scholarly journals Indirect pathway of caudate tail for choosing good objects in periphery

2019 ◽  
Author(s):  
Hidetoshi Amita ◽  
Okihide Hikosaka

AbstractChoosing good objects is essential for real life, which is controlled mainly by the basal ganglia. For that, a subject need to not only find good objects, but ‘reject’ bad objects. To reveal this ‘rejection’ mechanism, we created a sequential saccade choice task for monkeys and studied the indirect pathway of caudate tail mediated by cvGPe (caudal-ventral globus pallidus externus). The inhibitory responses of cvGPe neurons to bad objects were smaller when the monkey made saccades to them by mistake. Moreover, experimental reduction of the inhibitory response by local injection of bicuculline (GABAA antagonist) disabled the monkey to reject bad objects. In conclusion, rejecting bad objects is crucial for goal-directed behavior, which is controlled by the indirect pathway in the basal ganglia.

2019 ◽  
Vol 5 (8) ◽  
pp. eaaw9297 ◽  
Author(s):  
Hidetoshi Amita ◽  
Okihide Hikosaka

The essential everyday task of making appropriate choices is a process controlled mainly by the basal ganglia. To this end, subjects need not only to find “good” objects in their environment but also to reject “bad” objects. To reveal this rejection mechanism, we created a sequential saccade choice task for monkeys and studied the role of the indirect pathway from the CDt (tail of the caudate nucleus) mediated by cvGPe (caudal-ventral globus pallidus externus). Neurons in cvGPe were typically inhibited by the appearance of bad objects; however, this inhibition was reduced on trials when the monkeys made undesired saccades to the bad objects. Moreover, disrupting the inhibitory influence of CDt on cvGPe by local injection of bicuculline (GABAA receptor antagonist) impaired the monkeys’ ability to suppress saccades to bad objects. Thus, the indirect pathway mediates the rejection of bad choices, a crucial component of goal-directed behavior.


2021 ◽  
Vol 15 ◽  
Author(s):  
Lilach Gorodetski ◽  
Yocheved Loewenstern ◽  
Anna Faynveitz ◽  
Izhar Bar-Gad ◽  
Kim T. Blackwell ◽  
...  

The entopeduncular nucleus is one of the basal ganglia's output nuclei, thereby controlling basal ganglia information processing. Entopeduncular nucleus neurons integrate GABAergic inputs from the Striatum and the globus pallidus, together with glutamatergic inputs from the subthalamic nucleus. We show that endocannabinoids and dopamine interact to modulate the long-term plasticity of all these primary afferents to the entopeduncular nucleus. Our results suggest that the interplay between dopamine and endocannabinoids determines the balance between direct pathway (striatum) and indirect pathway (globus pallidus) in entopeduncular nucleus output. Furthermore, we demonstrate that, despite the lack of axon collaterals, information is transferred between neighboring neurons in the entopeduncular nucleus via endocannabinoid diffusion. These results transform the prevailing view of the entopeduncular nucleus as a feedforward “relay” nucleus to an intricate control unit, which may play a vital role in the process of action selection.


