scholarly journals Withdrawal from Chronic Ethanol Exposure Increases Postsynaptic Glutamate Function of Insular Cortex Projections to the Rat Basolateral Amygdala

2019 ◽  
Author(s):  
Molly M. McGinnis ◽  
Brian C. Parrish ◽  
Brian A. McCool
Keyword(s):  
Synaptic Plasticity ◽  
Negative Affect ◽  
Basolateral Amygdala ◽  
Glutamate Release ◽  
Insular Cortex ◽  
Ethanol Exposure ◽  
Ethanol Withdrawal ◽  
Chronic Ethanol ◽  
Chronic Ethanol Exposure ◽  
Chronic Intermittent Ethanol

AbstractA key feature of alcohol use disorder (AUD) is negative affect during withdrawal, which often contributes to relapse and is thought to be caused by altered brain function, especially in circuits that are important mediators of emotional behaviors. Both the agranular insular cortex (AIC) and the basolateral amygdala (BLA) regulate emotions and are sensitive to ethanol-induced changes in synaptic plasticity. The AIC and BLA are reciprocally connected, however, and the effects of chronic ethanol exposure on this circuit have yet to be explored. Here, we use a combination of optogenetics and electrophysiology to examine the pre- and postsynaptic changes that occur to AIC – BLA synapses following withdrawal from 7- or 10-days of chronic intermittent ethanol (CIE) exposure. While CIE/withdrawal did not alter presynaptic glutamate release probably from AIC inputs, withdrawal from 10, but not 7, days of CIE increased AMPA receptor-mediated postsynaptic function at these synapses. Additionally, NMDA receptor-mediated currents evoked by electrical stimulation of the external capsule, which contains AIC afferents, were also increased during withdrawal. Notably, a single subanesthetic dose of ketamine administered at the onset of withdrawal prevented the withdrawal-induced increases in both AMPAR and NMDAR postsynaptic function. Ketamine also prevented the withdrawal-induced increases in anxiety-like behavior measured using the elevated zero maze. Together, these findings suggest that chronic ethanol exposure increases postsynaptic function within the AIC – BLA circuit and that ketamine can prevent ethanol withdrawal-induced alterations in synaptic plasticity and negative affect.

scholarly journals Chronic Ethanol Differentially Modulates Glutamate Release from Dorsal and Ventral Prefrontal Cortical Inputs onto Rat Basolateral Amygdala Principal Neurons

2019 ◽  
Author(s):  
Molly M. McGinnis ◽  
Brian C. Parrish ◽  
Ann M. Chappell ◽  
Brian A. McCool
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Basolateral Amygdala ◽  
Glutamate Release ◽  
Ethanol Exposure ◽  
Chronic Ethanol ◽  
Sprague Dawley ◽  
Behavioral Alterations ◽  
Release Probability ◽  
Chronic Ethanol Exposure

