Optogenetic excitation of LDTg axons in the VTA reinforces operant responding in rats

Abstract

The laterodorsal tegmental nucleus (LDTg) importantly contributes to regulating firing activity of midbrain dopamine neurons and forebrain dopamine levels. Whether excitation of LDTg afferents to the ventral tegmental area (VTA) can reinforce operant behavior in rats is not known. Rats received adeno-associated viral vectors encoding channelrhodopsin2 (ChR2) and EYFP or EYFP only into the LDTg and were implanted with bilateral optic probes aimed at the VTA. LDTg ChR2-infected rats, but not LDTg EYFP-infected rats acquired lever pressing to obtain photostimulation into the VTA. During reversal testing, where contingencies between response levers were reversed, LDTg ChR2-infected rats learned to press the alternate, now reinforced, lever within one session. Following pretreatment with the broad-spectrum dopamine receptor blocker flupenthixol LDTg ChR2-infected rats initiated lever-pressing with normal latencies and lever-pressed normally for the first ten minutes of the session. Lever-pressing rates were strongly reduced thereafter. These results provide further support for an important role of LDTg inputs to the VTA in appetitively motivated behaviors.

Keywords: Acetylcholine; Glutamate; Mesopontine; Pedunculopontine tegmental nucleus; Reward.