Mouse subthalamic nucleus neurons with local axon collaterals

Gouty‐Colomer, Laurie‐Anne; François, Michel; Baude, Agnès; Lopez-Pauchet, Catherine; Dufour, Amandine; Cossart, Rosa; Hammond, Constance

doi:10.1002/cne.24334

Cited by 13 publications

(17 citation statements)

References 31 publications

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“…This is probably because excitability is decreased after injection, and disinhibition from the GPe could not effectively increase neuronal firing in the STN. Glutamatergic local axon collaterals of STN neurons may also amplify late excitation (Fujimoto and Kita, 1993;Gouty-Colomer et al, 2018).…”

Section: Origin Of Late Excitationmentioning

confidence: 99%

Cortical Control of Subthalamic Neuronal Activity through the Hyperdirect and Indirect Pathways in Monkeys

et al. 2020

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The subthalamic nucleus (STN) plays a key role in the control of voluntary movements and basal ganglia disorders, such as Parkinson's disease and hemiballismus. The STN receives glutamatergic inputs directly from the cerebral cortex via the cortico-STN hyperdirect pathway and GABAergic inputs from the external segment of the globus pallidus (GPe) via the corticostriato-GPe-STN indirect pathway. The STN then drives the internal segment of the globus pallidus, which is the output nucleus of the basal ganglia. Thus, clarifying how STN neuronal activity is controlled by the two inputs is crucial. Cortical stimulation evokes early excitation and late excitation in STN neurons, intervened by a short gap. Here, to examine the origin of each component of this biphasic response, we recorded neuronal activity in the STN, combined with electrical stimulation of the motor cortices and local drug application in two male monkeys (Macaca fuscata) in the awake state. Local application of glutamate receptor antagonists, a mixture of an AMPA/kainate receptor antagonist and an NMDA receptor antagonist, into the vicinity of recorded STN neurons specifically diminished early excitation. Blockade of the striatum (putamen) or GPe with local injection of a GABA A receptor agonist, muscimol, diminished late excitation in the STN. Blockade of striato-GPe transmission with local injection of a GABA A receptor antagonist, gabazine, into the GPe also abolished late excitation. These results indicate that cortically evoked early and late excitation in the STN is mediated by the cortico-STN glutamatergic hyperdirect and the cortico-striato-GPe-STN indirect pathways, respectively.

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Section: Origin Of Late Excitationmentioning

confidence: 99%

Cortical Control of Subthalamic Neuronal Activity through the Hyperdirect and Indirect Pathways in Monkeys

et al. 2020

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“…The STN is the main provider of excitatory inputs to the SNr, and the properties of STN-SNr synapses have been well characterized. Electrical stimulation of STN axons triggers monosynaptic EPSCs [195,196], while the same type of stimulation delivered in the STN itself gives rise to complex EPSCs [197,198], which are believed to be generated by the activation of STN local axon collaterals [197,199]. Both D1Rs and D2Rs are present on STN-SNr synaptic terminals and activation of D1Rs enhances while activation of D2Rs decreases STN-SNr EPSC amplitude [196].…”

Section: The Substantia Nigra Pars Reticulatamentioning

confidence: 99%

Cellular and Synaptic Dysfunctions in Parkinson’s Disease: Stepping Out of the Striatum

Mallet

Delgado

Chazalon

et al. 2019

Cells

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The basal ganglia (BG) are a collection of interconnected subcortical nuclei that participate in a great variety of functions, ranging from motor programming and execution to procedural learning, cognition, and emotions. This network is also the region primarily affected by the degeneration of midbrain dopaminergic neurons localized in the substantia nigra pars compacta (SNc). This degeneration causes cellular and synaptic dysfunctions in the BG network, which are responsible for the appearance of the motor symptoms of Parkinson’s disease. Dopamine (DA) modulation and the consequences of its loss on the striatal microcircuit have been extensively studied, and because of the discrete nature of DA innervation of other BG nuclei, its action outside the striatum has been considered negligible. However, there is a growing body of evidence supporting functional extrastriatal DA modulation of both cellular excitability and synaptic transmission. In this review, the functional relevance of DA modulation outside the striatum in both normal and pathological conditions will be discussed.

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“…More specifically, incoming fibers of both indirect (Baufreton et al, 2009) and hyperdirect pathways collateralize in the STN (Kita and Kita, 2012), and their divergence may serve as an anatomical prerequisite for synchronous recruitment. Mutual synaptic connectivity between STN neurons has been suggested on the basis of anatomical (Hammond and Yelnik, 1983;Kita et al, 1983;Chang et al, 1984;Ammari et al, 2010;Gouty-Colomer et al, 2018) and indirect electrophysiological observations (Shen and Johnson, 2006;Ammari et al, 2010;Chu et al, 2012), but these observations were called into question by contrasting findings (Wilson et al, 2004;Koshimizu et al, 2013). Thus, the mere existence of functional intranuclear connections remains contentious.…”

Section: Significance Statementmentioning

confidence: 99%

“…As the possibility of intranuclear synaptic contacts has been raised by previous anatomical studies (Hammond and Yelnik, 1983;Kita et al, 1983;Chang et al, 1984;Ammari et al, 2010;Gouty-Colomer et al, 2018), we examined the overlap of dendritic and axonal arborizations of the recorded neurons. Visual inspection revealed axo-dendritic proximities between neuron pairs of the recorded and visualized STN clusters (Fig.…”

Section: Multipatch Experiments Reveal No Synaptic Interconnectivity mentioning

confidence: 99%

Connectivity and dynamics underlying synaptic control of the Subthalamic Nucleus

et al. 2019

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Adaptive motor control critically depends on the interconnected nuclei of the basal ganglia in the CNS. A pivotal element of the basal ganglia is the subthalamic nucleus (STN), which serves as a therapeutic target for deep brain stimulation (DBS) in movement disorders, such as Parkinson's disease. The functional connectivity of the STN at the microcircuit level, however, still requires rigorous investigation. Here we combine multiple simultaneous whole-cell recordings with extracellular stimulation and post hoc neuroanatomical analysis to investigate intrinsic and afferent connectivity and synaptic properties of the STN in acute brain slices obtained from rats of both sexes. Our data reveal an absence of intrinsic connectivity and an afferent innervation with low divergence, suggesting that STN neurons operate as independent processing elements driven by upstream structures. Hence, synchrony in the STN, a hallmark of motor processing, exclusively depends on the interactions and dynamics of GABAergic and glutamatergic afferents. Importantly, these inputs are subject to differential short-term depression when stimulated at high, DBS-like frequencies, shifting the balance of excitation and inhibition toward inhibition. Thus, we present a mechanism for fast yet transient decoupling of the STN from synchronizing afferent control. Together, our study provides new insights into the microcircuit organization of the STN by identifying its neurons as parallel processing units and thus sets new constraints for future computational models of the basal ganglia. The observed differential short-term plasticity of afferent inputs further offers a basis to better understand and optimize DBS algorithms.

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Mouse subthalamic nucleus neurons with local axon collaterals

Cited by 13 publications

References 31 publications

Cortical Control of Subthalamic Neuronal Activity through the Hyperdirect and Indirect Pathways in Monkeys

Cortical Control of Subthalamic Neuronal Activity through the Hyperdirect and Indirect Pathways in Monkeys

Cellular and Synaptic Dysfunctions in Parkinson’s Disease: Stepping Out of the Striatum

Connectivity and dynamics underlying synaptic control of the Subthalamic Nucleus

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