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. 2025 Oct 1;20(10):2913-2914.
doi: 10.4103/NRR.NRR-D-24-00759. Epub 2024 Sep 24.

Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

William J Flerlage  1 , Mark L Dell'Acqua  2 , Brian M Cox  1 , Fereshteh S Nugent  1
Affiliations

Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

William J Flerlage et al. Neural Regen Res. .
No abstract available

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Figures

Figure 1
Figure 1
Emerging roles of A-kinase anchoring protein 5 (AKAP5) signaling within reward circuits. Simplified schematic illustration demonstrating the key structures and their known interconnections within reward circuits where AKAP5 signaling may play an essential role in regulation of decision-making and goal-directed behaviors as well as in promotion of mood dysregulation and drug-related behaviors. The brain’s reward pathways comprise of a network of structures mediating reward, motivation, and reinforcement learning with the most important one, the mesocorticolimbic dopamine pathway, arising from the ventral tegmental area (VTA) dopamine neurons projecting to the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC). Other reward-related nuclei such as the lateral habenula (LHb), amygdala (AMG) and retrosplenial cortex (RSC) play an important role in encoding reward-related signals through their interconnectivity with the mesocorticolimbic dopamine pathway. In particular, LHb acts as an integrative hub relaying signals from forebrain limbic structures to brain monoaminergic systems including dopamine system. In this perspective review, we highlight a few but not all of the identified regulatory roles of AKAP5 and/or AKAP-anchored protein kinase A in synaptic function, neuronal excitability, reward-related behavior, depression and drug addiction. The figure was created based on a free saggital view of mouse brain (https://commons.wikimedia.org/wiki/File:Mouse_brain_sagittal.svg).
See this image and copyright information in PMC

References

    1. Bai X, Zhang K, Ou C, Mu Y, Chi D, Zhang J, Huang J, Li X, Zhang Y, Huang W, Ouyang H. AKAP150 from nucleus accumbens dopamine D1 and D2 receptor-expressing medium spiny neurons regulates morphine withdrawal. iScience. 2023;26:108227. - PMC - PubMed
    1. Bucko PJ, Scott JD. Drugs that regulate local cell signaling: AKAP targeting as a therapeutic option. Annu Rev Pharmacol Toxicol. 2021;61:361–379. - PubMed
    1. Chen M, Ma S, Liu H, Dong Y, Tang J, Ni Z, Tan Y, Duan C, Li H, Huang H, Li Y, Cao X, Lingle CJ, Yang Y, Hu H. Brain region–specific action of ketamine as a rapid antidepressant. Science. 2024;385:eado7010. - PMC - PubMed
    1. Corcoran KA, Leaderbrand K, Jovasevic V, Guedea AL, Kassam F, Radulovic J. Regulation of fear extinction versus other affective behaviors by discrete cortical scaffolding complexes associated with NR2B and PKA signaling. Transl Psychiatry. 2015;5:e657. - PMC - PubMed
    1. Flerlage WJ, Langlois LD, Rusnak M, Simmons SC, Gouty S, Armstrong RC, Cox BM, Symes AJ, Tsuda MC, Nugent FS. Involvement of lateral habenula dysfunction in repetitive mild traumatic brain injury-induced motivational deficits. J Neurotrauma. 2023;40:125–140. - PMC - PubMed

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