Global brain c-Fos profiling reveals major functional brain networks rearrangements after alcohol reexposure

Stefaniuk, Marzena; Pawłowska, Monika; Barański, Marcin; Nowicka, Klaudia; Zieliński, Zbigniew; Bijoch, Łukasz; Legutko, Diana; Majka, Piotr; Bednarek, Sylwia; Jermakow, Natalia; Wójcik, Daniel K.; Kaczmarek, Leszek

doi:10.1016/j.nbd.2023.106006

Cited by 8 publications

(14 citation statements)

References 110 publications

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“…Prior work has also shown that female binge drinking mice display lower correlation strength in most brain regions as compared to water controls (7). In the current study, it was found that alcohol binge drinking increased modularity compared to water consumption, which is similar to previous results (7). Lastly, 16 connector and 17 provincial hubs were uniquely identified which were distributed across 8 of the 9 modules in the female alcohol drinker network, Figure 11B .…”

Section: Discussionmentioning

confidence: 91%

“…Following previous literature (7, 8, 10, 11, 27), the Fos+ Pearson correlations were used to calculate Euclidean distances between brain region pairs. These were calculated separately within sex and group.…”

Section: Discussionmentioning

confidence: 99%

“…Further, this suggests that alcohol dependence results in a less efficient network structure, where more brain regions are recruited to control behavior (8). Other recent work has shown that alcohol re-access following withdrawal leads to increased modularity (7, 9), suggesting that alcohol re-access results in remodeling of brain networks to become more efficient. Additionally, or alternatively, alcohol re-access may serve as a behavioral event capable of recruiting different brain regions as compared to alcohol drinking alone without a withdrawal period (7, 9).…”

Section: Introductionmentioning

confidence: 96%

“…Other recent work has shown that alcohol re-access following withdrawal leads to increased modularity (7, 9), suggesting that alcohol re-access results in remodeling of brain networks to become more efficient. Additionally, or alternatively, alcohol re-access may serve as a behavioral event capable of recruiting different brain regions as compared to alcohol drinking alone without a withdrawal period (7, 9). Together, these studies indicate that the structure of brain networks is altered by the stage of alcohol abuse, which may reflect differences in how efficiently behavior is generated.…”

Section: Introductionmentioning

confidence: 96%

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Sex Differences in Neural Networks Recruited by Frontloaded Binge Alcohol Drinking

Ardinger,

Chen,

Kimbrough

et al. 2024

Preprint

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Frontloading is an alcohol drinking pattern where intake is skewed toward the onset of access. The goal of the current study was to identify brain regions involved in frontloading. Whole brain imaging was performed in 63 C57Bl/6J (32 female and 31 male) mice that underwent 8 days of binge drinking using the drinking-in-the-dark (DID) model. On days 1-7, three hours into the dark cycle, mice received 20% (v/v) alcohol or water for two hours. Intake was measured in 1-minute bins using volumetric sippers, which facilitated analyses of drinking patterns. On day 8 mice were perfused 80 minutes into the DID session and brains were extracted. Brains were then processed to stain for Fos protein using iDISCO+. Following light sheet imaging, ClearMap2.1 was used to register brains to the Allen Brain Atlas and detect Fos+ cells. For brain network analyses, day 8 drinking patterns were used to characterize mice as frontloaders or non-frontloaders using a recently developed change-point analysis. Based on this analysis the groups were female frontloaders (n = 20), female non-frontloaders (n = 2), male frontloaders (n = 13) and male non-frontloaders (n = 8). There were no differences in total alcohol intake in animals that frontloaded versus those that did not. Only two female mice were characterized as non-frontloaders, thus preventing brain network analysis of this group. Functional correlation matrices were calculated for each group from log10 Fos values. Euclidean distances were calculated from these R values and hierarchical clustering was used to determine modules (highly connected groups of brain regions). In males, alcohol access decreased modularity (3 modules in both frontloaders and non-frontloaders) as compared to water drinkers (7 modules). In females, an opposite effect was observed. Alcohol access (9 modules for frontloaders) increased modularity as compared to water drinkers (5 modules). These results suggest sex differences in how alcohol consumption reorganizes the functional architecture of neural networks. Next, key brain regions in each network were identified. Connector hubs, which primarily facilitate communication between modules, and provincial hubs, which facilitate communication within modules, were of specific interest for their important and differing roles. In males, 4 connector hubs and 17 provincial hubs were uniquely identified in frontloaders (i.e., were brain regions that did not have this status in male non-frontloaders or water drinkers). These represented a group of hindbrain regions (e.g., locus coeruleus and the pontine gray) functionally connected to striatal/cortical regions (e.g., cortical amygdalar area) by the paraventricular nucleus of the thalamus. In females, 16 connector and 17 provincial hubs were uniquely identified which were distributed across 8 of the 9 modules in the female frontloader alcohol drinker network. Only one brain region (the nucleus raphe pontis) was a connector hub in both sexes, suggesting that frontloading in males and females may be driven by different brain regions. In conclusion, alcohol consumption led to fewer, but more densely connected, groups of brain regions in males but not females, and recruited different hub brain regions between the sexes. These results suggest that alcohol frontloading leads to a reduction in network efficiency in male mice.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 96%

