The Basal Ganglia

Dudman, Joshua T.; Gerfen, Charles R.

doi:10.1016/b978-0-12-374245-2.00017-6

Cited by 48 publications

(58 citation statements)

References 268 publications

(442 reference statements)

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“…Briefly, we implemented a model of basal ganglia as a parallel circuit that receives copies of motor commands as input to striatum. We simplified the internal connectivity of basal ganglia (Dudman and Gerfen, 2015) such that the indirect pathway produced a spatially broad and temporally delayed excitatory input to the SNr network similar to previous models (Humphries et al, 2006). The SNr output downstream from direct pathway input was integrated at 'premotor' structures with motor commands directly from cortex to produce a predicted, net motor output (Yttri and Dudman, 2016).…”

Section: Figurementioning

confidence: 99%

“…The canonical basal ganglia circuit is composed of nuclei that project, in largely feed-forward fashion, from input nuclei, striatum and subthalamic nucleus (STN), to output nuclei, substantia nigra pars reticulata (SNr) and internal globus pallidus (GPi) (Dudman and Gerfen, 2015). From input to output, the number of projection neurons decreases dramatically from a few million in the striatum to roughly thirty thousand in the SNr (Oorschot, 1996).…”

Section: Introductionmentioning

confidence: 99%

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Behavioral evidence for feedback gain control by the inhibitory microcircuit of the substantia nigra

Brown

Martin

Dudman

2016

Preprint

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We recently demonstrated that the collaterals of substantia nigra (SN) projection neurons can implement divisive feedback inhibition, or gain control . While in vivo recordings were consistent with divisive feedback inhibition, a causal test was lacking. A gain control model of the nigral microcircuit implies behavioral effects of disrupting intranigral inhibition that are distinct from previous functional models. To test the model predictions experimentally, we develop a chemogenetic approach that can selectively suppress synaptic release within the substantial nigra without affecting the propagation of activity to extranigral targets. We observe behavioral consequences of suppressing intranigral inhibition that are uniquely consistent with a gain control model. Our data further suggest that if endogenous metabotropic signaling can modulate intranigral synapses, this would provide a circuit mechanism for an exploitation/exploration trade-off in which the timing and variability of goaldirected movements are controlled independently of changes in action.

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Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Behavioral evidence for feedback gain control by the inhibitory microcircuit of the substantia nigra

Brown

Martin

Dudman

2016

Preprint

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“…The striatum is ideal because mCH patterns are highly cell-specific and the vast majority of neurons (95%) in this region are inhibitory medium spiny neurons (48,49). We found that methylation was stable in the absence of MeCP2 (Figure 2B, Supplemental Figure 3), but the Dnmt3a conditional knockout lost ~90% of mCH ( Figure 2C).…”

Section: Mecp2 Is a Partial Reader Of Dnmt3a Dependent Methylation Inmentioning

confidence: 86%

Loss of Dnmt3a dependent methylation in inhibitory neurons impairs neural function through a mechanism that impacts Rett syndrome

Lavery

Ure

Wan

et al. 2019

Preprint

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Methylated cytosine is an effector of epigenetic gene regulation. In the mammalian brain, the DNA methyltransferase, Dnmt3a, is the sole "writer" of atypical non-CpG methylation (mCH), and methyl CpG binding protein 2 (MeCP2) is the only known "reader" for mCH. We set out to determine if MeCP2 is the sole reader for Dnmt3a dependent methylation by comparing mice lacking either Dnmt3a or MeCP2 in GABAergic inhibitory neurons. Loss of either the writer or the reader causes overlapping and distinct features from the behavioral to the molecular level. Loss of Dnmt3a results in global loss of mCH and a small subset of mCG sites resulting in more widespread transcriptional alterations and severe neurological dysfunction than seen upon MeCP2 loss. These data indicate that MeCP2 is responsible for reading part of the Dnmt3a dependent methylation in the brain. Importantly, the impact of MeCP2 on genes differentially expressed in both cKO models shows a strong dependence on mCH, but not Dnmt3a dependent mCG, consistent with mCH playing a central role in the pathogenesis of Rett Syndrome.

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“…Glutamatergic projections arise from most cortical regions, as well as thalamic and limbic regions. Cortical inputs descend in a topographic fashion with neighboring regions of cortex projecting to adjacent regions of the striatum (Bolam et al, 2000; Dudman and Gerfen, 2015). The DLS receives inputs from sensorimotor cortex, while the DMS is innervated by associative regions of cortex.…”

Section: General Overviewmentioning

confidence: 99%

“…Are the cells in the striatum simply following cortical commands or does intrastriatal circuitry play a role in their activity? The topographical organization of the cortex is conveyed through its projections to the striatum and is proposed to persist through the basal ganglia in segregated information streams (Alexander et al, 1986; Dudman and Gerfen, 2015). Thus, cortical inputs could contribute to the creation of discrete functional units in part defined by their inputs.…”

Section: Spn Collateral Transmission Drives Lateral Inhibitionmentioning

confidence: 99%

Striatal Local Circuitry: A New Framework for Lateral Inhibition

Burke

Rotstein

Alvarez

2017

Neuron

212

209

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This Perspective will examine the organization of intrastriatal circuitry, review recent findings in this area, and discuss how the pattern of connectivity between striatal neurons might give rise to the behaviorally observed synergism between the direct/indirect pathway neurons. The emphasis of this Perspective is on the underappreciated role of lateral inhibition between striatal projection cells in controlling neuronal firing and shaping the output of this circuit. We review some classic studies in combination with more recent anatomical and functional findings to lay out a framework for an updated model of the local intra-striatal circuitry and its contribution to the formation of functional units of processing with the striatum and the integration and filtering of inputs to generate motor patterns and learned behaviors.

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The Basal Ganglia

Cited by 48 publications

References 268 publications

Behavioral evidence for feedback gain control by the inhibitory microcircuit of the substantia nigra

Behavioral evidence for feedback gain control by the inhibitory microcircuit of the substantia nigra

Loss of Dnmt3a dependent methylation in inhibitory neurons impairs neural function through a mechanism that impacts Rett syndrome

Striatal Local Circuitry: A New Framework for Lateral Inhibition

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