Browsing by Subject "Insula"

Now showing 1 - 7 of 7
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    Behavioral indicators of succeeding and failing under higher-challenge compulsion-like alcohol drinking in rat
    (Elsevier, 2020-09-01) Darevsky, David; Hopf, Frederic W.; Psychiatry, School of Medicine
    Intake despite negative consequences (compulsivity) contributes strongly to the harm of alcohol use disorder, making the underlying psychological and circuit mechanisms of great importance. To gain insight into possible underlying action strategies, we compared rat licking microstructure across compulsion-like and non-compulsive conditions. We previously showed that drinking under a moderate-challenge, quinine-alcohol model (Alc-ModQ) shows less variable responding in many measures, suggesting a more automatic strategy to overcome challenge. Here, we reanalyzed our original data, newly focusing on the behavioral profile of higher-challenge intake (100 mg/L quinine in alcohol, Alc-HighQ). Alc-HighQ greatly dropped consumption, yet retained aspects of greater automaticity and drive seen with Alc-ModQ, including earlier bout initiation and measures suggesting more stereotyped tongue control. In contrast, Alc-HighQ disordered bout generation and timing. Importantly, only fast-starting bouts persisted under Alc-HighQ, and while there were many fewer longer Alc-HighQ bouts, they still contributed >50 % of consumption. Also, longer bouts under Alc-HighQ had an early, several-second period with greater chance of stopping, but afterwards showed similar persistence and recovery from slow licking as other drinking conditions. Together, our findings elucidate novel behavioral indicators of successful and unsuccessful epochs of Alc-HighQ, compulsion-like intake. We also relate findings to congruent human and animal work implicating anterior insula and medial prefrontal cortices as critical for compulsion-like alcohol responding, and where ventral frontal cortex has been more associated with overall action plan and tongue control (retained under Alc-HighQ), with medial cortex more related to proximal action timing (disrupted under Alc-HighQ except after faster bout initiation).
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    Converging Effects of Chronic Pain and Binge Alcohol Consumption on Anterior Insular Cortex Neurons Projecting to the Dorsolateral Striatum in Male Mice
    (Society for Neuroscience, 2024-04-17) Yin, Yuexi; Haggerty, David L.; Zhou, Shudi; Atwood, Brady K.; Sheets, Patrick L.; Pharmacology and Toxicology, School of Medicine
    Chronic pain and alcohol use disorder (AUD) are highly comorbid, and patients with chronic pain are more likely to meet the criteria for AUD. Evidence suggests that both conditions alter similar brain pathways, yet this relationship remains poorly understood. Prior work shows that the anterior insular cortex (AIC) is involved in both chronic pain and AUD. However, circuit-specific changes elicited by the combination of pain and alcohol use remain understudied. The goal of this work was to elucidate the converging effects of binge alcohol consumption and chronic pain on AIC neurons that send projections to the dorsolateral striatum (DLS). Here, we used the Drinking-in-the-Dark (DID) paradigm to model binge-like alcohol drinking in mice that underwent spared nerve injury (SNI), after which whole-cell patch-clamp electrophysiological recordings were performed in acute brain slices to measure intrinsic and synaptic properties of AIC→DLS neurons. In male, but not female, mice, we found that SNI mice with no prior alcohol exposure consumed less alcohol compared with sham mice. Electrophysiological analyses showed that AIC→DLS neurons from SNI-alcohol male mice displayed increased neuronal excitability and increased frequency of miniature excitatory postsynaptic currents. However, mice exposed to alcohol prior to SNI consumed similar amounts of alcohol compared with sham mice following SNI. Together, our data suggest that the interaction of chronic pain and alcohol drinking have a direct effect on both intrinsic excitability and synaptic transmission onto AIC→DLS neurons in mice, which may be critical in understanding how chronic pain alters motivated behaviors associated with alcohol.
