Journal
JOURNAL OF NEUROSCIENCE RESEARCH
Volume 99, Issue 11, Pages 3084-3100Publisher
WILEY
DOI: 10.1002/jnr.24931
Keywords
LDT; motivation; neuronal circuits; optogenetics; reward
Categories
Funding
- Foundation for Science and Technology (FCT) [CEECIND/03887/2017, CEECIND/00922/2018]
- BIAL Foundation Grant [Bial 30/16]
- la Caixa Foundation [100010434, LCF/PR/HR20/52400020]
- FCT [SFRH/BD/147066/2019, PTDC/MED-NEU/29071/2017, UIDB/50026/2020, UIDP/50026/2020]
- [NORTE-01-0145-FEDER-000013]
- [NORTE-01-0145-FEDER-000023]
- Fundação para a Ciência e a Tecnologia [PTDC/MED-NEU/29071/2017, SFRH/BD/147066/2019] Funding Source: FCT
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Through experiments, it was found that activating LDT-VTA projections can amplify preference for the reward paired with laser stimulation, while LDT-VTA activation increases motivation and willingness to work for rewards associated with stimulation, indicating that LDT-VTA inputs encode positive reinforcement signals and play a crucial role in reward-related behaviors.
The laterodorsal tegmentum (LDT) is a brainstem nucleus classically involved in REM sleep and attention, and that has recently been associated with reward-related behaviors, as it controls the activity of ventral tegmental area (VTA) dopaminergic neurons, modulating dopamine release in the nucleus accumbens. To further understand the role of LDT-VTA inputs in reinforcement, we optogenetically manipulated these inputs during different behavioral paradigms in male rats. We found that in a two-choice instrumental task, optical activation of LDT-VTA projections shifts and amplifies preference to the laser-paired reward in comparison to an otherwise equal reward; the opposite was observed with inhibition experiments. In a progressive ratio task, LDT-VTA activation boosts motivation, that is, enhances the willingness to work to get the reward associated with LDT-VTA stimulation; and the reverse occurs when inhibiting these inputs. Animals abolished preference if the reward was omitted, suggesting that LDT-VTA stimulation adds/decreases value to the stimulation-paired reward. In addition, we show that LDT-VTA optical activation induces robust preference in the conditioned and real-time place preference tests, while optical inhibition induces aversion. The behavioral findings are supported by electrophysiological recordings and c-fos immunofluorescence correlates in downstream target regions. In LDT-VTA ChR2 animals, we observed an increase in the recruitment of lateral VTA dopamine neurons and D1 neurons from nucleus accumbens core and shell; whereas in LDT-VTA NpHR animals, D2 neurons appear to be preferentially recruited. Collectively, these data show that the LDT-VTA inputs encode positive reinforcement signals and are important for different dimensions of reward-related behaviors.
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