scholarly journals An open cortico-basal ganglia loop allows limbic control over motor output via the nigrothalamic pathway

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Sho Aoki ◽  
Jared B Smith ◽  
Hao Li ◽  
Xunyi Yan ◽  
Masakazu Igarashi ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Ventral Striatum ◽  
Motor Output ◽  
Functional Domain ◽  
Closed Loops ◽  
Dorsolateral Striatum ◽  
Parallel Circuits ◽  
Motor Loop ◽  
Motor Thalamus

Cortico-basal ganglia-thalamocortical loops are largely conceived as parallel circuits that process limbic, associative, and sensorimotor information separately. Whether and how these functionally distinct loops interact remains unclear. Combining genetic and viral approaches, we systemically mapped the limbic and motor cortico-basal ganglia-thalamocortical loops in rodents. Despite largely closed loops within each functional domain, we discovered a unidirectional influence of the limbic over the motor loop via ventral striatum-substantia nigra (SNr)-motor thalamus circuitry. Slice electrophysiology verifies that the projection from ventral striatum functionally inhibits nigro-thalamic SNr neurons. In vivo optogenetic stimulation of ventral or dorsolateral striatum to SNr pathway modulates activity in medial prefrontal cortex (mPFC) and motor cortex (M1), respectively. However, whereas the dorsolateral striatum-SNr pathway exerts little impact on mPFC, activation of the ventral striatum-SNr pathway effectively alters M1 activity. These results demonstrate an open cortico-basal ganglia loop whereby limbic information could modulate motor output through ventral striatum control of M1.

scholarly journals Revisiting the “Paradox of Stereotaxic Surgery”: Insights Into Basal Ganglia-Thalamic Interactions

2021 ◽  
Vol 15 ◽  
Author(s):  
Jennifer L. Magnusson ◽  
Daniel K. Leventhal
Keyword(s):  
Basal Ganglia ◽  
Movement Disorders ◽  
Motor Output ◽  
Clinical Effects ◽  
Stereotaxic Surgery ◽  
Standard Rate ◽  
Standard Models ◽  
Cortical Physiology ◽  
Motor Thalamus ◽  
Deep Brain

Basal ganglia dysfunction is implicated in movement disorders including Parkinson Disease, dystonia, and choreiform disorders. Contradicting standard “rate models” of basal ganglia-thalamic interactions, internal pallidotomy improves both hypo- and hyper-kinetic movement disorders. This “paradox of stereotaxic surgery” was recognized shortly after rate models were developed, and is underscored by the outcomes of deep brain stimulation (DBS) for movement disorders. Despite strong evidence that DBS activates local axons, the clinical effects of lesions and DBS are nearly identical. These observations argue against standard models in which GABAergic basal ganglia output gates thalamic activity, and raise the question of how lesions and stimulation can have similar effects. These paradoxes may be resolved by considering thalamocortical loops as primary drivers of motor output. Rather than suppressing or releasing cortex via motor thalamus, the basal ganglia may modulate the timing of thalamic perturbations to cortical activity. Motor cortex exhibits rotational dynamics during movement, allowing the same thalamocortical perturbation to affect motor output differently depending on its timing with respect to the rotational cycle. We review classic and recent studies of basal ganglia, thalamic, and cortical physiology to propose a revised model of basal ganglia-thalamocortical function with implications for basic physiology and neuromodulation.

scholarly journals Anatomical localization of Cav3.1 calcium channels and electrophysiological effects of T-type calcium channel blockade in the motor thalamus of MPTP-treated monkeys

2016 ◽  
Vol 115 (1) ◽  
pp. 470-485 ◽  
Author(s):  
Annaelle Devergnas ◽  
Erdong Chen ◽  
Yuxian Ma ◽  
Ikuma Hamada ◽  
Damien Pittard ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Calcium Channels ◽  
Calcium Channel ◽  
Oscillatory Activity ◽  
Electron Microscopic Level ◽  
Dopamine Depletion ◽  
Frequency Range ◽  
Electron Microscopic ◽  
Motor Thalamus

