of SN stimulation, the release of dopamine, by affecting receptors and secondary messengers, modulates postsynaptic activity in the cortical GABA-ergic system and decreases the amplitude of IPSPs induced by stimulations of both nociceptors (dental pulp) and low-threshold afferent inputs (VPM of the thalamus). This process can be mediated by both pre-synaptic and post-synaptic mechanisms.

Dopamine D2 receptor-dependent modulation of striatal NO synthase activity

Striatal nitric oxide (NO)-producing interneurons receive synaptic contacts from midbrain dopamine (DA) neurons and are regulated by phasic DA transmission. Classic antipsychotic drugs elevate neuronal NO synthase (NOS) expression in the rat striatum. Given that NO signaling potently modulates the membrane excitability of striatal projection neurons, it is plausible that up-regulation of NOS activity after DA D2 receptor blockade contributes to the therapeutic efficacy and/or motor side effects associated with antipsychotic drugs. This study assessed the impact of DA D(2) receptor activation on striatal NOS activity in vivo. Characterization of the dopaminergic regulation of striatal NO signaling will be relevant for understanding the mechanism(s) of action of antipsychotic drugs. Striatal NO efflux, evoked via electrical stimulation of the substantia nigra (SN) or systemic administration of the DA D(1) receptor agonist SKF 81297, was assessed in anesthetized rats using an NO-selective amperometric microsensor. The facilitatory effect of SN stimulation on striatal NO efflux was attenuated by systemic administration of the DA D(2) receptor agonist quinpirole. Conversely, administration of the DA D(2) receptor antagonist eticlopride augmented evoked NO efflux. NO efflux induced by systemic administration of SKF 81297 was attenuated by quinpirole and restored by co-administration of quinpirole and eticlopride. The facilitatory effect of SKF 81297 on NO efflux was also significantly attenuated after pretreatment with the non-specific NOS inhibitor methylene blue. Activation of NO synthesis by phasic DA transmission is down-regulated via a DA D2 receptor-dependent mechanism. DA D(2) receptor activation opposes DA D(1) receptor activation of NO synthesis at a site postsynaptic to the DA terminal. Further studies examining NO-DA dynamics may have potential to reveal novel therapeutic strategies to treat various brain disorders.

Phasic Dopaminergic Transmission Increases NO Efflux in the Rat Dorsal Striatum via a Neuronal NOS and a Dopamine D1/5 Receptor-Dependent Mechanism

Dysfunctional neurotransmission within striatal networks is believed to underlie the pathophysiology of several neurological and psychiatric disorders. Nitric oxide (NO)-producing interneurons have been shown to play a critical role in modulating striatal synaptic transmission. These interneurons receive synaptic contacts from midbrain dopamine (DA) neurons and may be regulated by DA receptor activation. In the current study, striatal NO efflux was measured in anesthetized male rats using an NO-selective electrochemical microsensor and the role of DA in modulating NO synthase (NOS) activity was assessed during electrical or chemical (bicuculline) stimulation of the substantia nigra (SN). Electrical stimuli were patterned to approximate the natural single spike or burst firing activity of midbrain DA neurons. Electrical stimulation of the SN at low frequencies induced modest increases in striatal NO efflux. In contrast, train stimulation of the SN robustly increased NO efflux in a stimulus intensity-dependent manner. NO efflux evoked by SN stimulation was similar in chloral hydrate- and urethane-anesthetized rats. The facilitatory effect of train stimulation on striatal NO efflux was transient and attenuated by systemic administration of the neuronal NOS inhibitor 7-nitroindazole and the nonselective NOS inhibitor methylene blue. Moreover, the increase in NO efflux observed during chemical and train stimulation of the SN was attenuated following systemic administration of the DA D(1/5) receptor antagonist SCH 23390. SCH 23390 also blocked NO efflux induced by systemic administration of the D(1/5) agonist SKF 81297. These results indicate that neuronal NOS is activated in vivo by nigrostriatal DA cell burst firing via a DA D(1/5)-like receptor-dependent mechanism.

A cellular mechanism of reward-related learning.

Positive reinforcement helps to control the acquisition of learned behaviours. Here we report a cellular mechanism in the brain that may underlie the behavioural effects of positive reinforcement. We used intracranial self-stimulation (ICSS) as a model of reinforcement learning, in which each rat learns to press a lever that applies reinforcing electrical stimulation to its own substantia nigra. The outputs from neurons of the substantia nigra terminate on neurons in the striatum in close proximity to inputs from the cerebral cortex on the same striatal neurons. We measured the effect of substantia nigra stimulation on these inputs from the cortex to striatal neurons and also on how quickly the rats learned to press the lever. We found that stimulation of the substantia nigra (with the optimal parameters for lever-pressing behaviour) induced potentiation of synapses between the cortex and the striatum, which required activation of dopamine receptors. The degree of potentiation within ten minutes of the ICSS trains was correlated with the time taken by the rats to learn ICSS behaviour. We propose that stimulation of the substantia nigra when the lever is pressed induces a similar potentiation of cortical inputs to the striatum, positively reinforcing the learning of the behaviour by the rats.

