Adolescent alcohol exposure promotes mechanical allodynia and alters synaptic function at inputs from the basolateral amygdala to the prelimbic cortex
Binge drinking is common among adolescents despite mounting evidence linking it to various adverse health outcomes that include heightened pain perception. The prelimbic (PrL) cortex is vulnerable to insult from adolescent alcohol exposure and receives input from the basolateral amygdala (BLA) while...
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eLife Sciences Publications Ltd
2025-05-01
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| Online Access: | https://elifesciences.org/articles/101667 |
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| author | J Daniel Obray Erik T Wilkes Mike Scofield L Judson Chandler |
| author_facet | J Daniel Obray Erik T Wilkes Mike Scofield L Judson Chandler |
| author_sort | J Daniel Obray |
| collection | DOAJ |
| description | Binge drinking is common among adolescents despite mounting evidence linking it to various adverse health outcomes that include heightened pain perception. The prelimbic (PrL) cortex is vulnerable to insult from adolescent alcohol exposure and receives input from the basolateral amygdala (BLA) while sending projections to the ventrolateral periaqueductal gray (vlPAG) – two brain regions implicated in nociception. In this study, adolescent intermittent ethanol (AIE) exposure was carried out in male and female rats using a vapor inhalation procedure. Assessments of mechanical and thermal sensitivity revealed that AIE exposure-induced protracted mechanical allodynia. To investigate synaptic function at BLA inputs onto defined populations of PrL neurons, retrobeads and viral labeling were combined with optogenetics and slice electrophysiology. Recordings from retrobead labeled cells in the PrL revealed AIE reduced BLA-driven feedforward inhibition of neurons projecting from the PrL to the vlPAG, resulting in augmented excitation/inhibition (E/I) balance and increased intrinsic excitability. Consistent with this finding, recordings from virally tagged PrL parvalbumin interneurons (PVINs) demonstrated that AIE exposure reduced both E/I balance at BLA inputs onto PVINs and PVIN intrinsic excitability. These findings provide compelling evidence that AIE alters synaptic function and intrinsic excitability within a prefrontal nociceptive circuit. |
| format | Article |
| id | doaj-art-4edc7cc41aa44755b95fdc99a6ac3176 |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj-art-4edc7cc41aa44755b95fdc99a6ac31762025-08-20T03:48:51ZengeLife Sciences Publications LtdeLife2050-084X2025-05-011310.7554/eLife.101667Adolescent alcohol exposure promotes mechanical allodynia and alters synaptic function at inputs from the basolateral amygdala to the prelimbic cortexJ Daniel Obray0https://orcid.org/0000-0001-7526-4869Erik T Wilkes1Mike Scofield2https://orcid.org/0000-0002-2330-6999L Judson Chandler3https://orcid.org/0000-0002-1468-7320Department of Neuroscience, Medical University of South Carolina, Charleston, United StatesDepartment of Neuroscience, Medical University of South Carolina, Charleston, United StatesDepartment of Neuroscience, Medical University of South Carolina, Charleston, United States; Department of Anesthesia and Perioperative Medicine, Medical University of South Carolina, Charleston, United StatesDepartment of Neuroscience, Medical University of South Carolina, Charleston, United StatesBinge drinking is common among adolescents despite mounting evidence linking it to various adverse health outcomes that include heightened pain perception. The prelimbic (PrL) cortex is vulnerable to insult from adolescent alcohol exposure and receives input from the basolateral amygdala (BLA) while sending projections to the ventrolateral periaqueductal gray (vlPAG) – two brain regions implicated in nociception. In this study, adolescent intermittent ethanol (AIE) exposure was carried out in male and female rats using a vapor inhalation procedure. Assessments of mechanical and thermal sensitivity revealed that AIE exposure-induced protracted mechanical allodynia. To investigate synaptic function at BLA inputs onto defined populations of PrL neurons, retrobeads and viral labeling were combined with optogenetics and slice electrophysiology. Recordings from retrobead labeled cells in the PrL revealed AIE reduced BLA-driven feedforward inhibition of neurons projecting from the PrL to the vlPAG, resulting in augmented excitation/inhibition (E/I) balance and increased intrinsic excitability. Consistent with this finding, recordings from virally tagged PrL parvalbumin interneurons (PVINs) demonstrated that AIE exposure reduced both E/I balance at BLA inputs onto PVINs and PVIN intrinsic excitability. These findings provide compelling evidence that AIE alters synaptic function and intrinsic excitability within a prefrontal nociceptive circuit.https://elifesciences.org/articles/101667adolescent alcoholAIEpainallodyniaprefrontal cortexperiaqueductal gray |
| spellingShingle | J Daniel Obray Erik T Wilkes Mike Scofield L Judson Chandler Adolescent alcohol exposure promotes mechanical allodynia and alters synaptic function at inputs from the basolateral amygdala to the prelimbic cortex eLife adolescent alcohol AIE pain allodynia prefrontal cortex periaqueductal gray |
| title | Adolescent alcohol exposure promotes mechanical allodynia and alters synaptic function at inputs from the basolateral amygdala to the prelimbic cortex |
| title_full | Adolescent alcohol exposure promotes mechanical allodynia and alters synaptic function at inputs from the basolateral amygdala to the prelimbic cortex |
| title_fullStr | Adolescent alcohol exposure promotes mechanical allodynia and alters synaptic function at inputs from the basolateral amygdala to the prelimbic cortex |
| title_full_unstemmed | Adolescent alcohol exposure promotes mechanical allodynia and alters synaptic function at inputs from the basolateral amygdala to the prelimbic cortex |
| title_short | Adolescent alcohol exposure promotes mechanical allodynia and alters synaptic function at inputs from the basolateral amygdala to the prelimbic cortex |
| title_sort | adolescent alcohol exposure promotes mechanical allodynia and alters synaptic function at inputs from the basolateral amygdala to the prelimbic cortex |
| topic | adolescent alcohol AIE pain allodynia prefrontal cortex periaqueductal gray |
| url | https://elifesciences.org/articles/101667 |
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