2018 ◽  
Author(s):  
Hagar Lavian ◽  
Alon Korngreen

AbstractShort-term depression is a low pass filter of synaptic information that reduces and flattens synaptic information transfer at high presynaptic firing frequencies. This view questions the relevance of spontaneous high firing rates in some networks. In the indirect pathway of the basal ganglia, spontaneously active neurons in the globus pallidus (GP) form depressing inhibitory synapses in the basal ganglia output nuclei. Using numerical modeling and whole-cell recordings from single entopeduncular nucleus (EP) neurons in rat brain slices we investigated the contribution of the different firing rates of GP neurons to information transmission in the indirect pathway. Wholecell recordings showed significant variability in steady-state depression which decreased as stimulation frequency increased. Modeling predicted that this variability would translate into different postsynaptic noise levels during constitutive presynaptic activity. Our simulations further predicted that individual GP-EP synapses mediate gain control. However, when we consider integration of multiple inputs, the large range of GP firing rates would enable different modes of information transmission in which the magnitude and temporal features of postsynaptic modulation would change as a function of present and past firing rates of GP neurons. Finally, we predict that changes in dopamine levels can shift the action of GP neurons from rate coding to gain modulation. Our results thus demonstrate how short-term synaptic depression shapes information transmission in the basal ganglia in particular and via GABAergic synapses in general.Significant statementSynapses displaying short-term depression are low-pass filters of synaptic input. Consequently, when presynaptic firing is high, little information passes to the postsynaptic neuron. However, many neurons fire at relatively high frequencies all the time. Are their synapses constantly silenced by depression? We tested this apparent contradiction in the indirect pathway of the basal ganglia, where neurons from the globus pallidus (GP) form constitutively active depressing synapses on basal ganglia output. We hypothesized that the different rates of ongoing activity underlie different modes of action for GP neurons. We show that the synaptic and structural properties of the indirect pathway map GP baseline frequencies to different postsynaptic signals, thus demonstrating how short-term synaptic depression shapes information transmission in the basal ganglia.


Cureus ◽  
2020 ◽  
Author(s):  
Paul Saad ◽  
Karina S Shendrik ◽  
Paul J Karroum ◽  
Heela Azizi ◽  
Ayodeji Jolayemi

2018 ◽  
Author(s):  
Arpiar Saunders ◽  
Evan Macosko ◽  
Alec Wysoker ◽  
Melissa Goldman ◽  
Fenna Krienen ◽  
...  

The mammalian brain is composed of diverse, specialized cell populations, few of which we fully understand. To more systematically ascertain and learn from cellular specializations in the brain, we used Drop-seq to perform single-cell RNA sequencing of 690,000 cells sampled from nine regions of the adult mouse brain: frontal and posterior cortex (156,000 and 99,000 cells, respectively), hippocampus (113,000), thalamus (89,000), cerebellum (26,000), and all of the basal ganglia – the striatum (77,000), globus pallidus externus/nucleus basalis (66,000), entopeduncular/subthalamic nuclei (19,000), and the substantia nigra/ventral tegmental area (44,000). We developed computational approaches to distinguish biological from technical signals in single-cell data, then identified 565 transcriptionally distinct groups of cells, which we annotate and present through interactive online software we developed for visualizing and re-analyzing these data (DropViz). Comparison of cell classes and types across regions revealed features of brain organization. These included a neuronal gene-expression module for synthesizing axonal and presynaptic components; widely shared patterns in the combinatorial co-deployment of voltage-gated ion channels by diverse neuronal populations; functional distinctions among cells of the brain vasculature; and specialization of glutamatergic neurons across cortical regions to a degree not observed in other neuronal or non-neuronal populations. We describe systematic neuronal classifications for two complex, understudied regions of the basal ganglia, the globus pallidus externus and substantia nigra reticulata. In the striatum, where neuron types have been intensely researched, our data reveal a previously undescribed population of striatal spiny projection neurons (SPNs) comprising 4% of SPNs. The adult mouse brain cell atlas can serve as a reference for analyses of development, disease, and evolution.


Brain ◽  
2021 ◽  
Author(s):  
Anastasia Brodovskaya ◽  
Shinnosuke Shiono ◽  
Jaideep Kapur

Abstract There are no detailed descriptions of neuronal circuit active during frontal lobe motor seizures. Using activity reporter mice, local field potential recordings, tissue clearing, viral tracing, and super-resolution microscopy, we found neuronal activation after focal motor to bilateral tonic-clonic seizures in the striatum, globus pallidus externus, subthalamic nucleus, substantia nigra pars reticulata and neurons of the indirect pathway. Seizures preferentially activated dopamine D2 receptor-expressing neurons over D1 in the striatum, which have different projections. Furthermore, the D2 receptor agonist infused into the striatum exerted an anticonvulsant effect. Seizures activate structures via short and long latency loops, and anatomical connections of the seizure focus determine the seizure circuit. These studies, for the first time, show activation of neurons in the striatum, globus pallidus, subthalamic nucleus, and substantia nigra during frontal lobe motor seizures on the cellular level, revealing a complex neuronal activation circuit subject to modulation by the basal ganglia.