Inhibition by aripiprazole of dopaminergic inputs to striatal neurons from substantia nigra.

Aripiprazole (OPC-14597) elicits both dopamine D(2) agonist and antagonist activities on dopaminergic neurons of the ventral tegmental area and nucleus accumbens neurons, respectively. However, the electrophysiological action of this drug on the striatal neurons is not clear. Therefore, the present electrophysiological study was performed to determine if aripiprazole modified the striatal neurons as a D(2) receptor agonist or antagonist. Spikes elicited by stimulation of pars compacta of the substantia nigra (SN) were extracellularly recorded from the striatal neurons with a glass microelectrode attached along a seven- barreled micropipette. Each barrel was filled with aripiprazole, quinpirole (D(2) receptor agonist), domperidone (D(2) receptor antagonist), glutamate or 2 M NaCl. The drugs were microiontophoretically applied on the neurons being recorded. The effects of aripiprazole on SN stimulation-induced spikes of striatal neurons that were inhibited by domperidone were examined. Microiontophoretic application of aripiprazole inhibited spikes elicited by SN stimulation in all 18 neurons tested in a dose-dependent manner. In addition, quinpirole-induced firing was inhibited by aripiprazole in all ten neurons tested. However, glutamate-induced spontaneous firing was not affected by aripiprazole in any of the ten neurons tested. These findings suggest that aripiprazole acts as a dopamine D(2) receptor antagonist on striatal neurons receiving excitatory inputs from the SN.

Cardiovascular depressor responses to stimulation of substantia nigra and ventral tegmental area.

Experiments were done in alpha-chloralose-anesthetized, paralyzed, and artificially ventilated rats to investigate the effect of L-glutamate (Glu) stimulation of the substantia nigra (SN) and ventral tegmental area (VTA) on arterial pressure (AP) and heart rate (HR). Glu stimulation of the SN pars compacta (SNC) elicited decreases in both mean AP (MAP; -18.9 +/- 1.3 mmHg; n = 52) and HR (-26.1 +/- 1.6 beats/min; n = 46) at 81% of the sites stimulated. On the other hand, stimulation of the SN pars lateralis or pars reticulata did not elicit cardiovascular responses. Stimulation of the adjacent VTA region elicited similar decreases in MAP (-18.0 +/- 2.6 mmHg; n = 20) and HR (-25.4 +/- 3.8 beats/min; n = 17) at approximately 74% of the sites stimulated. Intravenous administration of the dopamine D2-receptor antagonist raclopride significantly attenuated both the MAP (70%) and the HR (54%) responses elicited by stimulation of the transitional region where the SNC merges with the lateral VTA (SNC-VTA region). Intravenous administration of the muscarinic receptor blocker atropine methyl bromide had no effect on the magnitude of the MAP and HR responses to stimulation of the SNC-VTA region, whereas administration of the nicotinic receptor blocker hexamethonium bromide significantly attenuated both the depressor and the bradycardic responses. These data suggest that dopaminergic neurons in the SNC-VTA region activate a central pathway that exerts cardiovascular depressor effects that are mediated by the inhibition of sympathetic vasoconstrictor fibers to the vasculature and cardioacceleratory fibers to the heart.

Surround inhibition among projection neurons is weak or nonexistent in the rat neostriatum

1. Antidromic activation of striatal spiny projection neurons by substantia nigra stimulation in vivo did not evoke inhibitory postsynaptic potentials (IPSPs) in the antidromically activated neurons, or in neighboring spiny neurons. 2. More generalized activation of projection cells by stimulation of the efferent pathway in slices did not evoke IPSPs in spiny neurons. Inhibitory mechanisms were operative in these slices, as indicated by the presence of an IPSP component in the orthodromic response to local stimulation. 3. Dual intracellular recordings, obtained from cells located within 50-200 microns of each other in striatal slices also failed to demonstrate any inhibition among striatal spiny cells. Spikes triggered in one spiny neuron by current injection failed to produce any postsynaptic potential in nearby spiny cells at resting or depolarized membrane potentials. Excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation of the cortex were not affected by spiking of neighboring cells. 4. It is impossible to rule out the presence of inhibition among striatal spiny neurons in all circumstances. However, the absence of demonstrable IPSPs in these experiments argue against the common view that mutual inhibition among spiny neurons is a central organizing principle of striatal function.

