Circuits that contain the Neurotransmitter : Dopamine

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    Models   Description
1. A 1000 cell network model for Lateral Amygdala (Kim et al. 2013)
1000 Cell Lateral Amygdala model for investigation of plasticity and memory storage during Pavlovian Conditioning.
2. A basal ganglia model of aberrant learning (Ursino et al. 2018)
A comprehensive, biologically inspired neurocomputational model of action selection in the Basal Ganglia allows simulation of dopamine induced aberrant learning in Parkinsonian subjects. In particular, the model simulates the Alternate Finger Tapping motor task as an indicator of bradykinesia.
3. A contracting model of the basal ganglia (Girard et al. 2008)
Basal ganglia model : selection processes between channels, dynamics controlled by contraction analysis, rate-coding model of neurons based on locally projected dynamical systems (lPDS).
4. A neural model of Parkinson`s disease (Cutsuridis and Perantonis 2006, Cutsuridis 2006, 2007)
"A neural model of neuromodulatory (dopamine) control of arm movements in Parkinson’s disease (PD) bradykinesia was recently introduced [1, 2]. The model is multi-modular consisting of a basal ganglia module capable of selecting the most appropriate motor command in a given context, a cortical module for coordinating and executing the final motor commands, and a spino-musculo-skeletal module for guiding the arm to its final target and providing proprioceptive (feedback) input of the current state of the muscle and arm to higher cortical and lower spinal centers. ... The new (extended) model [3] predicted that the reduced reciprocal disynaptic Ia inhibition in the DA depleted case doesn’t lead to the co-contraction of antagonist motor units." See below readme and papers for more and details.
5. Acetylcholine-modulated plasticity in reward-driven navigation (Zannone et al 2018)
"Neuromodulation plays a fundamental role in the acquisition of new behaviours. In previous experimental work, we showed that acetylcholine biases hippocampal synaptic plasticity towards depression, and the subsequent application of dopamine can retroactively convert depression into potentiation. We also demonstrated that incorporating this sequentially neuromodulated Spike- Timing-Dependent Plasticity (STDP) rule in a network model of navigation yields effective learning of changing reward locations. Here, we employ computational modelling to further characterize the effects of cholinergic depression on behaviour. We find that acetylcholine, by allowing learning from negative outcomes, enhances exploration over the action space. We show that this results in a variety of effects, depending on the structure of the model, the environment and the task. Interestingly, sequentially neuromodulated STDP also yields flexible learning, surpassing the performance of other reward-modulated plasticity rules."
6. Basal Ganglia and Levodopa Pharmacodynamics model for parameter estimation in PD (Ursino et al 2020)
Parkinson disease (PD) is characterized by a clear beneficial motor response to levodopa (LD) treatment. However, with disease progression and longer LD exposure, drug-related motor fluctuations usually occur. Recognition of the individual relationship between LD concentration and its effect may be difficult, due to the complexity and variability of the mechanisms involved. This work proposes an innovative procedure for the automatic estimation of LD pharmacokinetics and pharmacodynamics parameters, by a biologically-inspired mathematical model. An original issue, compared with previous similar studies, is that the model comprises not only a compartmental description of LD pharmacokinetics in plasma and its effect on the striatal neurons, but also a neurocomputational model of basal ganglia action selection. Parameter estimation was achieved on 26 patients (13 with stable and 13 with fluctuating LD response) to mimic plasma LD concentration and alternate finger tapping frequency along four hours after LD administration, automatically minimizing a cost function of the difference between simulated and clinical data points. Results show that individual data can be satisfactorily simulated in all patients and that significant differences exist in the estimated parameters between the two groups. Specifically, the drug removal rate from the effect compartment, and the Hill coefficient of the concentration-effect relationship were significantly higher in the fluctuating than in the stable group. The model, with individualized parameters, may be used to reach a deeper comprehension of the PD mechanisms, mimic the effect of medication, and, based on the predicted neural responses, plan the correct management and design innovative therapeutic procedures.
