Branched output neurons of the rat subthalamic nucleus: Electrophysiological study of the synaptic effects on identified cells in the two main target nuclei, the entopeduncular nucleus and the substantia nigra

Hammond, Constance; Shibazaki, Toshio; Rouzaire-Dubois, B.

doi:10.1016/0306-4522(83)90169-0

Cited by 63 publications

(20 citation statements)

References 37 publications

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“…This latency is in good agreement with that previously reported for excitatory responses of nigral neurons to subthalamic stimulation in vivo (Hammond et al 1978(Hammond et al 1983Nakanishi et al 1987). In most cases the onset latency of the DPSP was invariant with changes in stimulus amplitude suggesting that it was monosynaptic (Park 1987).…”

Section: The Response To Stn Stimulation Is a Mixed Epsp-ipspsupporting

confidence: 91%

Subthalamic Stimulation-Induced Synaptic Responses in Substantia Nigra Pars Compacta Dopaminergic Neurons In Vitro

Iribe

Moore

Pang

et al. 1999

Journal of Neurophysiology

106

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Iribe, Yuri, Kevin Moore, Kevin C. H. Pang, and James M. Tepper. Subthalamic stimulation-induced synaptic responses in substantia nigra pars compacta dopaminergic neurons in vitro. J. Neurophysiol. 82: 925-933, 1999. The subthalamic nucleus (STN) is one of the principal sources of excitatory glutamatergic input to dopaminergic neurons of the substantia nigra, yet stimulation of the STN produces both excitatory and inhibitory effects on nigral dopaminergic neurons recorded extracellularly in vivo. The present experiments were designed to determine the sources of the excitatory and inhibitory effects. Synaptic potentials were recorded intracellularly from substantia nigra pars compacta dopaminergic neurons in parasagittal slices in response to stimulation of the STN. Synaptic potentials were analyzed for onset latency, amplitude, duration, and reversal potential in the presence and absence of GABA and glutamate receptor antagonists. STN-evoked depolarizing synaptic responses in dopaminergic neurons reversed at approximately Ϫ31 mV, intermediate between the expected reversal potential for an excitatory and an inhibitory postsynaptic potential (EPSP and IPSP). Blockade of GABA A receptors with bicuculline caused a positive shift in the reversal potential to near 0 mV, suggesting that STN stimulation evoked a near simultaneous EPSP and IPSP. Both synaptic responses were blocked by application of the glutamate receptor antagonist, 6-cyano-7-nitroquinoxalene-2,3-dione. The confounding influence of inhibitory fibers of passage from globus pallidus and/or striatum by STN stimulation was eliminated by unilaterally transecting striatonigral and pallidonigral fibers 3 days before recording. The reversal potential of STN-evoked synaptic responses in dopaminergic neurons in slices from transected animals was approximately Ϫ30 mV. Bath application of bicuculline shifted the reversal potential to ϳ5 mV as it did in intact animals, suggesting that the source of the IPSP was within substantia nigra. These data indicate that electrical stimulation of the STN elicits a mixed EPSP-IPSP in nigral dopaminergic neurons due to the coactivation of an excitatory monosynaptic and an inhibitory polysynaptic connection between the STN and the dopaminergic neurons of substantia nigra pars compacta. The EPSP arises from a direct monosynaptic excitatory glutamatergic input from the STN. The IPSP arises polysynaptically, most likely through STN-evoked excitation of GABAergic neurons in substantia nigra pars reticulata, which produces feed-forward GABA A -mediated inhibition of dopaminergic neurons through inhibitory intranigral axon collaterals.

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Section: The Response To Stn Stimulation Is a Mixed Epsp-ipspsupporting

confidence: 91%

Subthalamic Stimulation-Induced Synaptic Responses in Substantia Nigra Pars Compacta Dopaminergic Neurons In Vitro

Iribe

Moore

Pang

et al. 1999

Journal of Neurophysiology

106

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“…STN DBS has demonstrated to increase neuronal activity of dopamine neurons in the substantia nigra pars compacta (5, 26). Some studies found increased striatal dopamine release in animal models, whereas clinical imaging studies did not support this observation (1,8,18 (14). Electrophysiological studies have demonstrated a decreased activity of substantia nigra pars reticulata neurons by STN DBS (6, 40).The ventral pallidum is connected to the medial STN, which is considered limbic subregion of the STN.…”

Section: Discussionmentioning

confidence: 99%

Deep brain stimulation of the rat subthalamic nucleus induced inhibition of median raphe serotonergic and dopaminergic neurotransmission