Conventional anti-Parkinsonian dopamine replacement therapy is often complicated by side effects that limit the use of these medications. There is a continuing need to develop nondopaminergic approaches to treat Parkinsonism. One such approach is to use medications that normalize dopamine depletion-related firing abnormalities in the basal ganglia-thalamocortical circuitry. In this study, we assessed the potential of a specific T-type calcium channel blocker (ML218) to eliminate pathologic burst patterns of firing in the basal ganglia-receiving territory of the motor thalamus in Parkinsonian monkeys. We also carried out an anatomical study, demonstrating that the immunoreactivity for T-type calcium channels is strongly expressed in the motor thalamus in normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. At the electron microscopic level, dendrites accounted for >90% of all tissue elements that were immunoreactive for voltage-gated calcium channel, type 3.2-containing T-type calcium channels in normal and Parkinsonian monkeys. Subsequent in vivo electrophysiologic studies in awake MPTP-treated Parkinsonian monkeys demonstrated that intrathalamic microinjections of ML218 (0.5 μl of a 2.5-mM solution, injected at 0.1–0.2 μl/min) partially normalized the thalamic activity by reducing the proportion of rebound bursts and increasing the proportion of spikes in non-rebound bursts. The drug also attenuated oscillatory activity in the 3–13-Hz frequency range and increased gamma frequency oscillations. However, ML218 did not normalize Parkinsonism-related changes in firing rates and oscillatory activity in the beta frequency range. Whereas the described changes are promising, a more complete assessment of the cellular and behavioral effects of ML218 (or similar drugs) is needed for a full appraisal of their anti-Parkinsonian potential.

scholarly journals Basal ganglia and cortical control of thalamic rebound spikes

2018 ◽  
Author(s):  
Mohammadreza Mohagheghi Nejad ◽  
Stefan Rotter ◽  
Robert Schmidt
Keyword(s):  
Basal Ganglia ◽  
Neural Activity ◽  
Output Neurons ◽  
Cortical Excitation ◽  
Sensory Responses ◽  
Rebound Spiking ◽  
Motor Thalamus ◽  
The Impact ◽  
Motor Signals

AbstractBasal ganglia output neurons transmit motor signals by decreasing their firing rate during movement. This decrease can lead to post-inhibitory rebound spikes in thalamocortical neurons in motor thalamus. While in healthy animals neural activity in the basal ganglia is markedly uncorrelated, in Parkinson’s disease neural activity becomes pathologically correlated. Here we investigated the impact of correlations in the basal ganglia output on the transmission of motor signals to motor thalamus using a Hodgkin-Huxley model of a thalamocortical neuron. We found that correlations in the basal ganglia output disrupt the transmission of motor signals via rebound spikes by decreasing the signal-to-noise ratio and increasing the trial-to-trial variability. We further examined the role of brief sensory responses in basal ganglia output neurons and the effect of cortical excitation of motor thalamus in modulating rebound spiking. Interestingly, both the sensory responses and cortical inputs could either promote or suppress the generation of rebound spikes depending on their timing relative to the motor signal. Finally, in the model rebound spiking occurred despite the presence of moderate levels of excitation, indicating that rebound spiking might be feasible in a parameter regime relevant also in vivo. Overall, our model provides novel insights into the transmission of motor signals from the basal ganglia to motor thalamus by suggesting new functional roles for active decorrelation and sensory responses in the basal ganglia, as well as cortical excitation of motor thalamus.

scholarly journals Dopamine D2/3 Receptor Availabilities and Evoked Dopamine Release in Striatum Differentially Predict Impulsivity and Novelty Preference in Roman High- and Low-Avoidance Rats

2020 ◽  
Author(s):  
Lidia Bellés ◽  
Andrea Dimiziani ◽  
Stergios Tsartsalis ◽  
Philippe Millet ◽  
François R Herrmann ◽  
...  
Keyword(s):  
Ventral Striatum ◽  
Single Photon ◽  
Ex Vivo ◽  
Photon Emission ◽  
Dorsal Striatum ◽  
Reaction Time Task ◽  
Emission Computed Tomography ◽  
Novelty Preference ◽  
Da Release

