We aim to study a novel strategy to modulate and enhance cognitive flexibility through the selective activation of the postsynaptic 5-HT1AR in the PL. We will employ a multi-dimensional approach using state-of-art techniques in neuroscience. Using dual color fiber photometry, optogenetics, RNAscope, pharmacological approaches, and positron emission tomography (PET) imaging we will: (1) uncover the dynamics of neuronal activity changes in 5-HT1AR-expressing cells induced by PL 5-HT release during cognitive flexibility tasks; (2) determine the contribution of 5-HT1AR activation to the modulation of cognitive flexibility, and (3) assess 5-HT1AR activation as a neural correlate of cognitive (in)flexibility. We believe this research holds a greater and broader translational potential for upcoming therapeutic interventions to indirectly help to prevent suicidal behavior, aid in patient engagement in therapy, and directly tackle cognitive rigidity in individuals with neuropsychiatric disorders including depression, obsessive-compulsive disorder, and autism spectrum disorder.