Neurochemical Oscillations in the Basal Ganglia

Noori, Hamid; Jäger, Willi

doi:10.1007/s11538-009-9441-7

Cited by 10 publications

(10 citation statements)

References 56 publications

(51 reference statements)

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“…In particular, in silico investigations of drug‐induced molecular and physiological alterations within the brain are helpful in understanding disease progression and pharmacological treatment efficacy. Various mathematical models have already been developed to describe the dynamics of molecular and physiological processes within the brain (Durstewitz, Kelc & Güntürkün ; Ahmed, Bobashev & Gutkin ; Kobayashi & Schultz ; Noori & Jager ; Noori ), but these models are confronted with similar difficulties: the complexity of brain tissue and neuronal connectivity. Thus, mathematicians are forced to restrict their models to either single‐cell properties, small neuronal networks or simplified brain region networks (Cervantes & Fraguela Collar ; Cohen & Frank ).…”

Section: Discussionmentioning

confidence: 99%

“…As opportunities to use and abuse drugs have increased dramatically during the past 50 years, so has addiction research. A systematic review on publication trends in the addiction research field also indicates the increasing application of neurocomputational methods (Chen ; Ahmed & Koob ; Gutkin, Dehaene & Changeux ; Bobashev, Costenbader & Gutkin ; Noori & Jäger ; Helinski & Spanagel ; Noori ; Noori ). These models deal with molecular processes at the system level and as such require essential information on large‐scale brain topology, in terms of regional connectivities and neurochemical localizations.…”

Section: Introductionmentioning

confidence: 99%

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Neurocircuitry for modeling drug effects

2012

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The identification and functional understanding of the neurocircuitry that mediates alcohol and drug effects that are relevant for the development of addictive behavior is a fundamental challenge in addiction research. Here we introduce an assumption-free construction of a neurocircuitry that mediates acute and chronic drug effects on neurotransmitter dynamics that is solely based on rodent neuroanatomy. Two types of data were considered for constructing the neurocircuitry: (1) information on the cytoarchitecture and neurochemical connectivity of each brain region of interest obtained from different neuroanatomical techniques; (2) information on the functional relevance of each region of interest with respect to alcohol and drug effects. We used mathematical data mining and hierarchical clustering methods to achieve the highest standards in the preprocessing of these data. Using this approach, a dynamical network of high molecular and spatial resolution containing 19 brain regions and seven neurotransmitter systems was obtained. Further graph theoretical analysis suggests that the neurocircuitry is connected and cannot be separated into further components. Our analysis also reveals the existence of a principal core subcircuit comprised of nine brain regions: the prefrontal cortex, insular cortex, nucleus accumbens, hypothalamus, amygdala, thalamus, substantia nigra, ventral tegmental area and raphe nuclei. Finally, by means of algebraic criteria for synchronizability of the neurocircuitry, the suitability for in silico modeling of acute and chronic drug effects is indicated. Indeed, we introduced as an example a dynamical system for modeling the effects of acute ethanol administration in rats and obtained an increase in dopamine release in the nucleus accumbens-a hallmark of drug reinforcement-to an extent similar to that seen in numerous microdialysis studies. We conclude that the present neurocircuitry provides a structural and dynamical framework for large-scale mathematical models and will help to predict chronic drug effects on brain function.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neurocircuitry for modeling drug effects

2012

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“…Basal ganglia (BG) dysfunction has been implicated in the motor signs of Parkinson’s disease (PD) in humans (Brown et al, 2001; Doyle et al, 2005; Dejean et al, 2008), animal models (Burkhardt et al, 2007; Cruz et al, 2009) and computational studies (Berns and Sejnowski, 1998; Frank, 2006; Humphries et al, 2006; Kang and Lowery, 2009; Noori and Jager, 2010). The pathoetiology of the disease is attributed to dopaminergic (DA) denervation of BG due to neuronal loss within the substantia nigra.…”

Section: Introductionmentioning

confidence: 99%

200–300Hz movement modulated oscillations in the internal globus pallidus of patients with Parkinson's Disease

Tsiokos¹,

Xiao²,

Pouratian³

2013

Neurobiology of Disease

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Symptoms in Parkinson’s disease (PD) have been linked to oscillatory activity within the basal ganglia. In humans, such activity has been detected mainly in the local field potentials (LFPs) recorded from electrode contacts used for deep brain stimulation. Although most studies have focused on activity within the subthalamic nucleus (STN), the internal part of the globus pallidus (GPi) is considered an equally efficacious site for therapeutic neuromodulation. Moreover, while most investigations have evaluated changes in oscillatory activity in the beta (12–35 Hz) and gamma (35–100 Hz) bands, our preliminary spectral analysis of LFP signals in the GPi suggested distinct activity at higher frequencies as well. We hypothesized there is a unique LFP signature in the GPi that consists of movement modulated spectral power increases above 100Hz. Using invasive recordings from the GPi of patients undergoing DBS, in addition to confirming increased beta band activity within the GPi of patients with PD, we have identified and characterized a previously undescribed peak between 200–300 Hz centered at approximately 235 Hz, whose height and width but not center frequency are movement modulated. An increase in peak height is not transient, but rather persists for the duration of movement. The 200–300 Hz rhythms in the GPi could have a functional role in the basal ganglia reentrant circuits by encoding output information entering the thalamo-cortical network or by organizing downstream activity for the successful execution of tasks.

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“…An overview, with special regard on schizophrenia, is given by Rolls et al [35] . However, for the examination of psychiatric disorders, the focus is mostly laid on the imbalance of diff erent transmitter systems [38] , partly with large scale modelling approaches [27] but mostly with detailed simulations of transmitter metabolism and homeostasis [34] . The question is, how the diverse modelling approaches can be connected towards a better understanding of psychiatric disorders which requires to understand the underlying disturbances of brain functions on the basis of cellular processes.…”

Section: Introduction ▼mentioning

confidence: 99%

Neurones and Synapses for Systemic Models of Psychiatric Disorders

Postnova

Rosa

2010

Pharmacopsychiatry

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We propose a mechanism-based modelling approach which brings together the most relevant features of neural dynamics and synaptic transmission for clinically valuable simulations of psychiatric disorders and their pharmaceutical treatment. It is based on a minimal, but physiologically justified concept, which allows to account for a great diversity of neuronal dynamics and synaptic mechanisms. It can simulate ionotropic as well as metabotropic receptors in addition to the effects of eventual co-transmitters and external neuromodulators. The proposed model can mimic the clinically most important aspects of synaptic disturbances, such as impaired transmitter availability or reduced number of postsynaptic receptors, for example due to their internalization as a function of transmitter concentration. It also allows evaluation of the effects of drugs with specific actions such as receptor agonists and antagonists or reuptake inhibitors. It is a major advantage of this physiologically based approach that it can be adjusted to different types of neurons and synapses, and also can be extended to more elaborate physiological situations, e. g. by including additional receptors or ion channels, whenever this is indicated by clinical or experimental data.

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Neurochemical Oscillations in the Basal Ganglia

Cited by 10 publications

References 56 publications

Neurocircuitry for modeling drug effects

Neurocircuitry for modeling drug effects

200–300Hz movement modulated oscillations in the internal globus pallidus of patients with Parkinson's Disease

Neurones and Synapses for Systemic Models of Psychiatric Disorders

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