Mixed representations of choice direction and outcome by GABA/glutamate cotransmitting neurons in the entopeduncular nucleus
The basal ganglia (BG) are an evolutionarily conserved and phylogenetically old set of sub-cortical nuclei that guide action selection, evaluation, and reinforcement. The entopeduncular nucleus (EP) is a major BG output nucleus that contains a population of GABA/glutamate cotransmitting neurons (EPS...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2025-01-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/100488 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832592126405246976 |
|---|---|
| author | Julianna Locantore Yijun Liu Jesse White Janet Berrios Wallace Celia Beron Emily Kraft Bernardo Sabatini Michael Wallace |
| author_facet | Julianna Locantore Yijun Liu Jesse White Janet Berrios Wallace Celia Beron Emily Kraft Bernardo Sabatini Michael Wallace |
| author_sort | Julianna Locantore |
| collection | DOAJ |
| description | The basal ganglia (BG) are an evolutionarily conserved and phylogenetically old set of sub-cortical nuclei that guide action selection, evaluation, and reinforcement. The entopeduncular nucleus (EP) is a major BG output nucleus that contains a population of GABA/glutamate cotransmitting neurons (EPSst+) that specifically target the lateral habenula (LHb) and whose function in behavior remains mysterious. Here, we use a probabilistic switching task that requires an animal to maintain flexible relationships between action selection and evaluation to examine when and how GABA/glutamate cotransmitting neurons contribute to behavior. We find that EPSst+ neurons are strongly engaged during this task and show bidirectional changes in activity during the choice and outcome periods of a trial. We then tested the effects of either permanently blocking cotransmission or modifying the GABA/glutamate ratio on behavior in well-trained animals. Neither manipulation produced detectable changes in behavior despite significant changes in synaptic transmission in the LHb, demonstrating that the outputs of these neurons are not required for ongoing action-outcome updating in a probabilistic switching task. |
| format | Article |
| id | doaj-art-1c2f8298cdf041898fdbf5add2c37293 |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-1c2f8298cdf041898fdbf5add2c372932025-01-21T13:13:01ZengeLife Sciences Publications LtdeLife2050-084X2025-01-011310.7554/eLife.100488Mixed representations of choice direction and outcome by GABA/glutamate cotransmitting neurons in the entopeduncular nucleusJulianna Locantore0Yijun Liu1https://orcid.org/0009-0000-5612-7666Jesse White2Janet Berrios Wallace3Celia Beron4https://orcid.org/0000-0003-4289-253XEmily Kraft5Bernardo Sabatini6https://orcid.org/0000-0003-0095-9177Michael Wallace7https://orcid.org/0000-0002-7270-8521Department of Anatomy and Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, United StatesDepartment of Anatomy and Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, United StatesDepartment of Anatomy and Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, United StatesHoward Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, United StatesHoward Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Anatomy and Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, United StatesHoward Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Anatomy and Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, United StatesThe basal ganglia (BG) are an evolutionarily conserved and phylogenetically old set of sub-cortical nuclei that guide action selection, evaluation, and reinforcement. The entopeduncular nucleus (EP) is a major BG output nucleus that contains a population of GABA/glutamate cotransmitting neurons (EPSst+) that specifically target the lateral habenula (LHb) and whose function in behavior remains mysterious. Here, we use a probabilistic switching task that requires an animal to maintain flexible relationships between action selection and evaluation to examine when and how GABA/glutamate cotransmitting neurons contribute to behavior. We find that EPSst+ neurons are strongly engaged during this task and show bidirectional changes in activity during the choice and outcome periods of a trial. We then tested the effects of either permanently blocking cotransmission or modifying the GABA/glutamate ratio on behavior in well-trained animals. Neither manipulation produced detectable changes in behavior despite significant changes in synaptic transmission in the LHb, demonstrating that the outputs of these neurons are not required for ongoing action-outcome updating in a probabilistic switching task.https://elifesciences.org/articles/100488basal gangliacotransmissiondecision making |
| spellingShingle | Julianna Locantore Yijun Liu Jesse White Janet Berrios Wallace Celia Beron Emily Kraft Bernardo Sabatini Michael Wallace Mixed representations of choice direction and outcome by GABA/glutamate cotransmitting neurons in the entopeduncular nucleus eLife basal ganglia cotransmission decision making |
| title | Mixed representations of choice direction and outcome by GABA/glutamate cotransmitting neurons in the entopeduncular nucleus |
| title_full | Mixed representations of choice direction and outcome by GABA/glutamate cotransmitting neurons in the entopeduncular nucleus |
| title_fullStr | Mixed representations of choice direction and outcome by GABA/glutamate cotransmitting neurons in the entopeduncular nucleus |
| title_full_unstemmed | Mixed representations of choice direction and outcome by GABA/glutamate cotransmitting neurons in the entopeduncular nucleus |
| title_short | Mixed representations of choice direction and outcome by GABA/glutamate cotransmitting neurons in the entopeduncular nucleus |
| title_sort | mixed representations of choice direction and outcome by gaba glutamate cotransmitting neurons in the entopeduncular nucleus |
| topic | basal ganglia cotransmission decision making |
| url | https://elifesciences.org/articles/100488 |
| work_keys_str_mv | AT juliannalocantore mixedrepresentationsofchoicedirectionandoutcomebygabaglutamatecotransmittingneuronsintheentopeduncularnucleus AT yijunliu mixedrepresentationsofchoicedirectionandoutcomebygabaglutamatecotransmittingneuronsintheentopeduncularnucleus AT jessewhite mixedrepresentationsofchoicedirectionandoutcomebygabaglutamatecotransmittingneuronsintheentopeduncularnucleus AT janetberrioswallace mixedrepresentationsofchoicedirectionandoutcomebygabaglutamatecotransmittingneuronsintheentopeduncularnucleus AT celiaberon mixedrepresentationsofchoicedirectionandoutcomebygabaglutamatecotransmittingneuronsintheentopeduncularnucleus AT emilykraft mixedrepresentationsofchoicedirectionandoutcomebygabaglutamatecotransmittingneuronsintheentopeduncularnucleus AT bernardosabatini mixedrepresentationsofchoicedirectionandoutcomebygabaglutamatecotransmittingneuronsintheentopeduncularnucleus AT michaelwallace mixedrepresentationsofchoicedirectionandoutcomebygabaglutamatecotransmittingneuronsintheentopeduncularnucleus |