7. Basal ganglia network model of subthalamic deep brain stimulation (Hahn and McIntyre 2010)
Basal ganglia network model of parkinsonian activity and subthalamic deep brain stimulation in non-human primates from the article Instructions are provided in the README.txt file. Contact hahnp@ccf.org if you have any questions about the implementation of the model. Please include "ModelDB - BGnet" in the subject heading.
8. Basal ganglia-thalamocortical loop model of action selection (Humphries and Gurney 2002)
We embed our basal ganglia model into a wider circuit containing the motor thalamocortical loop and thalamic reticular nucleus (TRN). Simulation of this extended model showed that the additions gave five main results which are desirable in a selection/switching mechanism. First, low salience actions (i.e. those with low urgency) could be selected. Second, the range of salience values over which actions could be switched between was increased. Third, the contrast between the selected and non-selected actions was enhanced via improved differentiation of outputs from the BG. Fourth, transient increases in the salience of a non-selected action were prevented from interrupting the ongoing action, unless the transient was of sufficient magnitude. Finally, the selection of the ongoing action persisted when a new closely matched salience action became active. The first result was facilitated by the thalamocortical loop; the rest were dependent on the presence of the TRN. Thus, we conclude that the results are consistent with these structures having clearly defined functions in action selection.
9. Cognitive and motor cortico-basal ganglia interactions during decision making (Guthrie et al 2013)
This is a re-implementation of Guthrie et al 2013 by Topalidou and Rougier 2015. The original study investigated how multiple level action selection could be performed by the basal ganglia.
10. Dynamic dopamine modulation in the basal ganglia: Learning in Parkinson (Frank et al 2004,2005)
See README file for all info on how to run models under different tasks and simulated Parkinson's and medication conditions.
11. Excitotoxic loss of dopaminergic cells in PD (Muddapu et al 2019)
"... A couple of the proposed mechanisms, however, show potential for the development of a novel line of PD (Parkinson's disease) therapeutics. One of these mechanisms is the peculiar metabolic vulnerability of SNc (Substantia Nigra pars compacta) cells compared to other dopaminergic clusters; the other is the SubThalamic Nucleus (STN)-induced excitotoxicity in SNc. To investigate the latter hypothesis computationally, we developed a spiking neuron network-model of SNc-STN-GPe system. In the model, prolonged stimulation of SNc cells by an overactive STN leads to an increase in ‘stress’ variable; when the stress in a SNc neuron exceeds a stress threshold, the neuron dies. The model shows that the interaction between SNc and STN involves a positive-feedback due to which, an initial loss of SNc cells that crosses a threshold causes a runaway-effect, leading to an inexorable loss of SNc cells, strongly resembling the process of neurodegeneration. The model further suggests a link between the two aforementioned mechanisms of SNc cell loss. Our simulation results show that the excitotoxic cause of SNc cell loss might initiate by weak-excitotoxicity mediated by energy deficit, followed by strong-excitotoxicity, mediated by a disinhibited STN. A variety of conventional therapies were simulated to test their efficacy in slowing down SNc cell loss. Among them, glutamate inhibition, dopamine restoration, subthalamotomy and deep brain stimulation showed superior neuroprotective-effects in the proposed model."
12. Gamma genesis in the basolateral amygdala (Feng et al 2019)
Using in vitro and in vivo data we develop the first large-scale biophysically and anatomically realistic model of the basolateral amygdala nucleus (BL), which reproduces the dynamics of the in vivo local field potential (LFP). Significantly, it predicts that BL intrinsically generates the transient gamma oscillations observed in vivo. The model permitted exploration of the poorly understood synaptic mechanisms underlying gamma genesis in BL, and the model's ability to compute LFPs at arbitrary numbers of recording sites provided insights into the characteristics of the spatial properties of gamma bursts. Furthermore, we show how gamma synchronizes principal cells to overcome their low firing rates while simultaneously promoting competition, potentially impacting their afferent selectivity and efferent drive, and thus emotional behavior.
