Optogenetic self-stimulation in the nucleus accumbens: D1 reward versus D2 ambivalence

Abstract

The nucleus accumbens (NAc) contains multiple subpopulations of medium spiny neurons (MSNs). One subpopulation expresses D1-type dopamine receptors, another expresses D2-type receptors, and a third expresses both. The relative roles in NAc of D1 neurons versus D2 neurons in appetitive motivation were assessed here. Specifically, we asked whether D1-Cre mice would instrumentally seek optogenetic self-stimulation specifically targeted at D1 MSNs in NAc, and similarly if D2-Cre mice would self-stimulate D2 neurons in NAc. Mice were implanted with Cre-targeted channelrhodopsin (ChR2) virus and optic fibers in NAc. Subsequently, mice could earn brief NAc laser illuminations by actively touching a metal spout in one task, or by going to a particular location in a separate task. Results indicated that D1 neuronal excitation in NAc supported intense self-stimulation in both tasks. D1-Cre mice earned hundreds to thousands of spout-touches per half-hour session, and also sought out locations that delivered NAc laser to excite D1 MSNs. By comparison, D2 ChR2 mice showed lower but still positive levels of self-stimulation in the spout-touch task, earning dozens to hundreds of NAc laser illuminations. However, in the location task, D2 mice failed to show positive self-stimulation. If anything, a few D2 individuals gradually avoided the laser location. Brain-wide measures indicated that D1 and D2 stimulations in NAc recruited heavily overlapping patterns of Fos activation in distant limbic structures. These results confirm that excitation of D1 MSNs in NAc supports strong incentive motivation to self-stimulate. They also suggest that excitation of D2 neurons in NAc supports self-stimulation under some conditions, but fails under others and possibly may even shift to negative avoidance.

Role of nucleus accumbens core but not shell in incubation of methamphetamine craving after voluntary abstinence

“…Furthermore, our data do not support the hypothesis that Drd1 and Drd2 MSNs act in opposing manner [73] but rather, suggests that a coincident and concerted MSNs activity is required for reward-related behaviors [74][75][76]. Indeed, regardless of the antagonist used in our experiments (SCH39166, Drd1selective; raclopride, Drd2-selective; flupenthixol, Drd1-Drd2-selective), we observed reliable reduction of incubation of methamphetamine craving.…”

Desire or Dread from Nucleus Accumbens Inhibitions: Reversed by Same-Site Optogenetic Excitations

“…We note that other studies have reported distant increases in Fos in VP, LH, and VTA to be induced by ChR2 stimulation of NAc MSN populations (Cole et al, 2018;Soares-Cunha et al, 2018).…”

“…Similarly, changes induced by DNQX microinjections were computed by comparison to a vehicle-microinjection baseline. For that, Fos was measured in equivalent sites in rats that received vehicle microinjections 90 min before perfusion (Castro and Berridge, 2017;Warlow et al, 2017;Cole et al, 2018).…”

The nucleus accumbens core is necessary to scale fear to degree of threat

“…The failure of NAcc inhibition to suppress nose poking may seem odd. Mice will readily perform actions that channelrhodopsin-excite NAcc D1 and D2 cell types (Cole et al, 2018), and rats will perform actions exciting glutamatergic inputs to the NAcc via channelrhodopsin (Stuber et al, 2011;Britt et al, 2012). However, these studies demonstrate that NAcc activity is sufficient, but not necessary, to support reward-seeking.…”