Adolescent neurostimulation of dopamine circuit reverses genetic deficits in frontal cortex function

• DOI: 10.7554/elife.87414.3
• Publication Date: 2023-10-13T13:15:42Z
• Authors: Surjeet Mastwal; Xinjian Li; Rianne Stowell; Matthew Manion; Wenyu Zhang; Nam-Shik Kim; Ki-Jun Yoon; Hongjun Song; Guo-Li Ming; Kuan Hong Wang
• Keywords: Neurostimulation

Dopamine system dysfunction is implicated in adolescent-onset neuropsychiatric disorders. Although psychosis symptoms can be alleviated by antipsychotics, cognitive remain unresponsive and novel paradigms investigating the circuit substrates underlying deficits are critically needed. The frontal cortex its dopaminergic input from midbrain functions undergo maturational changes during adolescence. Here, we used mice carrying mutations Arc or Disc1 to model mesofrontal dopamine deficiencies test circuit-based neurostimulation strategies restore functions. We found that a memory-guided spatial navigation task, cortical neurons were activated coordinately at decision-making point wild-type but not -/- mice. Chemogenetic stimulation of optogenetic axons limited adolescent period consistently reversed genetic defects innervation, task-coordinated neuronal activity, adulthood. Furthermore, also same +/- Our findings reveal common alterations caused two different genes demonstrate feasibility reverse these behavioral deficits. These results may suggest developmental windows targets for treating neurodevelopmental