Dopamine D1 Receptor–Positive Neurons in the Lateral Nucleus of the Cerebellum Contribute to Cognitive Behavior

Locke, Timothy M.; Soden, Marta E.; Miller, Shannon M.; Hunker, Avery C.; Knakal, Cerise R; Licholai, Julia A.; Dhillon, Karn S.; Keene, C. Dirk; Zweifel, Larry S.; Carlson, Edward C.

doi:10.1016/j.biopsych.2018.01.019

Cited by 66 publications

(83 citation statements)

References 106 publications

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“…It is not only the higher cortical areas where DREADDs have been applied to study DA-regulated cognition. The importance of D 1 Rs located in the lateral nucleus of the cerebellum was demonstrated using hM4Di-mediated cerebellar stimulation in D 1 R-Cre mice to induce deficits on working memory and prepulse inhibition of the acoustic startle response (Locke et al, 2018).…”

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confidence: 99%

Modulating Dopamine Signaling and Behavior with Chemogenetics: Concepts, Progress, and Challenges

et al. 2019

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confidence: 99%

Modulating Dopamine Signaling and Behavior with Chemogenetics: Concepts, Progress, and Challenges

et al. 2019

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“…This neurotransmitter participates integrally in cellular signaling, which has a favorable effect on LTP in the hippocampus, striatum and amygdala (Baldwin, Sadeghian, & Kelley, ;). It has been described that dopamine promotes the processes of acquisition and storage of information during LTP, through the activation of D1 receptors (Granado et al, ; Lisman & Grace, ; Locke et al, ). Particularly, it has been demonstrated that gene inactivation of the D1 receptor (D1R –/–) in mice reduces the early (E–) and late (L–) phase of LTP in the CA1 region of the hippocampus, a critical brain region for the LTP.…”

Section: Discussionmentioning

confidence: 99%

The neuropeptide‐12 improves recognition memory and neuronal plasticity of the limbic system in old rats

Hernández-Hernández

Hernandez

Vázquez-Roque

et al. 2018

Synapse

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Aging is a stage of life where cognitive and motor functions are impaired. This is because oxidative and inflammatory processes exacerbate neurodegeneration, which affects dendritic morphology and neuronal communication of limbic regions with memory loss. Recently, the use of trophic substances has been proposed to prevent neuronal deterioration. The neuropeptide-12 (N-PEP-12) has been evaluated in elderly patients with dementia, showing improvements in cognitive tasks due to acts as a neurotrophic factor. In the present work, we evaluated the effect of N-PEP-12 on motor activity and recognition memory, as well as its effects on dendritic morphology and the immunoreactivity of GFAP, Synaptophysin (SYP), and BDNF in neurons of the prefrontal cortex (PFC), dorsal hippocampus (DH) and nucleus accumbens (NAcc) of aged rats. The results show that N-PEP-12 improved the recognition memory, but the motor activity was not modified compared to the control animals. N-PEP-12 increases the density of dendritic spines and the total dendritic length in neurons of the PFC (layers 3 and 5) and in DH (CA1 and CA3). Interestingly NAcc neurons showed a reduction in the number of dendritic spines. In the N-PEP-12 animals, when evaluating the immunoreactivity for SYP and BDNF, there was an increase in the three brain regions, while the mark for GFAP decreased significantly. Our results suggest that N-PEP-12 promotes neuronal plasticity in the limbic system of aged animals, which contributes to improving recognition memory. In this sense, N-PEP-12 can be considered as a pharmacological alternative to prevent or delay brain aging and control senile dementias.

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“…Moreover, PC-D2R-cKO mice had performance similar to control mice in accelerating rotarod, beam walking and coat-hanger tests, further indicating that motor routines and coordination were not altered in D2R-cKO ( Figures S8b-d). In addition to its role in movement control, the cerebellum also takes part in cognitive abilities, regulation of emotions and social interactions 5,6 . We therefore tested whether D2R deletion from PCs might alter social interactions using the 3-chamber test 44 .…”

Section: D2r Expressed In Purkinje Cells Regulate Preference For Socimentioning

confidence: 99%

“…The cerebellum is a brain area that has long been considered to be solely involved in coordination of voluntary movements including the control of posture, balance and gaze orientation 1,2 . However, increasing evidence indicates that the cerebellum also takes part in cognitive and emotional abilities as well as social interactions [3][4][5][6] . The control of these various components of motor, cognitive and affective behaviors is largely ascribed to its modular compartmentalization into functional independent units tightly modulated by monoaminergic inputs which signal arousal, salience and valence [7][8][9] .…”

Section: Introductionmentioning

confidence: 99%

Cerebellar dopamine D2 receptors regulate preference for social novelty

Cutando

Puighermanal

Castell

et al. 2019

Preprint

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The cerebellum, a primary center involved in the control of sensorimotor tasks, also contributes to higher cognitive functions including reward, emotion and social interaction. The regulation of these behaviors has been largely ascribed to the monoaminergic system in limbic regions.However, the contribution of cerebellar dopamine signaling in the modulation of these functions remains largely unknown due to the lack of precise characterization of cerebellar dopaminoceptive neurons. By combining cell type-specific transcriptomic and histological analyses, 3D imaging and electrophysiology we demonstrate that cerebellar dopamine D2 receptors (D2R) in mice are preferentially expressed in Purkinje cells (PCs). While activation of D2R regulate synaptic efficacy onto PCs, their deletion or overexpression in PCs bidirectionally controls preference for social novelty without affecting motor functions.Altogether, these findings demonstrate novel D2R's roles in PC function and causally link cerebellar D2R levels of expression to social behaviors.

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Dopamine D1 Receptor–Positive Neurons in the Lateral Nucleus of the Cerebellum Contribute to Cognitive Behavior

Abstract: Collectively, these data demonstrate a functional link between genetically distinct neurons in the LCN and cognitive behaviors.

Cited by 66 publications

References 106 publications

Modulating Dopamine Signaling and Behavior with Chemogenetics: Concepts, Progress, and Challenges

Modulating Dopamine Signaling and Behavior with Chemogenetics: Concepts, Progress, and Challenges

The neuropeptide‐12 improves recognition memory and neuronal plasticity of the limbic system in old rats

Cerebellar dopamine D2 receptors regulate preference for social novelty

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