See 2 more Smart Citations

Sex Differences in Neural Networks Recruited by Frontloaded Binge Alcohol Drinking

Ardinger,

Chen,

Kimbrough

et al. 2024

Preprint

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“…Mice were placed in IntelliCages and underwent cage adaptation for 10 days. Then, they underwent behavioural training consisting of a series of sessions based on the drinking in the dark paradigm (DiDs) 28,29 and sessions with free access to alcohol (FAAs). Briefly, DiDs involved replacing all water bottles with bottles containing 20% ethanol [v/v] for 2.5 h, beginning 2 h into the dark cycle.…”

Section: Behavioural Trainingmentioning

confidence: 99%

Activation of trace amine‐associated receptor 1 (TAAR1) transiently reduces alcohol drinking in socially housed mice

et al. 2023

Self Cite

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Alcohol dependence is characterized by the abnormal release of dopamine in the brain reward-related areas. Trace amine-associated receptor 1 (TAAR1) is a G protein-coupled receptor that negatively regulates dopamine neurotransmission and thus is a promising target in the treatment of drug addiction. However, the role of TAAR1 in the regulation of alcohol abuse remains understudied. Here, we assessed the effect of TAAR1 activation on alcohol drinking behaviours of C57Bl/6J female mice housed in IntelliCages. The animals were administered with either vehicle or TAAR1 full selective agonist, RO5256390, and tested for alcohol consumption, alcohol preference and motivation for alcohol seeking. We found that mice with the highest preference for alcohol (high drinkers) in the RO5256390 group consumed less alcohol and had lower alcohol preference in comparison with high drinkers in the vehicle group, during 20 h of free alcohol access (FAA). We also found decreased alcohol consumption and alcohol preference comparing all animals in the RO5256390 to all animals in the vehicle group, during 20 h of FAA performed after the abstinence. These effects of RO5256390 lasted for the first 24 h after administration that roughly corresponded to the compound level in the brain, measured by mass spectrometry. Finally, we found that administration of RO5256390 may attenuate motivation for alcohol seeking. Taken together, our findings reveal that activation of TAAR1 may transiently reduce alcohol drinking; thus, TAAR1 is a promising target for the treatment of alcohol abuse and relapse.

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descSPIM: an affordable and easy-to-build light-sheet microscope optimized for tissue clearing techniques

Otomo,

Omura,

Nozawa

et al. 2024

Nat Commun

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Despite widespread adoption of tissue clearing techniques in recent years, poor access to suitable light-sheet fluorescence microscopes remains a major obstacle for biomedical end-users. Here, we present descSPIM (desktop-equipped SPIM for cleared specimens), a low-cost ($20,000–50,000), low-expertise (one-day installation by a non-expert), yet practical do-it-yourself light-sheet microscope as a solution for this bottleneck. Even the most fundamental configuration of descSPIM enables multi-color imaging of whole mouse brains and a cancer cell line-derived xenograft tumor mass for the visualization of neurocircuitry, assessment of drug distribution, and pathological examination by false-colored hematoxylin and eosin staining in a three-dimensional manner. Academically open-sourced (https://github.com/dbsb-juntendo/descSPIM), descSPIM allows routine three-dimensional imaging of cleared samples in minutes. Thus, the dissemination of descSPIM will accelerate biomedical discoveries driven by tissue clearing technologies.

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Global brain c-Fos profiling reveals major functional brain networks rearrangements after alcohol reexposure

Cited by 8 publications

References 110 publications

Sex Differences in Neural Networks Recruited by Frontloaded Binge Alcohol Drinking

Sex Differences in Neural Networks Recruited by Frontloaded Binge Alcohol Drinking

Activation of trace amine‐associated receptor 1 (TAAR1) transiently reduces alcohol drinking in socially housed mice

descSPIM: an affordable and easy-to-build light-sheet microscope optimized for tissue clearing techniques

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