scholarly journals Short term depression shapes information transmission in a constitutively active GABAergic synapse

2018 ◽  
Author(s):  
Hagar Lavian ◽  
Alon Korngreen
Keyword(s):  
Basal Ganglia ◽  
Information Transmission ◽  
Globus Pallidus ◽  
Synaptic Depression ◽  
Indirect Pathway ◽  
Short Term ◽  
Gabaergic Synapse ◽  
Firing Rates ◽  
Low Pass ◽  
Constitutively Active

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.

scholarly journals Short-term depression shapes information transmission in a constitutively active GABAergic synapse

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hagar Lavian ◽  
Alon Korngreen
Keyword(s):  
Basal Ganglia ◽  
Information Transmission ◽  
Indirect Pathway ◽  
Short Term ◽  
Gabaergic Synapse ◽  
Pass Filter ◽  
Low Pass Filter ◽  
Whole Cell ◽  
Firing Rates ◽  
Whole Cell Recordings

AbstractShort-term depression is a low-pass filter of synaptic information, reducing synaptic information transfer at high presynaptic firing frequencies. Consequently, during elevated presynaptic firing, little information passes to the postsynaptic neuron. However, many neurons fire at relatively high frequencies all the time. Does depression silence their synapses? We tested this apparent contradiction in the indirect pathway of the basal ganglia. Using numerical modeling and whole-cell recordings from single entopeduncular nucleus (EP) neurons in rat brain slices, we investigated how different firing rates of globus pallidus (GP) neurons affect information transmission to the EP. Whole-cell 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 the integration of multiple inputs, the broad range of GP firing rates would enable different modes of information transmission. 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 depression shapes information transmission in the basal ganglia in particular and via GABAergic synapses in general.

scholarly journals Effects of Dopamine Depletion on Network Entropy in the External Globus Pallidus

2009 ◽  
Vol 102 (2) ◽  
pp. 1092-1102 ◽  
Author(s):  
Ana V. Cruz ◽  
Nicolas Mallet ◽  
Peter J. Magill ◽  
Peter Brown ◽  
Bruno B. Averbeck
Keyword(s):  
Basal Ganglia ◽  
Globus Pallidus ◽  
Dopamine Depletion ◽  
Information Coding ◽  
Logistic Regression Models ◽  
Firing Rates ◽  
Before And After ◽  
Network Entropy ◽  
Coding Capacity

Dopamine depletion in cortical-basal ganglia circuits in Parkinson's disease (PD) grossly disturbs movement and cognition. Classic models relate Parkinsonian dysfunction to changes in firing rates of basal ganglia neurons. However, disturbances in other dynamics of neural activity are also common. Taking both inappropriate firing rates and other dynamics into account and determining how changes in the properties of these neural circuits that occur during PD impact on information coding are thus imperative. Here, we examined in vivo network dynamics in the external globus pallidus (GPe) of rats before and after chronic dopamine depletion. Dopamine depletion led to decreases in the firing rates of GPe neurons and increases in synchronized network oscillations in the β frequency (13–30 Hz) band. Using logistic regression models, we determined the combined and separate impacts of these factors on network entropy, a measure of the upper bound of information coding capacity. Importantly, changes in these features in dopamine-depleted rats led to a significant decrease in GPe network entropy. Changes in firing rates had the largest impact on entropy, with changes in synchrony also decreasing entropy at the network level. Changes in autocorrelations tended to offset these effects because autocorrelations decreased entropy more in the control animals. Thus it is possible that reduced information coding capacity within basal ganglia networks may contribute to the behavioral deficits accompanying PD.

scholarly journals Endocannabinoids and Dopamine Balance Basal Ganglia Output

2021 ◽  
Vol 15 ◽  
Author(s):  
Lilach Gorodetski ◽  
Yocheved Loewenstern ◽  
Anna Faynveitz ◽  
Izhar Bar-Gad ◽  
Kim T. Blackwell ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Globus Pallidus ◽  
Control Unit ◽  
Vital Role ◽  
Primary Afferents ◽  
Entopeduncular Nucleus ◽  
Indirect Pathway ◽  
Relay Nucleus ◽  
Prevailing View

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.

scholarly journals Activation of the basal ganglia and indirect pathway neurons during frontal lobe seizures

Brain ◽  
2021 ◽  
Author(s):  
Anastasia Brodovskaya ◽  
Shinnosuke Shiono ◽  
Jaideep Kapur
Keyword(s):  
Basal Ganglia ◽  
Substantia Nigra ◽  
Frontal Lobe ◽  
Globus Pallidus ◽  
Subthalamic Nucleus ◽  
D2 Receptor ◽  
Field Potential ◽  
Anticonvulsant Effect ◽  
Neuronal Activation ◽  
Indirect Pathway

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.