2021 ◽  
Author(s):  
Rosa Mastrogiacomo ◽  
Gabriella Trigilio ◽  
Daniel Dautan ◽  
Celine Devroye ◽  
Valentina Ferretti ◽  
...  

Astrocytic involvement in dopamine dynamics related to motivational and sensorimotor gating abilities is unknown. We found that dysbindin-1 (Dys1) hypofunction increases the activity of as-trocytes, which express only the isoform Dys1A that is reduced in the caudate of patients with schizophrenia. Astrocytic Dys1A disruption resulted in avolition and sensorimotor gating deficits, increased astrocytic dopamine D2 receptors and decreased dopaminergic tone within basal gan-glia. Notably, astrocytic Dys1A hypofunction disrupted dopamine dynamics linked to reward ex-pectancy and interconnected with astrocytes Ca2+ responses mainly in the globus pallidus externus (GPe). Finally, we proved these phenotypes were mediated by D2 receptors in astrocytes as their selective deletion in astrocytes either in GPe or SNc/VTA enhanced motivation and sensorimotor gating abilities as well as dopaminergic release in the GPe. Therefore, astrocytes control motivational and sensorimotor gating processes through Dys1A/D2-dependent mechanisms within the basal ganglia.


2020 ◽  
Vol 13 (2) ◽  
pp. 158-175 ◽  
Author(s):  
Graham Pluck ◽  
Cristina Crespo-Andrade ◽  
Patricia Parreño ◽  
Karla I. Haro ◽  
María A. Martínez ◽  
...  

2021 ◽  
pp. 1-12
Author(s):  
Xi Bai ◽  
Peter Vajkoczy ◽  
Katharina Faust

<b><i>Objective:</i></b> The pathophysiology of dystonia is poorly understood. As opposed to secondary forms of dystonia, primary dystonia has long been believed to lack any neuroanatomical substrate. During trajectory planning for DBS, however, conspicuous T2-hyperinstensive signal alterations (SA) were registered within the target region, even in young patients, where ischemia is rare. <b><i>Methods:</i></b> Fifty MRIs of primary dystonia patients scheduled for DBS were analyzed. Total basal ganglia (BG) volumes, as well as proportionate SA volumes, were measured and compared to 50 age-matched control patients. <b><i>Results:</i></b> There was a 10-fold preponderance of percentaged SA within the globus pallidus (GP) in dystonia patients. The greatest disparity was in young patients &#x3c;25 years. Also, total BG volume differences were observed with larger GP and markedly smaller putamen and caudate in the dystonia group. <b><i>Conclusions:</i></b> BG morphology in primary dystonia differed from a control population. Volume reductions of the putamen and caudate may reflect functional degeneration, while volume increases of the GP may indicate overactivity. T2-hyperintensive SA in the GP of young primary dystonia patients, where microvascular lesions are highly unlikely, are striking. Their pathogenic role remains unclear.


2018 ◽  
Vol 10 (3) ◽  
Author(s):  
Nobuyuki Ishii ◽  
Hitoshi Mochizuki ◽  
Miyuki Miyamoto ◽  
Yuka Ebihara ◽  
Kazutaka Shiomi ◽  
...  

Chorea is thought to be caused by deactivation of the indirect pathway in the basal ganglia circuit. However, few imaging studies have evaluated the basal ganglia circuit in actual patients with chorea. We investigated the lesions and mechanisms underlying chorea using brain magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). This retrospective case series included three patients with chorea caused by different diseases: hyperglycemic chorea, Huntington’s disease, and subarachnoid hemorrhage. All the patients showed dysfunction in the striatum detected by both MRI and FDG-PET. These neuroimaging findings confirm the theory that chorea is related to an impairment of the indirect pathway of basal ganglia circuit.


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