The Role of Integrin β3 in Nucleus Accumbens Function

Abstract

Stress disorders, depression, anxiety, and substance use disorder, are regulated by serotonin (5HT). The dorsal raphe nucleus (DRN), the major site for neuronal 5HT synthesis, sends projections to the nucleus accumbens (NAc). NAc glutamatergic synapse adaptations are consistent with changes in mood and reward, key components of stress disorders. A subpopulation of DRN projection neurons express the β3 subunit of the integrin αvβ3 receptor. The integrin αvβ3 receptor regulates extracellular 5HT concentration by modulation of 5HT transporters. Previous work has implicated this cell adhesion receptor in modulating stress, as mice lacking the β3 subunit have increased vulnerability to chronic stress. However, how NAc function is regulated by the DRN β3 subunit and contributes to maladaptive reward behaviors as seen in stress disorders is unknown.Because the β3 subunit of the integrin avβ3 receptor is only expressed in a subpopulation of 5HT neurons, this suggests that it confers a specific function to this neuronal population. Using a mouse line with selective deletion of the β3 subunit within 5HT neurons, we are able to characterize its role in 5HT synaptic transmission. Using acute brain slice whole‐cell patch‐clamp electrophysiology, we characterize how the β3 subunit of 5HT inputs contribute to glutamatergic NAc synaptic transmission. Our data suggests that selective deletion of the β3 subunit in 5HT neurons blunts excitatory synaptic strength in the NAc. This suggests that the β3 subunit in 5HT neurons modulates excitatory input to the NAc, which may relate to stress response.Support or Funding InformationNIH T32 5T32MH064913‐15This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.