Basal Ganglia Là Gì

Salk Institute for Biological Studies, United States; Okinawa Institute of Science and Technology, Japan; Erasmus Medical Center Rotterdam, Netherlands; Japan Society for the Promotion of Sciences, Japan; Centre National de la Recherbịt Scientifique (CNRS), Aix-Marseille Universibửa, France;
Cortico-basal ganglia-thalamocortical loops are largely conceived as parallel circuits that process limbic, associative, và sensorimotor information separately. Whether and how these functionally distinct loops interact remains unclear. Combining genetic & viral approaches, we systemically mapped the limbic và motor cortico-basal ganglia-thalamocortical loops in rodents. Despite largely closed loops within each functional domain name, we discovered a unidirectional influence of the limbic over the motor loop via ventral striatum-substantia nigra (SNr)-motor thalamus circuitry. Slice electrophysiology verifies that the projection from ventral striatum functionally inhibits nigro-thalamic SNr neurons. In vivo optogenetic stimulation of ventral or dorsolateral striatum khổng lồ SNr pathway modulates activity in medial prefrontal cortex (mPFC) and motor cortex (M1), respectively. However, whereas the dorsolateral striatum-SNr pathway exerts little impact on mPFC, activation of the ventral striatum-SNr pathway effectively alters M1 activity. These results demonstrate an open cortico-basal ganglia loop whereby limbic information could modulate motor output through ventral striatum control of M1.

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Cortico-basal ganglia circuits are crucial for emotional, cognitive, and sensorimotor functions in health and disease (Doya, 2000; Floresco, 2015; Gerdeman et al., 2003; Graybiel et al., 1994; Gunaydin và Kreitzer, 2016; Hikosaka et al., 2000; Jahanshahi et al., 2015; Jin & Costa, 2015; March&, 2010; Vaghi et al., 2017; Yin and Knowlton, 2006). Virtually all cortical regions project to the striatum, the main đầu vào nucleus of the basal ganglia, which plays an important role in guiding behavior (Hintiryan et al., 2016; Hooks et al., 2018; Voorn et al., 2004; Witten et al., 2010; Yin et al., 2009; Znamenskiy & Zador, 2013). For example, the ‘sensorimotor’ dorsolateral striatum (DLS), which receives inputs from motor cortex, plays a role in executing body toàn thân movements (Barbera et al., 2016; Rueda-Orozteo và Robbe, 2015; Yin, 2010). However, the ‘limbic’ ventral striatum (VS), which receives limbic but not motor cortical input, also alters behavioral output including locomotion activity, approach/avoidance behaviors, & recovery of skilled movement after spinal cord injury (Britt et al., 2012; Floresco, 2015; Saunders & Robinson, 2012; Sawada et al., 2015). These findings suggest that for a unified behavioral output, information across the different modalities must be integrated inkhổng lồ motor circuits lớn drive sầu action appropriately (Mogenson et al., 1980). Though some studies have implicated mechanisms for limbic-motor interactions in the dopaminergic system (Beier et al., 2015; Belin & Everitt, 2008; Haber et al., 2000; Lerner et al., 2015; Watabe-Uchida et al., 2012; Yang et al., 2018), how limbic information ultimately reaches motor circuitry remains largely unknown, as bởi vì the characteristics of its influence.

Cortico-basal ganglia-thalamocortical loops have been largely conceptualized as closed, functionally segregated loops, in which limbic, associative sầu, & sensorimotor information are processed in parallel (Alexander et al., 1986; Deniau et al., 1996; Haber, 2003; Klặng & Hikosaka, 2015; Montaron et al., 1996; Parent và Hazrati, 1995). Alternatively, older studies proposed a ‘funnel-like’ architecture for basal ganglia output, such that each loop provides some đầu vào lớn the motor circuit (Allen và Tsukahara, 1974; Kemp and Powell, 1971). A ‘partially-open’ loop architecture in the cortico-basal ganglia circuitry has been suggested from primate studies (Joel và Weiner, 1994; Kelly & Strichồng, 2004; Miyabỏ ra et al., 2006), but this previous evidence is incomplete và the precise anatomical basis underlying connections between functionally distinct loops has not been identified. This laông xã of clarity in the cortico-basal ganglia connections is due lớn technical limitations, which include the laông xã of sophisticated viral tools và the complicated geometry of basal ganglia nuclei. As a result, studies have largely focused on mapping monosynaptic inputs from cortex to lớn the striatum (Hintiryan et al., 2016; Hooks et al., 2018; Voorn et al., 2004), emphasizing the topographic organization at the level of cortico-striatal projections. To date, it is incompletely understood how these distinct ‘channels’ proceed through the rest of basal ganglia-thalamo-cortical circuitry và whether they interact at all.

