Cognitive effects of thalamostriatal degeneration are ameliorated by normalizing striatal cholinergic activity

Becchi, Serena; Chieng, Billy; Bradfield, Laura A.; Capellán, Roberto; Leung, Beatrice K.; Balleine, Bernard W.

doi:10.1101/2022.08.25.505358

Cited by 3 publications

(2 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5E-G). This is consistent with a recent study that showed that reversal learning increased the burst firing of DMS CINs [40].…”

Section: Resultssupporting

confidence: 93%

Dynamic Responses of Striatal Cholinergic Interneurons Control the Extinction and Updating of Goal-Directed Learning

Huang,

Chen,

et al. 2023

Preprint

View full text Add to dashboard Cite

Striatal cholinergic interneurons (CINs) regulate behavioral flexibility, but their exact contribution to this process remains elusive. In this study, we report that extinction learning enhances acetylcholine (ACh) release. Mimicking this enhancement by optogenetically inducing CIN burst firing promotes extinction learning. CINs receive excitatory thalamic inputs, and we observed that extinction training augmented thalamic activity. Optogenetically stimulating these thalamic inputs caused CIN burst firing and enhanced ACh release, strengthening extinction learning. Notably, CIN burst firing is usually followed by a pause in firing. We found that disrupting this pause through continuous optogenetic stimulation reversibly impaired the updating of goal-directed behaviors. Furthermore, excessive alcohol consumption reduced thalamus-induced burst-pause firing in CINs and impaired the reversal of goal-directed learning. In summary, thalamic-driven CIN burst firing promotes extinction learning, while the pause is pivotal for reversing goal-directed behavior, a process impacted by excessive alcohol. These findings shed light on how CIN’s dynamic responses affect behavioral flexibility.HighlightsH1.Burstfiring of CINs promotes extinction learningH2. Thalamic-CINexcitationenhances extinction learningH3.Pauseof CIN is critical for the reversal of goal-directed learningH4. Chronic alcohol consumption reduces theburst-pauseofCINsand impairs the reversal of goal-directed learning.

show abstract

“…5E-G). This is consistent with a recent study that showed that reversal learning increased the burst firing of DMS CINs [40].…”

Section: Resultssupporting

confidence: 93%

Dynamic Responses of Striatal Cholinergic Interneurons Control the Extinction and Updating of Goal-Directed Learning

Huang,

Chen,

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Activation of thalamostriatal system has been shown to alleviate deficits in motor functions in PD model mice through striatal cholinergic interneurons 64,65 . In addition, blocking neuroinflammation in the Pf rescues cognitive impairment in PD model rats 66 . Thus, the CM/Pf complex may be a potential, effective target for therapeutic strategies for the symptoms of PD.…”

Section: Discussionmentioning

confidence: 99%

Distinct roles of two thalamostriatal systems in learning processes of visual discrimination in common marmosets

Kato,

Sugawara,

Yamasaki

et al. 2024

Preprint

View full text Add to dashboard Cite

The thalamostriatal projections arising from the intralaminar thalamic nuclei (ILN) constitute the principal source of input information to specified subregions of the striatum, a key structure of the cortico-basal ganglia circuitry. However, the roles of primate ILN in cortico-basal ganglia circuit functions remain unclear. Here, we performed immunotoxin-induced selective targeting of two representative structures of the ILN, the parafascicular nucleus (Pf) and centre médian nucleus (CM) projecting to the caudate nucleus (Cd) and putamen (Pu), respectively, in common marmosets. Elimination of Pf-Cd neurons resulted in impaired reversal learning of a two-choice visual discrimination task, whereas removal of CM-Pu neurons disturbed the task acquisition. No marked impact of such manipulations was observed on either motor skill learning or spontaneous locomotor activity. Our findings reveal that the two thalamostriatal systems play distinct roles in the learning processes of external cue-dependent decision-making in nonhuman primates.

show abstract

Striatal Acetylcholine and Dopamine Interactions Produce Situationappropriate Action Selection

Bradfield,

Becchi,

Kendig

2024

View full text Add to dashboard Cite

Individuals often learn how to perform new actions for particular outcomes against a complex background of existing action-outcome associations. As such, this new knowledge can interfere or even compete with existing knowledge, such that individuals must use internal and external cues to determine which action is appropriate to the current situation. The question thus remains as to how this problem is solved at a neural level. Research over the last decade or so has begun to determine how the brain achieves situation-appropriate action selection. Several converging lines of evidence suggest that it is achieved through the complex interactions of acetylcholine and dopamine within the striatum in a manner that relies on glutamatergic inputs from the cortex and thalamus. Here we briefly review this evidence, then relate it to several very recent findings to provide new, speculative insights regarding the precise nature of striatal acetylcholine/dopamine interaction dynamics and their relation to situation-appropriate action selection.

show abstract

Cognitive effects of thalamostriatal degeneration are ameliorated by normalizing striatal cholinergic activity

Cited by 3 publications

References 62 publications

Dynamic Responses of Striatal Cholinergic Interneurons Control the Extinction and Updating of Goal-Directed Learning

Dynamic Responses of Striatal Cholinergic Interneurons Control the Extinction and Updating of Goal-Directed Learning

Distinct roles of two thalamostriatal systems in learning processes of visual discrimination in common marmosets

Striatal Acetylcholine and Dopamine Interactions Produce Situationappropriate Action Selection

Contact Info

Product

Resources

About