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Browsing by Subject "Whole-cell patch clamp"
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Item Differential Alterations of Insular Cortex Excitability after Adolescent or Adult Chronic Intermittent Ethanol Administration in Male Rats(Wiley, 2021-02) Luo, Yi-Xiao; Galaj, Ewa; Ma, Yao-Ying; Pharmacology and Toxicology, School of MedicineAdolescent alcohol drinking, primarily in the form of binge-drinking episodes, is a serious public health concern. Binge drinking in laboratory animals has been modeled by a procedure involving chronic intermittent ethanol (CIE) administration, as compared with chronic intermittent water (CIW). The prolonged effects of adolescent binge alcohol exposure in adults, such as high risk of developing alcohol use disorder, are severe but available treatments in the clinic are limited. One reason is the lack of sufficient understanding about the associated neuronal alterations. The involvement of the insular cortex, particularly the anterior agranular insula (AAI), has emerged as a critical region to explain neuronal mechanisms of substance abuse. This study was designed to evaluate the functional output of the AAI by measuring the intrinsic excitability of pyramidal neurons from male rats 2 or 21 days after adolescent or adult CIE treatment. Decreases in intrinsic excitability in AAI pyramidal neurons were detected 21 days, relative to 2 days, after adolescent CIE. Interestingly, the decreased intrinsic excitability in the AAI pyramidal neurons was observed 2 days after adult CIE, compared to adult CIW, but no difference was found between 2 versus 21 days after adult CIE. These data indicate that, although the AAI is influenced within a limited period after adult but not adolescent CIE, neuronal alterations in AAI are affected during the prolonged period of withdrawal from adolescent but not adult CIE. This may explain the prolonged vulnerability to mental disorders of subjects with an alcohol binge history during their adolescent stage.Item Prenatal Alcohol Exposure Reduces Posterior Dorsomedial Striatum Excitability and Motivation in a Sex- and Age-Dependent Fashion(Elsevier, 2020-12) Roselli, Victoria; Guo, Changyong; Huang, Donald; Wen, Di; Zona, Daniel; Liang, Tiebing; Ma, Yao-Ying; Pharmacology and Toxicology, School of MedicinePrenatal alcohol exposure (PAE)-induced clinical symptoms have been widely reported but effective treatments are not yet available due to our limited knowledge of the neuronal mechanisms underlying behavioral outputs. Operant behaviors, including both goal-directed and habitual actions, are essential for everyday life. The dorsomedial striatum (DMS) and the dorsolateral striatum (DLS) have been identified as mediating each type of instrumental behavior, respectively. The current studies were designed to evaluate the effects of PAE (i.e., 3 g/kg, twice a day on gestational days 17-20) on goal-directed vs. habitual behaviors in both females and males during their adolescent and adult stages. We found that PAE-treated adult, but not adolescent, males display similar habitual oral sucrose self-administration but reduced goal-directed sucrose self-administration, compared to those treated by prenatal control (water) exposure (PCE). There were no differences in either habitual or goal-directed sucrose taking between PCE- vs. PAE-treated adolescent and adult females. These results indicate sex- and age-specific effects of PAE on operant behaviors. Further, whole-cell patch clamp recordings showed that the excitability of medium-sized spiny neurons (MSNs) in the posterior DMS (pDMS), but not the anterior DMS (aDMS), was significantly decreased in PAE-treated adult male rats. Notably, chemogenetic enhancement of MSN excitability in the pDMS by the DREADD agonist, compound 21, rescued the motivation of PAE-treated male adult rats. These data suggest that the pDMS may be a key neuronal substrate mediating the PAE-induced low motivation in male adults.