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

2019 ◽  
Author(s):  
Hidetoshi Amita ◽  
Okihide Hikosaka
Keyword(s):  
Basal Ganglia ◽  
Globus Pallidus ◽  
Real Life ◽  
Inhibitory Response ◽  
Choice Task ◽  
Local Injection ◽  
Indirect Pathway ◽  
Rejection Mechanism ◽  
Goal Directed Behavior ◽  
Globus Pallidus Externus

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.

scholarly journals Deep Brain Stimulation Reduces Neuronal Entropy in the MPTP-Primate Model of Parkinson's Disease

2008 ◽  
Vol 100 (5) ◽  
pp. 2807-2818 ◽  
Author(s):  
Alan D. Dorval ◽  
Gary S. Russo ◽  
Takao Hashimoto ◽  
Weidong Xu ◽  
Warren M. Grill ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Basal Ganglia ◽  
Globus Pallidus ◽  
Neuronal Activity ◽  
Firing Pattern ◽  
Neuronal Firing ◽  
Motor Symptoms ◽  
Firing Rates ◽  
Frequency Stimulation ◽  
Motor Thalamus

High-frequency stimulation (HFS) of the subthalamic nucleus (STN) or internal segment of the globus pallidus is a clinically successful treatment for the motor symptoms of Parkinson's disease. However, the mechanisms by which HFS alleviates these symptoms are not understood. Whereas initial studies focused on HFS-induced changes in neuronal firing rates, recent studies suggest that changes in patterns of neuronal activity may correlate with symptom alleviation. We hypothesized that effective STN HFS reduces the disorder of neuronal firing patterns in the basal ganglia thalamic circuit, minimizing the pathological activity associated with parkinsonism. Stimulating leads were implanted in the STN of two rhesus monkeys rendered parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Action potentials were recorded from neurons of the internal and external globus pallidus and the motor thalamus (ventralis anterior, ventralis lateralis pars oralis, and ventralis posterior lateralis pars oralis) during HFS that reduced motor symptoms and during clinically ineffective low-frequency stimulation (LFS). Firing pattern entropy was calculated from the recorded spike times to quantify the disorder of the neuronal activity. The firing pattern entropy of neurons within each region of the pallidum and motor thalamus decreased in response to HFS ( n ≥ 18 and P ≤ 0.02 in each region), whereas firing rate changes were specific to pallidal neurons only. In response to LFS, firing rates were unchanged, but firing pattern entropy increased throughout the circuit ( n ≥ 24 and P ≤ 10−4 in each region). These data suggest that the clinical effectiveness of HFS is correlated with, and potentially mediated by, a regularization of the pattern of neuronal activity throughout the basal ganglia thalamic circuit.

Model and Analysis for the Onset of Parkinsonian Firing Patterns in a Simplified Basal Ganglia

2019 ◽  
Vol 29 (01) ◽  
pp. 1850021 ◽  
Author(s):  
Michael Caiola ◽  
Mark H. Holmes
Keyword(s):  
Basal Ganglia ◽  
Globus Pallidus ◽  
Neurological Disease ◽  
Time Delays ◽  
Closed Loop ◽  
Dopamine Depletion ◽  
Beta Oscillations ◽  
Firing Rates ◽  
Internal Loop ◽  
Globus Pallidus Internal

Parkinson’s disease (PD) is a degenerative neurological disease that disrupts the movement cycle in the basal ganglia. As the disease progresses, dopamine depletion leads to changes to how the basal ganglia functions as well as the appearance of abnormal beta oscillations. There is much debate on just exactly how these connection strengths change and just how the oscillations emerge. One leading hypothesis claims that the oscillations develop in the globus pallidus external, subthalamic nucleus, and globus pallidus internal loop. We introduce a mathematical model that calculates the average firing rates of this loop while still accounting for the larger closed loop of the entire basal ganglia system. This model is constructed such that physiologically realistic results can be obtained while not sacrificing the use of analytic methods. Because of this, it is possible to determine how the change in the connection strengths can drive the necessary changes in firing rates seen in recordings and account for the generation of trademark beta oscillations of PD without relying on highly specific time delays, stochastic approaches, or numerical approximations. Additionally, we find that the entire cortico-basal ganglia-thalamo-cortical loop is essential for abnormal oscillations to originate.

scholarly journals Morphological Abnormalities in the Basal Ganglia of Dystonia Patients

2021 ◽  
pp. 1-12
Author(s):  
Xi Bai ◽  
Peter Vajkoczy ◽  
Katharina Faust
Keyword(s):  
Basal Ganglia ◽  
Globus Pallidus ◽  
Trajectory Planning ◽  
Matched Control ◽  
Young Patients ◽  
Control Population ◽  
Pathogenic Role ◽  
Target Region ◽  
Morphological Abnormalities ◽  
Primary Dystonia

<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.

scholarly journals 18F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging evaluation of chorea

2018 ◽  
Vol 10 (3) ◽  
Author(s):  
Nobuyuki Ishii ◽  
Hitoshi Mochizuki ◽  
Miyuki Miyamoto ◽  
Yuka Ebihara ◽  
Kazutaka Shiomi ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Positron Emission Tomography ◽  
Basal Ganglia ◽  
Magnetic Resonance ◽  
Emission Tomography ◽  
Fluorodeoxyglucose Positron Emission Tomography ◽  
Resonance Imaging ◽  
Indirect Pathway ◽  
Positron Emission ◽  
Fluorodeoxyglucose Positron Emission

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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