A biologically constrained model of the whole basal ganglia addressing the paradoxes of connections and selection

Liénard, Jean‐Sylvain; Girard, Benoît

doi:10.1007/s10827-013-0476-2

Cited by 29 publications

(88 citation statements)

References 111 publications

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“…Another—sporting a highly sophisticated anatomical and physiological specification—allots the short indirect pathway connection from GPe to GPi a diffuse organisation (i.e. a one-to-many communication across channels), essentially replacing the hyperdirect pathway as a source of restraint, the latter being locked to baseline levels of activity (Lienard and Girard 2014). A final variation (Brown et al 2004) notes that the cortical input to the STN is formed exclusively by collaterals of executive cells in layer 5B (and not by ‘planning’ corticostriatal cells in other layers)3, and from that perspective is not suited to a role as the initial source of restraint.…”

Section: Founding Conceptions Of the Cortico-bg Loopmentioning

confidence: 99%

The functional logic of corticostriatal connections

Shipp

2016

Brain Struct Funct

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Unidirectional connections from the cortex to the matrix of the corpus striatum initiate the cortico-basal ganglia (BG)-thalamocortical loop, thought to be important in momentary action selection and in longer-term fine tuning of behavioural repertoire; a discrete set of striatal compartments, striosomes, has the complementary role of registering or anticipating reward that shapes corticostriatal plasticity. Re-entrant signals traversing the cortico-BG loop impact predominantly frontal cortices, conveyed through topographically ordered output channels; by contrast, striatal input signals originate from a far broader span of cortex, and are far more divergent in their termination. The term ‘disclosed loop’ is introduced to describe this organisation: a closed circuit that is open to outside influence at the initial stage of cortical input. The closed circuit component of corticostriatal afferents is newly dubbed ‘operative’, as it is proposed to establish the bid for action selection on the part of an incipient cortical action plan; the broader set of converging corticostriatal afferents is described as contextual. A corollary of this proposal is that every unit of the striatal volume, including the long, C-shaped tail of the caudate nucleus, should receive a mandatory component of operative input, and hence include at least one area of BG-recipient cortex amongst the sources of its corticostriatal afferents. Individual operative afferents contact twin classes of GABAergic striatal projection neuron (SPN), distinguished by their neurochemical character, and onward circuitry. This is the basis of the classic direct and indirect pathway model of the cortico-BG loop. Each pathway utilises a serial chain of inhibition, with two such links, or three, providing positive and negative feedback, respectively. Operative co-activation of direct and indirect SPNs is, therefore, pictured to simultaneously promote action, and to restrain it. The balance of this rival activity is determined by the contextual inputs, which summarise the external and internal sensory environment, and the state of ongoing behavioural priorities. Notably, the distributed sources of contextual convergence upon a striatal locus mirror the transcortical network harnessed by the origin of the operative input to that locus, thereby capturing a similar set of contingencies relevant to determining action. The disclosed loop formulation of corticostriatal and subsequent BG loop circuitry, as advanced here, refines the operating rationale of the classic model and allows the integration of more recent anatomical and physiological data, some of which can appear at variance with the classic model. Equally, it provides a lucid functional context for continuing cellular studies of SPN biophysics and mechanisms of synaptic plasticity.

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Section: Founding Conceptions Of the Cortico-bg Loopmentioning

confidence: 99%

The functional logic of corticostriatal connections

Shipp

2016

Brain Struct Funct

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“…; Leblois et al . ; Liénard & Girard, ). However, these models fail to capture much of the diversity of experimental data concerning phasic responses and oscillatory properties of healthy BG.…”

Section: Introductionmentioning

confidence: 99%

Frequency and function in the basal ganglia: the origins of beta and gamma band activity

Blenkinsop

Anderson

Gurney

2017

The Journal of Physiology

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Neural oscillations in the basal ganglia (BG) are well studied yet remain poorly understood. Behavioural correlates of spectral activity are well described, yet a quantitative hypothesis linking time domain dynamics and spectral properties to BG function has been lacking. We show, for the first time, that a unified description is possible by interpreting previously ignored structure in data describing globus pallidus interna responses to cortical stimulation. These data were used to expose a pair of distinctive neuronal responses to the stimulation. This observation formed the basis for a new mathematical model of the BG, quantitatively fitted to the data, which describes the dynamics in the data, and is validated against other stimulus protocol experiments. A key new result is that when the model is run using inputs hypothesised to occur during the performance of a motor task, beta and gamma frequency oscillations emerge naturally during static-force and movement, respectively, consistent with experimental local field potentials. This new model predicts that the pallido-striatum connection has a key role in the generation of beta band activity, and that the gamma band activity associated with motor task performance has its origins in the pallido-subthalamic feedback loop. The network's functionality as a selection mechanism also occurs as an emergent property, and closer fits to the data gave better selection properties. The model provides a coherent framework for the study of spectral, temporal and functional analyses of the BG and therefore lays the foundation for an integrated approach to study BG pathologies such as Parkinson's disease in silico.

