VTA and NAcc neurons inhibition during reversal learning: A pharmacological and an optogenetic approach

Abstract

Purpose: The aim of this study was to understand the contribution of VTA and Nacc cells in reversal learning performance by using two approaches. First, inhibition of VTA and Nacc cells using a Gaba-a agonist (Muscimol). Second, inhibition of VTA and Nacc cells using light-sensitive opsins (halorhodopsin). The prediction from this investigation was that neuronal suppression of Nacc neurons would have a greater impact on reversal learning performance than suppression of VTA cells, as task complexity increased. Methods: Rats (Muscimol group) (n = 15) were implanted with bilateral guide cannulae above the VTA and Nacc. Another group of rats (n = 15) received injections of lentivirus (halorhodopsin) in the VTA and Nacc, and were implanted with a fiber guide system that would deliver a yellow light to target neurons via an optical fiber. After surgery, rats were trained to complete an FR1 discrimination, and then tested in a between reversal and a within session reversal task. Results: VTA (n = 5) and Nacc (n = 5) implanted rats that received muscimol injections made significantly fewer errors during the between reversal session than the control group (saline, n = 5): F(1,14) = 42.885, p < 0.001. VTA rats also took significantly longer than the control group to reach criterion: F(1,14) = 4.933, p < 0.05. However, Nacc rats made significantly more errors than the control group during the more complex within session reversal F(1,14) = 7.031, p < 0.05. Conclusion: Our preliminary results suggest that NAcc neurons play an instrumental role in reversal learning performance, especially when task complexity increases. The high temporal resolution provided by the optical inhibition of NAcc and VTA neurons (via halorhodopsin) will provide us with answers about the importance of feedback information when an error is made.