Kocabıcak¹,

Jahanshahi²,

Schonfeld³

et al. 2014

Turkish Neurosurgery

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AIm: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) relieves motor dysfunction in advanced Parkinson's disease (PD). However, STN DBS treated patients can experience unpleasant and debilitating psychiatric side effects such as depression and impulsivity. The neural basis of these psychiatric effects has been linked to a dysfunction of 5-hydroxytryptamine (5-HT, serotonin) neurotransmission. STN DBS inhibited activity of 5-HT cell bodies in the dorsal raphe nucleus (DRN). Another important 5-HT source is located in the median raphe nucleus (MRN), which also contains a population of dopamine neurons. The effects of STN DBS on the MRN are unknown. Here, we test the hypothesis that STN DBS reduces 5-HT and dopaminergic function in the MRN, which may contribute to the psychiatric side effects of STN stimulation. mAterIAl and methOds: Bilateral STN DBS was applied in a freely moving rat model. Following STN DBS, rats were sacrificed and the brains were processed for c-Fos, 5-HT and tyrosine hydroxylase (TH) immunohistochemistry. results:We found that STN DBS significantly lowered c-Fos expression compared to non-stimulated controls indicating reduced neuronal activity. Moreover, the mean optical density values of 5-HT and TH cells in the MRN was significantly lower compared to controls. BulGulAr: STN DBS'in, stimüle edilmemiş kontrol grubuyla karşılaştırıldığında c-Fos ekspresyonunu önemli oranda azalttığını tespit ettik. Ayrıca MRN içindeki 5-HT ve TH hücrelerinin ortalama optik dansite değerleri, kontrol grubuyla karşılaştırıldığında oldukça düşüktü.sOnuÇ: Bu sonuçlar, STN DBS'in median raphe nükleusunda 5-HT ve dopamin salınımını inhibe ettiğini göstermektedir.

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“…Classically, neurons in the entopeduncular (EP)/GPi receive excitatory input from the subthalamic nucleus (34). However, in vivo electrophysiological recordings in rodents and cats have revealed that EPh neurons are actually inhibited by stimulation of the subthalamic nucleus (35,36), whereas the majority of EP neurons projecting to the thalamus are indeed excited by this stimulation (35,37,38). These results suggest that as in lamprey, EPh neurons do not receive a direct excitatory input from the subthalamic nucleus but, rather, are inhibited through some unknown pathway.…”

Section: Pallial (Cortical) Projections To the Gph Could Provide Excimentioning

confidence: 99%

Independent circuits in the basal ganglia for the evaluation and selection of actions

Stephenson-Jones

Kardamakis

Robertson

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

116

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The basal ganglia are critical for selecting actions and evaluating their outcome. Although the circuitry for selection is well understood, how these nuclei evaluate the outcome of actions is unknown. Here, we show in lamprey that a separate evaluation circuit, which regulates the habenula-projecting globus pallidus (GPh) neurons, exists within the basal ganglia. The GPh neurons are glutamatergic and can drive the activity of the lateral habenula, which, in turn, provides an indirect inhibitory influence on midbrain dopamine neurons. We show that GPh neurons receive inhibitory input from the striosomal compartment of the striatum. The striosomal input can reduce the excitatory drive to the lateral habenula and, consequently, decrease the inhibition onto the dopaminergic system. Dopaminergic neurons, in turn, provide feedback that inhibits the GPh. In addition, GPh neurons receive direct projections from the pallium (cortex in mammals), which can increase the GPh activity to drive the lateral habenula to increase the inhibition of the neuromodulatory systems. This circuitry, thus, differs markedly from the "direct" and "indirect" pathways that regulate the pallidal (e.g., globus pallidus) output nuclei involved in the control of motion. Our results show that a distinct reward-evaluation circuit exists within the basal ganglia, in parallel to the direct and indirect pathways, which select actions. Our results suggest that these circuits are part of the fundamental blueprint that all vertebrates use to select actions and evaluate their outcome.striosomes | reward/aversion | pallium/cortex | evolution T o achieve a goal, animals need to select actions and evaluate their outcome to determine whether their goal was achieved. In mammals, the basal ganglia play a key role in the selection of actions (1-3) and have more recently been suggested to additionally contribute to predicting and evaluating the outcome of the selected actions (4-8).The so-called "direct" and "indirect" pathways through the basal ganglia are present in all vertebrates and act together to select actions by decreasing tonic inhibition of the basal ganglia output nuclei [globus pallidus interna (GPi) and substantia nigra pars reticulata (SNr)] on a selected motor program and increasing the inhibition onto other competing actions. The output of these selection circuits target brainstem and thalamic motor areas, and neurons within this circuit are modulated by various aspect of movement kinetics related to the initiation and modulation of ongoing actions.In addition to the output neurons that project to motor areas, a separate subpopulation of pallidal neurons projects to the lateral habenula (9-12), a structure involved in evaluating and predicting the motivational value of actions. Recent in vivo recordings in primates have shown that the activity of these habenula-projecting pallidal neurons is modulated by the cues that predict the availability of reward (13,14) and not by aspects of movements. The majority of these pallidal neurons, as with latera...

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Branched output neurons of the rat subthalamic nucleus: Electrophysiological study of the synaptic effects on identified cells in the two main target nuclei, the entopeduncular nucleus and the substantia nigra

Cited by 63 publications

References 37 publications

Subthalamic Stimulation-Induced Synaptic Responses in Substantia Nigra Pars Compacta Dopaminergic Neurons In Vitro

Subthalamic Stimulation-Induced Synaptic Responses in Substantia Nigra Pars Compacta Dopaminergic Neurons In Vitro

Deep brain stimulation of the rat subthalamic nucleus induced inhibition of median raphe serotonergic and dopaminergic neurotransmission

Independent circuits in the basal ganglia for the evaluation and selection of actions

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