Abstract Background Impulsivity and novelty preference are both associated with an increased propensity to develop addiction-like behaviors, but their relationship and respective underlying dopamine (DA) underpinnings are not fully elucidated. Methods We evaluated a large cohort (n = 49) of Roman high- and low-avoidance rats using single photon emission computed tomography to concurrently measure in vivo striatal D2/3 receptor (D2/3R) availability and amphetamine (AMPH)-induced DA release in relation to impulsivity and novelty preference using a within-subject design. To further examine the DA-dependent processes related to these traits, midbrain D2/3-autoreceptor levels were measured using ex vivo autoradiography in the same animals. Results We replicated a robust inverse relationship between impulsivity, as measured with the 5-choice serial reaction time task, and D2/3R availability in ventral striatum and extended this relationship to D2/3R levels measured in dorsal striatum. Novelty preference was positively related to impulsivity and showed inverse associations with D2/3R availability in dorsal striatum and ventral striatum. A high magnitude of AMPH-induced DA release in striatum predicted both impulsivity and novelty preference, perhaps owing to the diminished midbrain D2/3-autoreceptor availability measured in high-impulsive/novelty-preferring Roman high-avoidance animals that may amplify AMPH effect on DA transmission. Mediation analyses revealed that while D2/3R availability and AMPH-induced DA release in striatum are both significant predictors of impulsivity, the effect of striatal D2/3R availability on novelty preference is fully mediated by evoked striatal DA release. Conclusions Impulsivity and novelty preference are related but mediated by overlapping, yet dissociable, DA-dependent mechanisms in striatum that may interact to promote the emergence of an addiction-prone phenotype.

Neurotransmitters in the Basal Ganglia and Motor Thalamus: Their Role for the Regulation of Muscle Tone

1987 ◽  
pp. 185-202 ◽  
Author(s):  
T. Klockgether ◽  
M. Schwarz ◽  
L. Turski ◽  
C. Ikonomidou-Turski ◽  
K. Ossowska ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Muscle Tone ◽  
Motor Thalamus

Pathology, Phenomenology and the Dopamine Hypothesis of Schizophrenia

1987 ◽  
Vol 151 (3) ◽  
pp. 288-301 ◽  
Author(s):  
P. J. McKenna
Keyword(s):  
Prefrontal Cortex ◽  
Basal Ganglia ◽  
Functional Role ◽  
Ventral Striatum ◽  
Brain Structures ◽  
Schizophrenic Symptom ◽  
Dopamine Hypothesis ◽  
Dopamine Innervation

The dopamine hypothesis of schizophrenia implies that positive schizophrenic symptoms should be understandable by reference to brain structures receiving a dopamine innervation, or in terms of the functional role of dopamine itself. The basal ganglia, ventral striatum, septo-hippocampal system, and prefrontal cortex, sites of mesotelencephalic dopamine innervation, are examined and it is argued that their dysfunction could form the basis of particular schizophrenic symptom classes. The postulated involvement of dopamine in reinforcement processes might further assist such interpretations. This type of analysis can be extended to other categories of schizophrenic psychopathology.

Glutamate Neurotransmission Is Not Required for, But May Modulate, Hypoxic Sensitivity of Pre-Bötzinger Complex In Vivo

2005 ◽  
Vol 93 (3) ◽  
pp. 1278-1284 ◽  
Author(s):  
Irene C. Solomon
Keyword(s):  
Phrenic Nerve ◽  
Excitatory Amino Acid ◽  
Glutamate Release ◽  
Receptor Activation ◽  
Motor Output ◽  
Induced Response ◽  
Homocysteic Acid ◽  
Bötzinger Complex ◽  
Nerve Discharge