13. Modeling the effects of dopamine on network synchronization (Komek et al. 2012)
Dopamine modulates cortical circuit activity in part through its actions on GABAergic interneurons, including increasing the excitability of fast-spiking interneurons. Though such effects have been demonstrated in single cells, there are no studies that examine how such mechanisms may lead to the effects of dopamine at a neural network level. In this study, we investigated the effects of dopamine on synchronization in two simulated neural networks; one biophysical model composed of Wang-Buzsaki neurons and a reduced model with theta neurons. In both models, we show that parametrically varying the levels of dopamine, modeled through the changes in the excitability of interneurons, reveals an inverted-U shaped relationship, with low gamma band power at both low and high dopamine levels and optimal synchronization at intermediate levels. Moreover, such a relationship holds when the external input is both tonic and periodic at gamma band range. Together, our results indicate that dopamine can modulate cortical gamma band synchrony in an inverted-U fashion and that the physiologic effects of dopamine on single fast-spiking interneurons can give rise to such non-monotonic effects at the network level.
14. Multiscale model of excitotoxicity in PD (Muddapu and Chakravarthy 2020)
Parkinson's disease (PD) is a neurodegenerative disorder caused by loss of dopaminergic neurons in Substantia Nigra pars compacta (SNc). Although the exact cause of cell death is not clear, the hypothesis that metabolic deficiency is a key factor has been gaining attention in recent years. In the present study, we investigate this hypothesis using a multi-scale computational model of the subsystem of the basal ganglia comprising Subthalamic Nucleus (STN), Globus Pallidus externa (GPe) and SNc. The proposed model is a multiscale model in that interactions among the three nuclei are simulated using more abstract Izhikevich neuron models, while the molecular pathways involved in cell death of SNc neurons are simulated in terms of detailed chemical kinetics. Simulation results obtained from the proposed model showed that energy deficiencies occurring at cellular and network levels could precipitate the excitotoxic loss of SNc neurons in PD. At the subcellular level, the models show how calcium elevation leads to apoptosis of SNc neurons. The therapeutic effects of several neuroprotective interventions are also simulated in the model. From neuroprotective studies, it was clear that glutamate inhibition and apoptotic signal blocker therapies were able to halt the progression of SNc cell loss when compared to other therapeutic interventions, which only slows down the progression of SNc cell loss.
15. Population-level model of the basal ganglia and action selection (Gurney et al 2001, 2004)
We proposed a new functional architecture for the basal ganglia (BG) based on the premise that these brain structures play a central role in behavioural action selection. The papers quantitatively describes the properties of the model using analysis and simulation. In the first paper, we show that the decomposition of the BG into selection and control pathways is supported in several ways. First, several elegant features are exposed--capacity scaling, enhanced selectivity and synergistic dopamine modulation--which might be expected to exist in a well designed action selection mechanism. Second, good matches between model GPe output and GPi and SNr output, and neurophysiological data, have been found. Third, the behaviour of the model as a signal selection mechanism has parallels with some kinds of action selection observed in animals under various levels of dopaminergic modulation. In the second paper, we extend the BG model to include new connections, and show that action selection is maintained. In addition, we provide quantitative measures for defining different forms of selection, and methods for assessing performance changes in computational neuroscience models.
16. Reinforcement learning of targeted movement (Chadderdon et al. 2012)
"Sensorimotor control has traditionally been considered from a control theory perspective, without relation to neurobiology. In contrast, here we utilized a spiking-neuron model of motor cortex and trained it to perform a simple movement task, which consisted of rotating a single-joint “forearm” to a target. Learning was based on a reinforcement mechanism analogous to that of the dopamine system. This provided a global reward or punishment signal in response to decreasing or increasing distance from hand to target, respectively. Output was partially driven by Poisson motor babbling, creating stochastic movements that could then be shaped by learning. The virtual forearm consisted of a single segment rotated around an elbow joint, controlled by flexor and extensor muscles. ..."