AbstractThe medial prefrontal cortex (mPFC) and the basolateral amygdala (BLA) have strong reciprocal connectivity. Projections from the BLA to the mPFC can bidirectionally modulate anxiety-related behaviors but it is unclear if the same is true for mPFC to BLA projections. Our laboratory is specifically interested in withdrawal-related anxiety-like behavior and the underlying synaptic plasticity. Here, we use optogenetics and chemogenetics to characterize the neurophysiological and behavioral alterations produced by chronic ethanol exposure and withdrawal on dorsal mPFC/prelimbic (dmPFC/PL) and ventral mPFC (vmPFC/IL) terminals in the BLA. We exposed adult male Sprague-Dawley rats to chronic intermittent ethanol (CIE) using vapor chambers, measured anxiety-like behavior on the elevated zero maze (EZM), and used electrophysiology to record glutamatergic and GABAergic responses in BLA principal neurons. We found that 24-hour withdrawal following a 7-day CIE exposure significantly increased the glutamate release probability from PL/dmPFC terminals, but significantly decreases the glutamate release probability from IL/vmPFC terminals. Chemogenetic inhibition of PL/dmPFC terminals in the BLA attenuated the increased withdrawal-dependent, anxiety-like behavior. These data demonstrate that chronic ethanol exposure and withdrawal strengthens the PL/dmPFC – BLA pathway but weakens the IL/vmPFC – BLA pathway. Moreover, we provide novel evidence that the PL/dmPFC – BLA pathway can modulate anxiety-like behavior. These findings suggest that mPFC-BLA circuits known to regulate the acquisition of aversive behaviors are up-regulated by chronic ethanol while those involved with the extinction of these behaviors are down-regulated.Significance StatementAccumulating evidence suggests that the medial prefrontal cortex and its projections to the basolateral amygdala bidirectionally modulate fear-related behaviors. Since the neuronal circuits for fear and anxiety are thought to overlap, we sought to examine the role of prelimbic and infralimbic subdivisions of the medial prefrontal cortex and their inputs to the basolateral amygdala in regulating anxiety. Specifically, we focused on alcohol withdrawal-induced anxiety-like behavior, which is a commonly reported cause of relapse in human alcoholics. In our study, we used optogenetics and chemogenetics to demonstrate, for the first time, that withdrawal from chronic ethanol exposure strengthens prelimbic synapses, but weakens infralimbic synapses in the basolateral amygdala and that inhibiting glutamate release from prelimbic terminal in the basolateral amygdala reduces anxiety-like behavior.

Neuroprotective effects of soy isoflavones on chronic ethanol-induced dementia in male ICR mice

2020 ◽  
Vol 11 (11) ◽  
pp. 10011-10021
Author(s):  
Cong Lu ◽  
Rongjing Gao ◽  
Jingwei Lv ◽  
Ying Chen ◽  
Shuying Li ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Cognitive Deficit ◽  
Ethanol Exposure ◽  
Soy Isoflavones ◽  
Chronic Ethanol ◽  
Neuroprotective Effects ◽  
Cholinergic Function ◽  
Chronic Ethanol Exposure ◽  
Neuron Apoptosis

Chronic ethanol intake can lead to cognitive deficit by reducing cholinergic function, inhibiting synaptic plasticity and causing neuron apoptosis. Soy isoflavones effectively improved the cognitive impairment induced by chronic ethanol exposure.

scholarly journals Interaction Between Social Defeat Stress and Chronic Ethanol Exposure on Behaviors During Ethanol Withdrawal and Pro-Inflammatory Cytokines in Mice

2021 ◽  
Vol 2 ◽  
pp. 1-11
Author(s):  
Gessynger Morais-Silva ◽  
Pedro B. Portilho ◽  
Juliana Fernandes-Santos ◽  
Rafaella M. Queiroz ◽  
Simone R. Deconte ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Social Defeat ◽  
Ethanol Exposure ◽  
Ethanol Withdrawal ◽  
Chronic Ethanol ◽  
Social Defeat Stress ◽  
Chronic Ethanol Exposure ◽  
Pro Inflammatory Cytokines

Alterations of Rat Corticostriatal Synaptic Plasticity After Chronic Ethanol Exposure and Withdrawal

2006 ◽  
Vol 30 (5) ◽  
pp. 819-824 ◽  
Author(s):  
Jian Xun Xia ◽  
Jing Li ◽  
Rong Zhou ◽  
Xiao Hu Zhang ◽  
Yin Bing Ge ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Ethanol Exposure ◽  
Chronic Ethanol ◽  
Chronic Ethanol Exposure

scholarly journals Chronic intermittent ethanol exposure selectively increases synaptic excitability in the ventral domain of the rat hippocampus

2018 ◽  
Author(s):  
Sarah E. Ewin ◽  
James W. Morgan ◽  
Farr Niere ◽  
Nate P. McMullen ◽  
Samuel H. Barth ◽  
...  
Keyword(s):  
Affective State ◽  
Ethanol Exposure ◽  
Chronic Ethanol ◽  
Spatial Learning And Memory ◽  
List Type ◽  
Chronic Ethanol Exposure ◽  
Ca1 Region ◽  
Chronic Intermittent Ethanol ◽  
Long Evans ◽  
Chronic Intermittent Ethanol Exposure

