A Selective Role for Lmo4 in Cue-Reward Learning
The ability to use environmental cues to predict rewarding events is essential to survival. The basolateral amygdala (BLA) plays a central role in such forms of associative learning. Aberrant cue-reward learning is thought to underlie many psychopathologies, including addiction, so understanding the...
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| Veröffentlicht in: | The Journal of neuroscience 2015-07, Vol.35 (26), p.9638-9647 |
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| creator | Maiya, Rajani Mangieri, Regina A Morrisett, Richard A Heberlein, Ulrike Messing, Robert O |
| description | The ability to use environmental cues to predict rewarding events is essential to survival. The basolateral amygdala (BLA) plays a central role in such forms of associative learning. Aberrant cue-reward learning is thought to underlie many psychopathologies, including addiction, so understanding the underlying molecular mechanisms can inform strategies for intervention. The transcriptional regulator LIM-only 4 (LMO4) is highly expressed in pyramidal neurons of the BLA, where it plays an important role in fear learning. Because the BLA also contributes to cue-reward learning, we investigated the role of BLA LMO4 in this process using Lmo4-deficient mice and RNA interference. Lmo4-deficient mice showed a selective deficit in conditioned reinforcement. Knockdown of LMO4 in the BLA, but not in the nucleus accumbens, recapitulated this deficit in wild-type mice. Molecular and electrophysiological studies identified a deficit in dopamine D2 receptor signaling in the BLA of Lmo4-deficient mice. These results reveal a novel, LMO4-dependent transcriptional program within the BLA that is essential to cue-reward learning. |
| doi_str_mv | 10.1523/JNEUROSCI.1740-15.2015 |
| format | Article |
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The basolateral amygdala (BLA) plays a central role in such forms of associative learning. Aberrant cue-reward learning is thought to underlie many psychopathologies, including addiction, so understanding the underlying molecular mechanisms can inform strategies for intervention. The transcriptional regulator LIM-only 4 (LMO4) is highly expressed in pyramidal neurons of the BLA, where it plays an important role in fear learning. Because the BLA also contributes to cue-reward learning, we investigated the role of BLA LMO4 in this process using Lmo4-deficient mice and RNA interference. Lmo4-deficient mice showed a selective deficit in conditioned reinforcement. Knockdown of LMO4 in the BLA, but not in the nucleus accumbens, recapitulated this deficit in wild-type mice. Molecular and electrophysiological studies identified a deficit in dopamine D2 receptor signaling in the BLA of Lmo4-deficient mice. 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The basolateral amygdala (BLA) plays a central role in such forms of associative learning. Aberrant cue-reward learning is thought to underlie many psychopathologies, including addiction, so understanding the underlying molecular mechanisms can inform strategies for intervention. The transcriptional regulator LIM-only 4 (LMO4) is highly expressed in pyramidal neurons of the BLA, where it plays an important role in fear learning. Because the BLA also contributes to cue-reward learning, we investigated the role of BLA LMO4 in this process using Lmo4-deficient mice and RNA interference. Lmo4-deficient mice showed a selective deficit in conditioned reinforcement. Knockdown of LMO4 in the BLA, but not in the nucleus accumbens, recapitulated this deficit in wild-type mice. Molecular and electrophysiological studies identified a deficit in dopamine D2 receptor signaling in the BLA of Lmo4-deficient mice. These results reveal a novel, LMO4-dependent transcriptional program within the BLA that is essential to cue-reward learning.</description><subject>Adaptor Proteins, Signal Transducing - genetics</subject><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>Animals</subject><subject>Association Learning - physiology</subject><subject>Basolateral Nuclear Complex - cytology</subject><subject>Choice Behavior - physiology</subject><subject>Conditioning, Operant - physiology</subject><subject>Cues</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>Green Fluorescent Proteins - metabolism</subject><subject>In Vitro Techniques</subject><subject>LIM Domain Proteins - genetics</subject><subject>LIM Domain Proteins - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Neurons - physiology</subject><subject>Patch-Clamp Techniques</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Receptors, Dopamine D2 - genetics</subject><subject>Receptors, Dopamine D2 - metabolism</subject><subject>Reward</subject><subject>RNA, Small Interfering - genetics</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Sucrose - administration & dosage</subject><issn>0270-6474</issn><issn>1529-2401</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkN1LwzAUxYMobk7_hdFHXzqTNGnaF2EMPybFweaeQ5rczko_ZtJO_O_N2Bz6dOGec889_BAaEzwhnEZ3L68P6-ViNZtPiGA4JHxCMeFnaOjVNKQMk3M0xFTgMGaCDdCVcx8YY4GJuEQDGpOIeWGI8DRYQQW6K3cQLNsKgqK1QVa3LCibYNZDuIQvZU2QgbJN2Wyu0UWhKgc3xzlC68eHt9lzmC2e5rNpFmpGWBfqJDWcaoOViDEhBkAlyqSGAYMEM624AFPoAlTuK-U5FZopYXSheYxzxaMRuj_kbvu8BqOh6ayq5NaWtbLfslWl_K805bvctDvJeJLyOPUBt8cA23724DpZl05DVakG2t5J4j2Cck6Ft8YHq7atcxaK0xuC5R63POGWe9x-J_e4_eH4b8nT2S_f6Ac3kX01</recordid><startdate>20150701</startdate><enddate>20150701</enddate><creator>Maiya, Rajani</creator><creator>Mangieri, Regina A</creator><creator>Morrisett, Richard A</creator><creator>Heberlein, Ulrike</creator><creator>Messing, Robert O</creator><general>Society for Neuroscience</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5345-4431</orcidid><orcidid>https://orcid.org/0000-0003-1837-7175</orcidid></search><sort><creationdate>20150701</creationdate><title>A Selective Role for Lmo4 in Cue-Reward Learning</title><author>Maiya, Rajani ; 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The basolateral amygdala (BLA) plays a central role in such forms of associative learning. Aberrant cue-reward learning is thought to underlie many psychopathologies, including addiction, so understanding the underlying molecular mechanisms can inform strategies for intervention. The transcriptional regulator LIM-only 4 (LMO4) is highly expressed in pyramidal neurons of the BLA, where it plays an important role in fear learning. Because the BLA also contributes to cue-reward learning, we investigated the role of BLA LMO4 in this process using Lmo4-deficient mice and RNA interference. Lmo4-deficient mice showed a selective deficit in conditioned reinforcement. Knockdown of LMO4 in the BLA, but not in the nucleus accumbens, recapitulated this deficit in wild-type mice. Molecular and electrophysiological studies identified a deficit in dopamine D2 receptor signaling in the BLA of Lmo4-deficient mice. 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| subjects | Adaptor Proteins, Signal Transducing - genetics Adaptor Proteins, Signal Transducing - metabolism Animals Association Learning - physiology Basolateral Nuclear Complex - cytology Choice Behavior - physiology Conditioning, Operant - physiology Cues Green Fluorescent Proteins - genetics Green Fluorescent Proteins - metabolism In Vitro Techniques LIM Domain Proteins - genetics LIM Domain Proteins - metabolism Mice Mice, Inbred C57BL Mice, Transgenic Neurons - physiology Patch-Clamp Techniques Proto-Oncogene Proteins c-akt - metabolism Receptors, Dopamine D2 - genetics Receptors, Dopamine D2 - metabolism Reward RNA, Small Interfering - genetics RNA, Small Interfering - metabolism Sucrose - administration & dosage |
| title | A Selective Role for Lmo4 in Cue-Reward Learning |
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