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In the current study, we focused on limbic và motor cortico-basal ganglia loops that originate from the medial prefrontal cortex (mPFC) & primary motor cortex (M1). These limbic và motor loops provide a Model khổng lồ investigate how distinct cortico-basal ganglia loops are organized throughout basal ganglia output, which we mapped using multiple genetic và viral tracing tools. In addition to lớn the closed loop within each functional tên miền, we identified a novel one-way interaction across these cortico-basal ganglia loops, in which the limbic loop exerts a unidirectional influence over the motor loop that is mediated by ventral striatum-medial SNr-motor thalamus circuitry. Using slice physiology and optogenetics, we show that VS functionally inhibits medial SNr neurons that project khổng lồ motor thalamus. We then characterized the influence of limbic and motor striato-nigral outputs onto lớn downstream cortical targets by optogenetically activating striato-nigral terminals from VS or DLS and by recording neuronal activity in mPFC and M1. Consistent with our anatomical findings, the in vivo recording experiments showed, in addition to the within-loop activation in which VS activated mPFC và DLS activated M1, significant activation of M1 when VS terminals in the SNr were stimulated. Conversely, DLS output did not effectively modulate activity in mPFC. Together, these results demonstrate an open cortico-basal ganglia-thalamocortical loop through which VS can modulate M1 activity, providing new insights inlớn the limbic control over motor output in health và disease.

Trans-synaptic tracing using wild-type rabies virut reveals both closed and open cortico-basal ganglia-thalamocortical loops

To visualize the cortico-basal ganglia loops, we first mapped the input-output connections of the rodent striatum with the primary motor cortex (M1), secondary motor cortex (M2), và medial prefrontal cortex (mPFC) by injecting a mixture of cholera toxin b subunit (CTb, non-trans-synaptic, bi-directional tracer) & a retrogradely transported poly-synaptic, wild-type rabies virut (Wt-RABV) inkhổng lồ each cortical area in rats (see Materials and methods). This strategy allowed us khổng lồ compare the topography of the cortico-striatal input đầu vào with that of striatal output neurons that multi-synaptically connect to the same area of cortex via the canonical basal ganglia direct pathway (i.e. via striato-nigro-thalamo-cortical circuitry) (Figure 1A). Wt-RABV has been repeatedly validated as a means of trans-synaptically tracing circuits retrogradely, in a survival-time-dependent manner (Aoki et al., 2019; Kelly and Striông chồng, 2004; Suzuki et al., 2012; Ugolini, 2010). Prior studies have sầu established that 66–70 hr is adequate survival time for 3rd-order infection of Wt-RABV without 4th-order infection in rats (Aoki et al., 2019; Suzuki et al., 2012), so this procedure could determine tri-synaptic connections originating from striatum khổng lồ cortex via the direct pathway (Kelly và Striông xã, 2004; Miyachi et al., 2006).

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Trans-synaptic wild-type rabies tracing reveals both closed and open cortico-basal ganglia loops.
(A) The strategy khổng lồ label striatal neurons connecting to lớn the cerebral cortex by Wt-RABV trans-synaptic retrograde tracing, & CTb-based non-trans-synaptic anterograde tracing for mapping cortico-striatal terminals. (B) Example image of Wt-RABV/CTb injection inlớn M1 (left). After 66–70 hr of survival time, Wt-RABV was transfected up to lớn 3rd-order neurons, which were found in various striatal subregions (right). Scale bars, 1 milimet (left), 500 µm (right). (C) 3D-reconstruction of Wt-RABV+ striatal neurons from the M1 injection case shown in (B). The two different angles emphasize the presence of Wt-RABV+ neurons throughout all of the striatum (VS, DMS, DLS, và TS). (D) Schema of Wt-RABV/CTb injection in M1. (E) Anterogradely labeled CTb+ cortico-striatal terminals (green) & retrogradely labeled Wt-RABV+ striatal neurons (purple) from the M1 injection case shown in (B). (F) Density maps showing the distribution of Wt-RABV+ neurons throughout the striatum from M1 injection. Blaông chồng contours indicate approximate areas receiving cortico-striatal inputs from M1. Color maps indicate the intensity of Wt-RABV+ labeling. (G–I) The same analyses for Wt-RABV/CTb injection in M2. (J–L) The same analyses for Wt-RABV/CTb injection in mPFC. (M) Normalized distribution of Wt-RABV+ neurons across five sầu striatal regions (VMS, VLS, DMS, DLS, TS) showing differences depending on cortical injection sites (mPFC, n = 3; M2, n = 4; M1, n = 4). Data are expressed as mean ± SEM. Two-way ANOVA, Interaction (Injection site x Labeled striatal regions): F(8,40) = 8.208, p

Monosynaptic modified rabies tracing confirms the limbic-to-motor connectivity via the striato-nigro-thalamic pathway