Michaela E. Price, Hailey X. Egido-Betancourt, Sarah E. Sizer, Brian P. Parrish, Nancy J. Alexander, Kimberly F. Raab-Graham, Brian A. McCool
{"title":"慢性间歇乙醇和戒断抑制诱发和自发GABA释放到基底外侧杏仁核主要神经元的不同种群","authors":"Michaela E. Price, Hailey X. Egido-Betancourt, Sarah E. Sizer, Brian P. Parrish, Nancy J. Alexander, Kimberly F. Raab-Graham, Brian A. McCool","doi":"10.1111/adb.70080","DOIUrl":null,"url":null,"abstract":"<p>Unique populations of basolateral amygdala (BLA) neurons regulate anxiety and reward through projections targeting downstream regions like the bed nucleus of the stria terminalis (BNST) and nucleus accumbens (NAC). We showed previously that withdrawal from chronic ethanol exposure (CIE/WD) produced population- and sex-specific alterations to distinct glutamatergic inputs. The current study examined GABAergic function in these distinct populations (BLA<sup>NAC</sup> and BLA<sup>BNST</sup> neurons). We found that CIE/WD diminished feed-forward GABA release from lateral paracapsular cells (LPCs) specifically onto male BLA<sup>NAC</sup> neurons. Pharmacological manipulations showed this dysregulation was caused by the enhanced activity of μ-opioid receptors. CIE/WD did not alter evoked GABA release from local interneurons onto either population. However, females expressed greater GABA release from these local interneurons compared to males. Immunostaining and confocal microscopy revealed lower colocalization between the GABA vesicular transporter, vGAT and parvalbumin in females, indicating that greater GABA releases from local interneurons in this sex may be a compensatory response to lower levels of perisomatic innervation by PV<sup>+</sup> interneurons. Consistent with this, there were no sex differences related to spontaneous GABAergic synaptic events although CIE/WD decreased their frequency specifically in BLA<sup>BNST</sup> neurons from both sexes. Altogether, these findings demonstrate that CIE/WD dynamically alters GABAergic function in an input-, sex- and population-specific fashion. Moreover, there are basal sex differences in both the anatomy of BLA GABAergic synapses and their function.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 9","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70080","citationCount":"0","resultStr":"{\"title\":\"Chronic Intermittent Ethanol and Withdrawal Suppress Evoked and Spontaneous GABA Release Onto Distinct Populations of Basolateral Amygdala Principal Neurons\",\"authors\":\"Michaela E. Price, Hailey X. Egido-Betancourt, Sarah E. Sizer, Brian P. Parrish, Nancy J. Alexander, Kimberly F. Raab-Graham, Brian A. 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However, females expressed greater GABA release from these local interneurons compared to males. Immunostaining and confocal microscopy revealed lower colocalization between the GABA vesicular transporter, vGAT and parvalbumin in females, indicating that greater GABA releases from local interneurons in this sex may be a compensatory response to lower levels of perisomatic innervation by PV<sup>+</sup> interneurons. Consistent with this, there were no sex differences related to spontaneous GABAergic synaptic events although CIE/WD decreased their frequency specifically in BLA<sup>BNST</sup> neurons from both sexes. Altogether, these findings demonstrate that CIE/WD dynamically alters GABAergic function in an input-, sex- and population-specific fashion. 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Chronic Intermittent Ethanol and Withdrawal Suppress Evoked and Spontaneous GABA Release Onto Distinct Populations of Basolateral Amygdala Principal Neurons
Unique populations of basolateral amygdala (BLA) neurons regulate anxiety and reward through projections targeting downstream regions like the bed nucleus of the stria terminalis (BNST) and nucleus accumbens (NAC). We showed previously that withdrawal from chronic ethanol exposure (CIE/WD) produced population- and sex-specific alterations to distinct glutamatergic inputs. The current study examined GABAergic function in these distinct populations (BLANAC and BLABNST neurons). We found that CIE/WD diminished feed-forward GABA release from lateral paracapsular cells (LPCs) specifically onto male BLANAC neurons. Pharmacological manipulations showed this dysregulation was caused by the enhanced activity of μ-opioid receptors. CIE/WD did not alter evoked GABA release from local interneurons onto either population. However, females expressed greater GABA release from these local interneurons compared to males. Immunostaining and confocal microscopy revealed lower colocalization between the GABA vesicular transporter, vGAT and parvalbumin in females, indicating that greater GABA releases from local interneurons in this sex may be a compensatory response to lower levels of perisomatic innervation by PV+ interneurons. Consistent with this, there were no sex differences related to spontaneous GABAergic synaptic events although CIE/WD decreased their frequency specifically in BLABNST neurons from both sexes. Altogether, these findings demonstrate that CIE/WD dynamically alters GABAergic function in an input-, sex- and population-specific fashion. Moreover, there are basal sex differences in both the anatomy of BLA GABAergic synapses and their function.
期刊介绍:
Addiction Biology is focused on neuroscience contributions and it aims to advance our understanding of the action of drugs of abuse and addictive processes. Papers are accepted in both animal experimentation or clinical research. The content is geared towards behavioral, molecular, genetic, biochemical, neuro-biological and pharmacology aspects of these fields.
Addiction Biology includes peer-reviewed original research reports and reviews.
Addiction Biology is published on behalf of the Society for the Study of Addiction to Alcohol and other Drugs (SSA). Members of the Society for the Study of Addiction receive the Journal as part of their annual membership subscription.