17. Roles of subthalamic nucleus and DBS in reinforcement conflict-based decision making (Frank 2006)
Deep brain stimulation (DBS) of the subthalamic nucleus dramatically improves the motor symptoms of Parkinson's disease, but causes cognitive side effects such as impulsivity. This model from Frank (2006) simulates the role of the subthalamic nucleus (STN) within the basal ganglia circuitry in decision making. The STN dynamically modulates network decision thresholds in proportion to decision conflict. The STN ``hold your horses'' signal adaptively allows the system more time to settle on the best choice when multiple options are valid. The model also replicates effects in Parkinson's patients on and off DBS in experiments designed to test the model (Frank et al, 2007).
18. Spiking neuron model of the basal ganglia (Humphries et al 2006)
A spiking neuron model of the basal ganglia (BG) circuit (striatum, STN, GP, SNr). Includes: parallel anatomical channels; tonic dopamine; dopamine receptors in striatum, STN, and GP; burst-firing in STN; GABAa, AMPA, and NMDA currents; effects of synaptic location. Model demonstrates selection and switching of input signals. Replicates experimental data on changes in slow-wave (<1 Hz) and gamma-band oscillations within BG nuclei following lesions and pharmacological manipulations.
19. Striatal dopamine ramping: an explanation by reinforcement learning with decay (Morita & Kato, 2014)
Incorporation of decay of learned values into temporal-difference (TD) learning (Sutton & Barto, 1998, Reinforcement Learning (MIT Press)) causes ramping of TD reward prediction error (RPE), which could explain, given the hypothesis that dopamine represents TD RPE (Montague et al., 1996, J Neurosci 16:1936; Schultz et al., 1997, Science 275:1593), the reported ramping of the dopamine concentration in the striatum in a reward-associated spatial navigation task (Howe et al., 2013, Nature 500:575).
20. Striatal GABAergic microcircuit, dopamine-modulated cell assemblies (Humphries et al. 2009)
To begin identifying potential dynamically-defined computational elements within the striatum, we constructed a new three-dimensional model of the striatal microcircuit's connectivity, and instantiated this with our dopamine-modulated neuron models of the MSNs and FSIs. A new model of gap junctions between the FSIs was introduced and tuned to experimental data. We introduced a novel multiple spike-train analysis method, and apply this to the outputs of the model to find groups of synchronised neurons at multiple time-scales. We found that, with realistic in vivo background input, small assemblies of synchronised MSNs spontaneously appeared, consistent with experimental observations, and that the number of assemblies and the time-scale of synchronisation was strongly dependent on the simulated concentration of dopamine. We also showed that feed-forward inhibition from the FSIs counter-intuitively increases the firing rate of the MSNs.
21. Striatal GABAergic microcircuit, spatial scales of dynamics (Humphries et al, 2010)
The main thrust of this paper was the development of the 3D anatomical network of the striatum's GABAergic microcircuit. We grew dendrite and axon models for the MSNs and FSIs and extracted probabilities for the presence of these neurites as a function of distance from the soma. From these, we found the probabilities of intersection between the neurites of two neurons given their inter-somatic distance, and used these to construct three-dimensional striatal networks. These networks were examined for their predictions for the distributions of the numbers and distances of connections for all the connections in the microcircuit. We then combined the neuron models from a previous model (Humphries et al, 2009; ModelDB ID: 128874) with the new anatomical model. We used this new complete striatal model to examine the impact of the anatomical network on the firing properties of the MSN and FSI populations, and to study the influence of all the inputs to one MSN within the network.
22. Synchronization by D4 dopamine receptor-mediated phospholipid methylation (Kuznetsova, Deth 2008)
"We describe a new molecular mechanism of dopamine-induced membrane protein modulation that can tune neuronal oscillation frequency to attention related gamma rhythm. This mechanism is based on the unique ability of D4 dopamine receptors (D4R) to carry out phospholipid methylation (PLM) that may affect the kinetics of ion channels. We show that by deceasing the inertia of the delayed rectifier potassium channel, a transition to 40 Hz oscillations can be achieved. ..."

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