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“…This paper by Nevado‐Holgado et al . (), alongside recent investigations by Liénard & Girard () into the function of the basal ganglia, provide elegant demonstrations of the power of using constrained searches through huge numbers of models to generate unique insights into a neural system.…”

Section: Connectivity Of Subthalamic Nucleus–globus Pallidus Network mentioning

confidence: 92%

“…What is the effective connectivity in the healthy network? How does the loss of dopamine act to change the effective connectivity of the STN-GP network?This paper by Nevado-Holgado et al (2014), alongside recent investigations by Liénard & Girard (2014) into the function of the basal ganglia, provide elegant demonstrations of the power of using constrained searches through huge numbers of models to generate unique insights into a neural system.…”

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confidence: 95%

Slaves to the rhythm: coupling of the subthalamic nucleus–globus pallidus network in Parkinsonian oscillations

Humphries

2014

The Journal of Physiology

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Systems neuroscience approaches to the study of Parkinson's disease seek to understand how the chronic loss of dopamine alters the normal operation of neuronal networks, resulting in the cardinal symptoms (tremor, rigidity, akinesia and bradykinesia). A recurring theme is the combined change in synchronization and oscillation of whole populations of neurons. Both Parkinsonian patients and animal models show enhanced synchrony of firing between neurons within the cortex and the nuclei of the basal ganglia, correlated with a markedly increased oscillation of activity in the beta band (13-30 Hz;Hammond et al. 2007). With mounting evidence that this enhanced beta oscillation is pathological, the priority is to locate its source mechanism(s). Doing so would suggest a locus for targeted chemical, electrical and other interventions for treating Parkinson's disease. A particular focus has been the recurrent connections between the subthalamic nucleus (STN) and globus pallidus (GP) of the basal ganglia. In animal models of Parkinson's disease, both structures show changed firing patterns and increased neural synchrony, corresponding to enhanced beta-band oscillations. As the STN and GP form a negative feedback loop, a classical system for generating oscillations in engineering, many have proposed that this loop is the source of pathological changes in oscillation and synchrony.If only it were that simple. Evidence against this attractively simple hypothesis has come from a recent study showing that GP comprises two populations functionally defined by their phase of correlation with global oscillations in the cortex under general anaesthesia (Mallet et al. 2008). These authors reported a population labelled GP-TA that fire during activation of the cortical electrocorticogram, thus in phase with STN, and a population labelled GP-TI that fire during inactivation of the cortical electrocorticogram, thus out of phase with STN and GP-TA. These data have thrown open the question of how the STN and GP connections are organized and thus raised the broader question, on what should we base our theories of neural dynamics in the Parkinsonian brain?In this issue of The Journal of Physiology, Nevado-Holgado et al. (2014) use computational models to tackle this problem, with the aim of determining the effective connectivity between STN and GP populations in the Parkinsonian brain. They used a dynamic model describing the change of firing rates in the STN, GP-TI and GP-TA populations, driven by oscillatory inputs from cortex, thalamus and striatum (Fig. 1). While many parameters could be fixed from experimental data, the remaining free parameters of the model encode the many unknowns about this system, particularly the effective weights of connections between each population and of the inputs. To solve this problem, Nevado-Holgado et al. (2014) epitomized the modern use of computer power to search the high-dimensional space of possible parameter values and possible models, with the goal of fitting the response of each population to expe...

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A biologically constrained model of the whole basal ganglia addressing the paradoxes of connections and selection

Cited by 29 publications

References 111 publications

The functional logic of corticostriatal connections

The functional logic of corticostriatal connections

Frequency and function in the basal ganglia: the origins of beta and gamma band activity

Slaves to the rhythm: coupling of the subthalamic nucleus–globus pallidus network in Parkinsonian oscillations

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