Lesions of the Patch Compartment of Dorsolateral Striatum Disrupt Stimulus–Response Learning

Jenrette, Terrell; Logue, Jordan; Horner, Kristen A.

doi:10.1016/j.neuroscience.2019.07.033

Cited by 20 publications

(26 citation statements)

References 60 publications

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“…Interestingly, behavioral experiments show that electrical stimulation of striosomes reinforces actions (White and Hiroi, 1998) and striosomal ablation impairs habit learning (Jenrette et al, 2019). Because dopamine is required for learning, these findings may seem counter-intuitive as we have shown that the striosomes strongly inhibit dopamine neurons.…”

Section: What Is the Significance Of Striosomal Inhibition And Dopamimentioning

confidence: 85%

“…Because SNc dopamine neurons form a reciprocal loop with the dorsal striatum, dopamine rebound may represent a mechanism by which striosomes can control the timing of phasic dopamine signals in the striatum and therefore control the plasticity of their own synapses. Future work is needed to test whether self-contained dopamine rebound activity is related to the role striosomes play in repetitive behaviors (Bouchekioua et al, 2018;Canales and Graybiel, 2000) and persistent (devaluation-resistant) stimulus-response learning (Jenrette et al, 2019).…”

Section: What Is the Significance Of Striosomal Inhibition And Dopamimentioning

confidence: 99%

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Functional dissection of basal ganglia inhibitory input onto SNc dopaminergic neurons

Evans

Twedell

Zhu

et al. 2019

Preprint

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Substania nigra (SNc) dopaminergic neurons show a pause-rebound firing pattern in response to aversive events. Because these neurons integrate information from predominately inhibitory brain areas, it is important to determine which inputs functionally inhibit the dopamine neurons and whether this pause-rebound firing pattern can be produced by a solely inhibitory input. Here, we functionally map geneticallydefined inhibitory projections from the dorsal striatum (striosome and matrix) and globus pallidus (GPe; parvalbumin and Lhx6) onto SNc neurons. We find that GPe and striosomal inputs both pause firing in SNc neurons, but rebound firing only occurs after inhibition from striosomes. Indeed, we find that striosomes are synaptically optimized to produce rebound and preferentially inhibit a subpopulation of ventral, intrinsically rebound-ready SNc dopaminergic neurons on their reticulata dendrites. Therefore, we describe a self-contained dendrite-specific striatonigral circuit that can produce pauserebound firing in the absence of excitatory input.

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Section: What Is the Significance Of Striosomal Inhibition And Dopamimentioning

confidence: 85%

Section: What Is the Significance Of Striosomal Inhibition And Dopamimentioning

confidence: 99%

Functional dissection of basal ganglia inhibitory input onto SNc dopaminergic neurons

Evans

Twedell

Zhu

et al. 2019

Preprint

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“…The striatum is a key locus in the transition from flexible to habitual strategies, but less is known about how particular striatal subcircuits contribute to this phenomenon. Previous studies have implicated striatal patches, or striosomes, in this process (Canales and Graybiel, 2000; Murray et al, 2015, 2014), and more recent work has demonstrated that intact patches are necessary for normal habit formation (Jenrette et al, 2019; Nadel et al, 2020). The current work further addresses the role of patches in habit through use of optogenetics to modulate patch neuron activity in a temporally-precise manner during habit formation.…”

Section: Discussionmentioning

confidence: 99%

“…Early studies suggested that psychostimulant-induced stereotypy is linked to activity in patches (Canales and Graybiel, 2000; Murray et al, 2015, 2014) and that lesions of patches disrupt this stereotypy (Murray et al, 2015, 2014). More recently, striatal patches have been shown to be necessary for normal habit formation: specific lesions of patch neurons diminish habitual responding following reward devaluation (Jenrette et al, 2019) or changes in action-outcome contingencies (Nadel et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Optogenetic interrogation of the role of striatal patches in habit formation and inhibition of striatal dopamine

Nadel

Pawelko²,

Scott³

et al. 2020

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Habits are inflexible behaviors that can be maladaptive in diseases including drug addiction. The striatum is integral to habit formation, and interspersed throughout the striatum are patches, or striosomes, which are characterized by unique gene expression relative to the surrounding matrix. Recent work has indicated that patches are necessary for habit formation, but how patches contribute to habits remains partially understood. Here, using optogenetics, we modulated striatal patches in Sepw1-NP67 mice during habit formation. We find that patch activation during operant training impairs habit formation, and conversely, that acute patch stimulation after reward devaluation can drive habitual reward seeking. Patch stimulation invigorates general locomotion but is not inherently rewarding. Finally, we use fast-scan cyclic voltammetry to demonstrate that patch stimulation suppresses dopamine release in dorsal striatum in vivo. Overall, this work provides novel insight into the role of the patch compartment in habit formation, and potential interactions with dopamine signaling.

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“…Striosome and matrix neurons also differ in their electrophysiologic properties 26 and further mediate functions based on their connectivity 27 . The striosome compartment has been specifically associated with stimulus-response learning 28 and perhaps stereotypy 29,30 . Most recently, striosome neurons were identified as the major contributors to the nigrostriatal tract arising from dMSNs 27 .…”

Section: Introductionmentioning

confidence: 99%

Transcriptional and epigenetic characterization of early striosomes identifies Foxf2 and Olig2 as factors required for development of striatal compartmentation and neuronal phenotypic differentiation

Cirnaru

Song

Tshilenge

et al. 2020

Preprint

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The basal ganglia, best known for processing information required for multiple aspects of movement, is also part of a network which regulates reward and cognition. The major output nucleus of the basal ganglia is the striatum, and its functions are dependent on neuronal compartmentation, including striosomes and matrix, which are selectively affected in disease.Striatal projection neurons are GABAergic medium spiny neurons (MSNs), all of which share basic molecular signatures but are subtyped by selective expression of receptors, neuropeptides, and other gene families. Neurogenesis of the striosome and matrix occurs in separate waves, but the factors regulating terminal neuronal differentiation following migration are largely unidentified.We performed RNA--and ATAC--seq on sorted murine striosome and matrix cells at postnatal day 3. Focusing on the striosomal compartment, we validated the localization and role of transcription factors and their regulator(s), previously not known to be associated with striatal development, including Irx1, Foxf2, Olig2 and Stat1/2. In addition, we validated the enhancer function of a striosome--specific open chromatin region located 15Kb downstream of the Olig2 gene. These data and data bases provide novel tools to dissect and manipulate the networks regulating MSN compartmentation and differentiation and thus provide new approaches to establishing MSN subtypes from human iPSCs for disease modeling and drug discovery.

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Lesions of the Patch Compartment of Dorsolateral Striatum Disrupt Stimulus–Response Learning

Cited by 20 publications

References 60 publications

Functional dissection of basal ganglia inhibitory input onto SNc dopaminergic neurons

Functional dissection of basal ganglia inhibitory input onto SNc dopaminergic neurons

Optogenetic interrogation of the role of striatal patches in habit formation and inhibition of striatal dopamine

Transcriptional and epigenetic characterization of early striosomes identifies Foxf2 and Olig2 as factors required for development of striatal compartmentation and neuronal phenotypic differentiation

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