Focal hypoxia in the pre-Bötzinger complex (pre-BötC) in vivo elicits excitation of inspiratory motor output by modifying the patterning and timing of phrenic bursts. Hypoxia, however, has been reported to enhance glutamate release in some regions of the brain, including the medullary ventral respiratory column; thus the pre-BötC–mediated hypoxic respiratory excitation may result from, or be influenced by, hypoxia-induced activation of ionotropic glutamate [i.e., excitatory amino acid (EAA)] receptors. To test this possibility, the effects of focal pre-BötC hypoxia [induced by sodium cyanide (NaCN)] were examined before and after blockade of ionotropic EAA receptors [using kynurenic acid (KYN)] in this region in chloralose-anesthetized, vagotomized, mechanically ventilated cats. Before blockade of ionotropic EAA receptors, unilateral microinjection of NaCN (1 mM; 10–20 nl) into the pre-BötC produced either phasic or tonic excitation of phrenic nerve discharge. Unilateral microinjection of KYN (50–100 mM; 40 nl) decreased the amplitude and frequency of basal phrenic nerve discharge; however, subsequent microinjection of NaCN, but not dl-homocysteic acid (DLH, a glutamate analog), still produced excitation of phrenic motor output. Under these conditions, the NaCN-induced excitation included frequency modulation (FM) of phasic phrenic bursts, and in many cases, augmented and/or fractionated phrenic bursts. These findings show that the hypoxia-sensing function of the in vivo pre-BötC, which produces excitation of phrenic nerve discharge, is not dependent on activation of ionotropic glutamate receptors, but ionotropic glutamate receptor activation may modify the expression of the focal hypoxia-induced response. Thus these findings provide additional support to the concept of intrinsic hypoxic sensitivity of the pre-BötC.

scholarly journals Changes in excitability properties of ventromedial motor thalamic neurons in 6-OHDA lesioned mice

2020 ◽  
Author(s):  
Edyta K Bichler ◽  
Francesco Cavarretta ◽  
Dieter Jaeger
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Potassium Current ◽  
Cellular Level ◽  
Inhibitory Input ◽  
Dopamine Depletion ◽  
Thalamic Nuclei ◽  
Adult Mice ◽  
Motor Thalamus

AbstractThe activity of basal ganglia input receiving motor thalamus (BGMT) makes a critical impact on motor cortical processing, but modification in BGMT processing with Parkinsonian conditions have not be investigated at the cellular level. Such changes may well be expected due to homeostatic regulation of neural excitability in the presence of altered synaptic drive with dopamine depletion. We addressed this question by comparing BGMT properties in brain slice recordings between control and unilaterally 6-OHDA treated adult mice. At a minimum of 1 month post 6-OHDA treatment, BGMT neurons showed a highly significant increase in intrinsic excitability, which was primarily due to a decrease in M-type potassium current. BGMT neurons after 6-OHDA treatment also showed an increase in T-type calcium rebound spikes following hyperpolarizing current steps. Biophysical computer modeling of a thalamic neuron demonstrated that an increase in rebound spiking can also be accounted for by a decrease in the M-type potassium current. Modeling also showed that an increase in sag with hyperpolarizing steps found after 6-OHDA treatment could in part but not fully be accounted for by the decrease in M-type current. These findings support the hypothesis that homeostatic changes in BGMT neural properties following 6-OHDA treatment likely influence the signal processing taking place in basal ganglia thalamocortical processing in Parkinson’s disease.Significance StatementOur investigation of the excitability properties of neurons in the basal ganglia input receiving motor thalamus (BGMT) is significant because they are likely to be different from properties in other thalamic nuclei due to the additional inhibitory input stream these neurons receive. Further, they are important to understand the role of BGMT in the dynamic dysfunction of cortico – basal ganglia circuits in Parkinson’s disease. We provide clear evidence that after 6-OHDA treatment of mice important homeostatic changes occur in the intrinsic properties of BGMT neurons. Specifically we identify the M-type potassium current as an important thalamic excitability regulator in the parkinsonian state.

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