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    Etiology, triggers and neurochemical circuits associated with unexpected, expected, and laboratory-induced panic attacks
    (Elsevier, 2014-10) Johnson, Philip L.; Federici, Lauren M.; Shekhar, Anantha; Department of Psychiatry, IU School of Medicine
    Panic disorder (PD) is a severe anxiety disorder that is characterized by recurrent panic attacks (PA), which can be unexpected (uPA, i.e., no clear identifiable trigger) or expected (ePA). Panic typically involves an abrupt feeling of catastrophic fear or distress accompanied by physiological symptoms such as palpitations, racing heart, thermal sensations, and sweating. Recurrent uPA and ePA can also lead to agoraphobia, where subjects with PD avoid situations that were associated with PA. Here we will review recent developments in our understanding of PD, which includes discussions on: symptoms and signs associated with uPA and ePAs; Diagnosis of PD and the new DSM-V; biological etiology such as heritability and gene×environment and gene×hormonal development interactions; comparisons between laboratory and naturally occurring uPAs and ePAs; neurochemical systems that are associated with clinical PAs (e.g. gene associations; targets for triggering or treating PAs), adaptive fear and panic response concepts in the context of new NIH RDoc approach; and finally strengths and weaknesses of translational animal models of adaptive and pathological panic states.
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    Sex-dependent, lateralized engagement of anterior insular cortex inputs to the dorsolateral striatum in binge alcohol drinking
    (eLife Sciences, 2024-08-28) Haggerty, David L.; Atwood, Brady K.; Pharmacology and Toxicology, School of Medicine
    How does alcohol consumption alter synaptic transmission across time, and do these alcohol-induced neuroadaptations occur similarly in both male and female mice? Previously we identified that anterior insular cortex (AIC) projections to the dorsolateral striatum (DLS) are uniquely sensitive to alcohol-induced neuroadaptations in male, but not female mice, and play a role in governing binge alcohol consumption in male mice (Haggerty et al., 2022). Here, by using high-resolution behavior data paired with in-vivo fiber photometry, we show how similar levels of alcohol intake are achieved via different behavioral strategies across sexes, and how inter-drinking session thirst states predict future alcohol intakes in females, but not males. Furthermore, we show how presynaptic calcium activity recorded from AIC synaptic inputs in the DLS across 3 weeks of water consumption followed by 3 weeks of binge alcohol consumption changes across, fluid, time, sex, and brain circuit lateralization. By time-locking presynaptic calcium activity from AIC inputs to the DLS to peri-initiation of drinking events we also show that AIC inputs into the left DLS robustly encode binge alcohol intake behaviors relative to water consumption. These findings suggest a fluid-, sex-, and lateralization-dependent role for the engagement of AIC inputs into the DLS that encode binge alcohol consumption behaviors and further contextualize alcohol-induced neuroadaptations at AIC inputs to the DLS.
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    Smaller Regional Brain Volumes Predict Posttraumatic Stress Disorder at 3 Months after Mild Traumatic Brain Injury
    (Elsevier, 2021) Stein, Murray B.; Yuh, Esther; Jain, Sonia; Okonkwo, David O.; Mac Donald, Christine L.; Levin, Harvey; Giacino, Joseph T.; Dikmen, Sureyya; Vassar, Mary J.; Diaz-Arrastia, Ramon; Robertson, Claudia S.; Nelson, Lindsay D.; McCrea, Michael; Sun, Xiaoying; Temkin, Nancy; Taylor, Sabrina R.; Markowitz, Amy J.; Manley, Geoffrey T.; Mukherjee, Pratik; TRACK-TBI Investigators; Psychiatry, School of Medicine
    Background: Brain volumes in regions such as the hippocampus and amygdala have been associated with risk for the development of posttraumatic stress disorder (PTSD). The objective of this study was to determine whether a set of regional brain volumes, measured by magnetic resonance imaging at 2 weeks following mild traumatic brain injury, were predictive of PTSD at 3 and 6 months after injury. Methods: Using data from TRACK-TBI (Transforming Research and Clinical Knowledge in TBI), we included patients (N = 421) with Glasgow Coma Scale scores 13-15 assessed after evaluation in the emergency department and at 2 weeks, 3 months, and 6 months after injury. Probable PTSD diagnosis (PTSD Checklist for DSM-5 score, ≥33) was the outcome. FreeSurfer 6.0 was used to perform volumetric analysis of three-dimensional T1-weighted magnetic resonance images at 3T obtained 2 weeks post injury. Brain regions selected a priori for volumetric analyses were insula, hippocampus, amygdala, superior frontal cortex, rostral and caudal anterior cingulate, and lateral and medial orbitofrontal cortices. Results: Overall, 77 (18.3%) and 70 (16.6%) patients had probable PTSD at 3 and 6 months. A composite volume derived as the first principal component incorporating 73.8% of the variance in insula, superior frontal cortex, and rostral and caudal cingulate contributed to the prediction of 3-month (but not 6-month) PTSD in multivariable models incorporating other established risk factors. Conclusions: Results, while needing replication, provide support for a brain reserve hypothesis of PTSD and proof of principle for how prediction of at-risk individuals might be accomplished to enhance prognostic accuracy and enrich clinical prevention trials for individuals at the highest risk of PTSD following mild traumatic brain injury.