AbstractMany studies have implicated hippocampal dysregulation in the pathophysiology of alcohol use disorder (AUD). However, over the past twenty years, a growing body of evidence has revealed distinct functional roles of the dorsal (dHC) and ventral (vHC) hippocampal subregions, with the dHC being primarily involved in spatial learning and memory and the vHC regulating anxiety-and depressive-like behaviors. Notably, to our knowledge, no rodent studies have examined the effects of chronic ethanol exposure on synaptic transmission along the dorsal/ventral axis. To that end, we examined the effects of the chronic intermittent ethanol vapor exposure (CIE) model of AUD on dHC and vHC synaptic excitability. Adult male Long-Evans rats were exposed to CIE or air for 10 days (12 hrs/day; targeting blood ethanol levels of 175-225 mg%) and recordings were made 24 hours into withdrawal. As expected, this protocol increased anxiety-like behaviors on the elevated plus-maze. Extracellular recordings revealed marked CIE-associated increases in synaptic excitation in the CA1 region that were exclusively restricted to the ventral domain of the hippocampus. Western blot analysis of synaptoneurosomal fractions revealed that the expression of two proteins that regulate synaptic strength, GluA2 and SK2, was dysregulated in the vHC, but not the dHC, following CIE. Together, these findings suggest that the ventral CA1 region may be particularly sensitive to the maladaptive effects of chronic ethanol exposure and provide new insight into some of the neural substrates that may contribute to the negative affective state that develops during withdrawal.HighlightsChronic intermittent ethanol exposure produces robust increases in anxiety-like behavior in male Long Evans rats.Chronic intermittent ethanol exposure increases synaptic excitability in the ventral, but not the dorsal, domain of the hippocampus.These changes in excitability are associated with alterations in synaptoneurosomal expression of small conductance calcium-activated potassium channels and the GluA2 AMPA receptor subunit that are also restricted to the ventral hippocampus.

scholarly journals Polymodal Sensory Thalamic Inputs to the Rat Lateral Amygdala are Facilitated by Chronic Ethanol Exposure and Regulate Withdrawal-associated Anxiety

2019 ◽  
Author(s):  
Melissa Morales ◽  
Molly M. McGinnis ◽  
Ann M. Chappell ◽  
Brian C. Parrish ◽  
Brian A. McCool
Keyword(s):  
Glutamate Release ◽  
Ethanol Exposure ◽  
Synaptic Function ◽  
Chronic Ethanol ◽  
Thalamic Nuclei ◽  
Lateral Amygdala ◽  
Systemic Injection ◽  
Chronic Ethanol Exposure ◽  
Thalamic Projections

AbstractThalamic projections to the lateral amygdala regulate the acquisition of conditioned aversive and reward-related behaviors. Recent work suggests that exposure to chronic ethanol up-regulates presynaptic function of lateral amygdala stria terminalis inputs which contain projections from somatosensory thalamic nuclei. To understand potential contributions by thalamic inputs and their role in the expression of withdrawal-associated aversive behaviors, we integrated optogenetic and chemogenetic approaches with in vitro measures of synaptic function and anxiety-like behavior. We found that expression of Channelrhodopsin in the caudal extension of the posterior thalamic group (cPO) produced monosynaptic glutamatergic synaptic responses in lateral amygdala principal neurons that could be inhibited by co-expression of the hM4-Gi-DREADD. Chronic ethanol exposure increased glutamate release from these cPO terminals but did not impact inhibition by the DREADD agonist, CNO. Systemic injection of CNO specifically reduced withdrawal-related increases in anxiety-like behaviors in animals expressing the Gi-DREADD in cPO. And, microinjection of CNO directly into the lateral amygdala mimicked this anti-anxiety effect. These findings suggest that the cPO-LA circuit is vulnerable to chronic ethanol exposure and plays an important role in regulating anxiety-like behavior following chronic ethanol exposure.

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