Excitation by talipexole, a dopamine D 2 agonist, of caudate nucleus neurons activated by nigral stimulation

An electrophysiological study using cats anesthetized with α-chloralose was performed to elucidate whether or not talipexole (B-HT 920 CL 2: 6-allyl-2-amino -5, 6, 7, 8-tetrahydro-4H-thiazolo [4, 5 -d] -azepinedihydrochroride), a dopamine D 2 agonist, acts on postsynaptic dopamine receptors in the caudate nucleus (CN) neurons receiving excitatory input from the pars compacta of substantia nigra (SN). Extracellular neuron activities were recorded in the CN using a glass-insulated silver wire microelectrode attached along a seven-barreled micropipette, each of which was filled with talipexole, quinpirole (dopamine D 2 agonist), domperidone (dopamine D 2 antagonist), glutamate and 2M NaCl. These drugs were microiontophoretically applied to the immediate vicinity of the target neuron. In the same neurons in which the spikes elicited by the SN stimulation were blocked by microiontophoretically applied domperidone, microiontophoretic application of talipexole and quinpirole induced a dose-dependent increase in spontaneous firing. This increase in firing by talipexole and quinpirole was blocked during simultaneous application of domperidone, although glutamate-induced firing remained unaffected by domperidone. In the CN neurons, in which the SN stimulation-induced spikes were not blocked by domperidone, spontaneous firing was not affected by talipexole or quinpirole. These findings suggest that talipexole activates CN neurons receiving a dopaminergic input from SN via D 2 receptors, as does quinpirole.

Ascending and descending convergent inputs to neurons in the nucleus parabrachialis of the rat: an intracellular study

Responses of the nucleus parabrachialis neurons (PBN) to electrical stimulation of the lateral hypothalamus (HL), central nucleus of the amygdala (Ac), dorsolateral funicullus in the spinal cord (SC), mediocaudal nucleus tractus solitarius (NTS), and substantia nigra (SN) were investigated in anesthetized rats by intracellular recording technique. Convergent excitatory postsynaptic potentials (EPSPs) were evoked on 8 of 36 neurons tested by both HL and NTS stimulation. The EPSPs evoked by HL stimulation were characterized as monosynaptic in 4 neurons. The EPSPs evoked by SC stimulation were characterized as monosynaptic in 2 of 36 neurons, moreover, these neurons were also antidromically activated by HL stimulation. Stimulation of Ac evoked EPSPs on 10 of 36 cells tested; 8 demonstrated to be monosynaptic. In addition, IPSP evoked by SN stimulation and EPSP evoked by NTS stimulation converged on three neurons. The results indicate that ascending and descending inputs converge on lateral PBN neurons.

Additivity of nicotinic and muscarinic cholinergic stimulation of substantia nigra.

Microinjection of cholinergic agonists into the anterior substantia nigra increases behaviours for which there is a pre-existing tendency and a low current rate. Rats received microinjections of carbachol, nicotine or a combination of both into the anterior substantia nigra. Carbachol and nicotine both stimulated consumption of palatable food in a dose-dependent manner (F(3,24) = 3.99, p < 0.02 and F(3,33) = 7.07, p < 0.01 respectively). Addition of carbachol to each dose of nicotine caused a significant increase in feeding compared with nicotine alone (F(1,23) = 7.01, p < 0.015). This suggests muscarinic or nicotinic cholinergic stimulation of the anterior substantia nigra can have behaviourally similar effects and, at the doses used here, the effects of nicotinic and muscarinic stimulation are additive.

Suppression of nociceptive responses in parafascicular neurons by stimulation of substantia nigra: an analysis of related inhibitory pathways

A total of 166 neurons in parafascicular nucleus (PF) were studied, 85 from intact animals, 72 following dorsal spinal cord transection (D.Sp.C.X.) and 9 following complete transection of the spinal cord. Two patterns of nociceptive response were identified following noxious stimulation and these responses were classified as ‘nociceptive-off’ and ‘nociceptive-off’ neurons, respectively. The effect of stimulating the substantia nigra (SNS) on the spontaneous and on the nociceptive evoked discharges were observed and compared in intact, D.Sp.C.X. and completely transected spinal cord rats. The results show that SNS significantly suppresses both the spontaneous and the nociceptive evoked discharge elicited by peroneal nerve stimulation. With an intact spinal cord, SNS suppressed both the spontaneous [−37±3.2.% ( P < 0.05)] and the nociceptive evoked discharges [−52.8±2.8% ( P < 0.01)] of the the same stimulation elicited an even more prominent suppression upon both discharges (−4.7.±5.4.%, P < 0.01 and −64.9±5.0%, P < 0.01), respectively. After D.Sp.C.X., the suppressive effects on the ‘nociceptive-on’ cells following SNS were diminished (−28.1±3.5% and −36.9±2.6%, respectively) but not abolished, while in the ‘nociceptive-off’ cells, the inhibitory effects on SNS were unchanged. In addition, the suppressive effects of SNS on the spontaneous activity of PF neurons in cases with completely cut spinal cords remains unchanged. These results suggest that SNS modulates the spontaneous and the noxious evoked responses of the PF neurons by way of supraspinal connections besides the previously described descending projecting pathways.