{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Coimbra B"],"funding":["Fundação para a Ciência e a Tecnologia","Fundação Bial","“la Caixa” Foundation"],"pagination":["3084-3100"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9541203"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["99(11)"],"pubmed_abstract":["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."],"journal":["Journal of neuroscience research"],"pubmed_title":["Laterodorsal tegmentum-ventral tegmental area projections encode positive reinforcement signals."],"pmcid":["PMC9541203"],"funding_grant_id":["UIDP/50026/2020","UIDB/50026/2020","CEECIND/03887/2017","SFRH/BD/147066/2019","ID 100010434","PTDC/MED‐NEU/29071/2017","Bial 30/16","CEECIND/00922/2018","LCF/PR/HR20/52400020","NORTE‐01‐0145‐FEDER‐000013","NORTE‐01‐0145‐FEDER‐000023"],"pubmed_authors":["Sousa N","Soares-Cunha C","Coimbra B","Correia R","Domingues AV","Rodrigues AJ","Pinto L"],"additional_accession":[]},"is_claimable":false,"name":"Laterodorsal tegmentum-ventral tegmental area projections encode positive reinforcement signals.","description":"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.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Nov","modification":"2025-04-04T09:30:10.24Z","creation":"2025-04-04T09:30:10.24Z"},"accession":"S-EPMC9541203","cross_references":{"pubmed":["34374447"],"doi":["10.1002/jnr.24931"]}}