Local D2- to D1-neuron transmodulation updates goal-directed learning in the striatum

Extinction learning allows animals to withhold voluntary actions that are no longer related to reward and so provides a major source of behavioral control. Although such learning is thought to depend on dopamine signals in the striatum, the way the circuits that mediate goal-directed control are reorganized during new learning remains unknown. Here, by mapping a dopamine-dependent transcriptional activation marker in large ensembles of spiny projection neurons (SPNs) expressing dopamine receptor type 1 (D1-SPNs) or 2 (D2-SPNs) in mice, we demonstrate an extensive and dynamic D2- to D1-SPN transmodulation across the striatum that is necessary for updating previous goal-directed learning. Our findings suggest that D2-SPNs suppress the influence of outdated D1-SPN plasticity within functionally relevant striatal territories to reshape volitional action.

Download Full-text

D1 and D2 systems converge in the striatum to update goal-directed learning

10.1101/780346 ◽

2019 ◽

Cited By ~ 1

Author(s):

Miriam Matamales ◽

Alice E. McGovern ◽

Jia Dai Mi ◽

Stuart B. Mazzone ◽

Bernard W. Balleine ◽

...

Keyword(s):

Transcriptional Activation ◽

Behavioral Control ◽

Dorsal Striatum ◽

Projection Neurons ◽

Extinction Learning ◽

Striatal Projection Neurons ◽

New Learning ◽

Large Ensembles ◽

Directed Learning

AbstractExtinction learning allows animals to withhold voluntary actions that are no longer related to reward and so provides a major source of behavioral control. Although such learning is thought to depend on dopamine signals in the striatum, the way the circuits mediating goal-directed control are reorganized during new learning remains unknown. Here, by mapping a dopamine-dependent transcriptional activation marker in large ensembles of striatal projection neurons (SPNs) expressing dopamine receptor type 1 (D1-SPNs) or 2 (D2-SPNs) in mice, we demonstrate an extensive and dynamic D2- to D1-SPN trans-modulation across the dorsal striatum that is necessary for updating previous goal-directed learning. Our findings suggest that D2-SPNs suppress the influence of outdated D1-SPN plasticity within functionally relevant striatal territories to reshape volitional action.

Download Full-text

Regulation des Angstverhaltens — zur Rolle neuronaler Netzwerke

BIOspektrum ◽

10.1007/s12268-019-0226-8 ◽

2019 ◽

Vol 25 (7) ◽

pp. 711-714

Author(s):

Nina Dedic ◽

Jan M. Deussing

Keyword(s):

Stress Response ◽

Ventral Tegmental Area ◽

Long Range ◽

Dopamine Release ◽

Receptor Type ◽

Projection Neurons ◽

Neuronal Circuit ◽

Brain Reward ◽

Crh Receptor Type 1

AbstractThe corticotropin-releasing hormone (CRH) system orchestrates the organism’s stress response including the regulation of adaptive be haviours. Here we describe a novel neuronal circuit, which acts anxiety suppressing and positively modulates dopamine release. This anxiolytic circuit comprises inhibitory CRH-expressing, long-range projection neurons within the extended amygdala. These neurons innervate the ventral tegmental area, a prominent brain reward center that expresses high levels of CRH receptor type 1.

Download Full-text

Constitutive activity of dopamine receptor type 1 (D1R) increases CaV2.2 currents in PFC neurons

The Journal of General Physiology ◽

10.1085/jgp.201912492 ◽

2020 ◽

Vol 152 (5) ◽

Author(s):

Clara Inés McCarthy ◽

Cambria Chou-Freed ◽

Silvia Susana Rodríguez ◽

Agustín Yaneff ◽

Carlos Davio ◽

...

Keyword(s):

Dopamine Receptor ◽

Pyramidal Neurons ◽

Critical Role ◽

Intraperitoneal Administration ◽

Brain Slices ◽

Physiological Role ◽

Receptor Type ◽

Constitutive Activity ◽

Medial Pfc

Alterations in dopamine receptor type 1 (D1R) density are associated with cognitive deficits of aging and schizophrenia. In the prefrontal cortex (PFC), D1R plays a critical role in the regulation of working memory, which is impaired in these cognitive deficit states, but the cellular events triggered by changes in D1R expression remain unknown. A previous report demonstrated that interaction between voltage-gated calcium channel type 2.2 (CaV2.2) and D1R stimulates CaV2.2 postsynaptic surface location in medial PFC pyramidal neurons. Here, we show that in addition to the occurrence of the physical receptor-channel interaction, constitutive D1R activity mediates up-regulation of functional CaV2.2 surface density. We performed patch-clamp experiments on transfected HEK293T cells and wild-type C57BL/6 mouse brain slices, as well as imaging experiments and cAMP measurements. We found that D1R coexpression led to ∼60% increase in CaV2.2 currents in HEK293T cells. This effect was occluded by preincubation with a D1/D5R inverse agonist, chlorpromazine, and by replacing D1R with a D1R mutant lacking constitutive activity. Moreover, D1R-induced increase in CaV2.2 currents required basally active Gs protein, as well as D1R-CaV2.2 interaction. In mice, intraperitoneal administration of chlorpromazine reduced native CaV currents’ sensitivity to ω-conotoxin-GVIA and their size by ∼49% in layer V/VI pyramidal neurons from medial PFC, indicating a selective effect on CaV2.2. Additionally, we found that reducing D1/D5R constitutive activity correlates with a decrease in the agonist-induced D1/D5R inhibitory effect on native CaV currents. Our results could be interpreted as a stimulatory effect of D1R constitutive activity on the number of CaV2.2 channels available for dopamine-mediated modulation. Our results contribute to the understanding of the physiological role of D1R constitutive activity and may explain the noncanonical postsynaptic distribution of functional CaV2.2 in PFC neurons.

Download Full-text