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    The role of anterior insula-brainstem projections and alpha-1 noradrenergic receptors for compulsion-like and alcohol-only drinking
    (Springer Nature, 2021) De Oliveira Sergio, Thatiane; Lei, Kelly; Kwok, Claudina; Ghotra, Shahbaj; Wegner, Scott A.; Walsh, Margaret; Waal, Jaclyn; Darevsky, David; Hopf, Frederic W.; Psychiatry, School of Medicine
    Compulsion-like alcohol drinking (CLAD), where consumption continues despite negative consequences, is a major obstacle to treating alcohol use disorder. The locus coeruleus area in the brainstem and norepinephrine receptor (NER) signaling in forebrain cortical regions have been implicated in adaptive responding under stress, which is conceptually similar to compulsion-like responding (adaptive responding despite the presence of stress or conflict). Thus, we examined whether anterior insula (aINS)-to-brainstem connections and alpha-1 NERs regulated compulsion-like intake and alcohol-only drinking (AOD). Halorhodopsin inhibition of aINS-brainstem significantly reduced CLAD, with no effect on alcohol-only or saccharin intake, suggesting a specific aINS-brainstem role in aversion-resistant drinking. In contrast, prazosin inhibition of alpha-1 NERs systemically reduced both CLAD and AOD. Similar to systemic inhibition, intra-aINS alpha-1-NER antagonism reduced both CLAD and AOD. Global aINS inhibition with GABAR agonists also strongly reduced both CLAD and AOD, without impacting saccharin intake or locomotion, while aINS inhibition of calcium-permeable AMPARs (with NASPM) reduced CLAD without impacting AOD. Finally, prazosin inhibition of CLAD and AOD was not correlated with each other, systemically or within aINS, suggesting the possibility that different aINS pathways regulate CLAD versus AOD, which will require further study to definitively address. Together, our results provide important new information showing that some aINS pathways (aINS-brainstem and NASPM-sensitive) specifically regulate compulsion-like alcohol consumption, while aINS more generally may contain parallel pathways promoting CLAD versus AOD. These findings also support the importance of the adaptive stress response system for multiple forms of alcohol drinking.
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    The role of anterior insular cortex inputs to dorsolateral striatum in binge alcohol drinking
    (eLife Sciences, 2022-09-13) Haggerty, David L.; Munoz, Braulio; Pennington, Taylor; Di Prisco, Gonzalo Viana; Grecco, Gregory G.; Atwood, Brady K.; Pharmacology and Toxicology, School of Medicine
    How does binge drinking alcohol change synaptic function, and do these changes maintain binge consumption? The anterior insular cortex (AIC) and dorsolateral striatum (DLS) are brain regions implicated in alcohol use disorder. In male, but not female mice, we found that binge drinking alcohol produced glutamatergic synaptic adaptations selective to AIC inputs within the DLS. Photoexciting AIC→DLS circuitry in male mice during binge drinking decreased alcohol, but not water consumption and altered alcohol drinking mechanics. Further, drinking mechanics alone from drinking session data predicted alcohol-related circuit changes. AIC→DLS manipulation did not alter operant, valence, or anxiety-related behaviors. These findings suggest that alcohol-mediated changes at AIC inputs govern behavioral sequences that maintain binge drinking and may serve as a circuit-based biomarker for the development of alcohol use disorder.