Dichotomous Regulation of Striatal Plasticity by Dynorphin
Autor: | Renzhi Yang, Rupa R. Lalchandani Tuan, Fuu-Jiun Hwang, Daniel W. Bloodgood, Dong Kong, Jun B. Ding |
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Jazyk: | angličtina |
Rok vydání: | 2022 |
Předmět: |
Long-Term Potentiation
Opioid Basic Behavioral and Social Science Medical and Health Sciences Dynorphins Article Basal Ganglia Cellular and Molecular Neuroscience Mice Dopamine D1 Receptors Behavioral and Social Science Animals kappa Molecular Biology Psychiatry Neuronal Plasticity Receptors Opioid kappa Receptors Dopamine D1 Psychology and Cognitive Sciences Neurosciences Biological Sciences Corpus Striatum Brain Disorders Psychiatry and Mental health Good Health and Well Being Neurological |
Zdroj: | Mol Psychiatry Molecular psychiatry, vol 28, iss 1 |
Popis: | Modulation of corticostriatal plasticity alters the information flow throughout basal ganglia circuits and represents a fundamental mechanism for motor learning, action selection, and reward. Synaptic plasticity in the striatal direct- and indirect-pathway spiny projection neurons (dSPNs and iSPNs) is regulated by two distinct networks of GPCR signaling cascades. While it is well-known that dopamine D2 and adenosine A2a receptors bi-directionally regulate iSPN plasticity, it remains unclear how D1 signaling modulation of synaptic plasticity is counteracted by dSPN-specific Gi signaling. Here, we show that striatal dynorphin selectively suppresses long-term potentiation (LTP) through Kappa Opioid Receptor (KOR) signaling in dSPNs. Both KOR antagonism and conditional deletion of dynorphin in dSPNs enhance LTP counterbalancing with different levels of D1 receptor activation. Behaviorally, mice lacking dynorphin in D1 neurons show comparable motor behavior and reward-based learning, but enhanced flexibility during reversal learning. These findings support a model in which D1R and KOR signaling bi-directionally modulate synaptic plasticity and behavior in the direct pathway. |
Databáze: | OpenAIRE |
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