scholarly journals A whole-brain imaging-based systems approach to understand origin of addiction in binge-like drinking model

2021 ◽  
Author(s):  
Marzena Stefaniuk ◽  
Monika Pawłowska ◽  
Klaudia Nowicka ◽  
Marcin Barański ◽  
Zbigniew Zielinski ◽  
...  

AbstractMany fundamental questions on addiction development are still unanswered. These questions are frequently difficult to address by examining a single brain structure, but can best be addressed at the systems level. Neurons create functional networks that change over time, since brain regions may work together differently in different contexts. We offer a framework for describing the nature behind alcohol binge drinking and the transition to addiction. The present study investigated whole-brain c-Fos expression following reexposure to alcohol in a model of binge-like drinking in mice in IntelliCage. We developed a dedicated image computational workflow to identify c-Fos-positive cells in three-dimensional images obtained after optical tissue clearing and whole-brain imaging in the light-sheet microscope. We analyzed functional networks and brain modularity following reexposure to alcohol. c-Fos levels in brains from animals that were reexposed to alcohol were clearly different from binge drinking animals. Structures involved in reward processing, decision making and characteristic for addictive behaviors stood out particularly. In alcohol reexposed animals differently active structures either gained or lost correlation when compared to the control group.

2012 ◽  
Vol 107 (10) ◽  
pp. 2853-2865 ◽  
Author(s):  
Ji-Wei He ◽  
Fenghua Tian ◽  
Hanli Liu ◽  
Yuan Bo Peng

While near-infrared (NIR) spectroscopy has been increasingly used to detect stimulated brain activities with an advantage of dissociating regional oxy- and deoxyhemoglobin concentrations simultaneously, it has not been utilized much in pain research. Here, we investigated and demonstrated the feasibility of using this technique to obtain whole brain hemodynamics in rats and speculated on the functional relevance of the NIR-based hemodynamic signals during pain processing. NIR signals were emitted and collected using a 26-optodes array on rat's dorsal skull surface after the removal of skin. Following the subcutaneous injection of formalin (50 μl, 3%) into a hindpaw, several isolable brain regions showed hemodynamic changes, including the anterior cingulate cortex, primary/secondary somatosensory cortexes, thalamus, and periaqueductal gray ( n = 6). Time courses of hemodynamic changes in respective regions matched with the well-documented biphasic excitatory response. Surprisingly, an atypical pattern (i.e., a decrease in oxyhemoglobin concentration with a concomitant increase in deoxyhemoglobin concentration) was seen in phase II. In a separate group of rats with innocuous brush and noxious pinch of the same area ( n = 11), results confirmed that the atypical pattern occurred more likely in the presence of nociception than nonpainful stimulation, suggesting it as a physiological substrate when the brain processes pain. In conclusion, the NIR whole brain imaging provides a useful alternative to study pain in vivo using small-animal models. Our results support the notion that neurovascular response patterns depend on stimuli, bringing attention to the interpretation of vascular-based neuroimaging data in studies of pain.


2021 ◽  
Vol 15 ◽  
Author(s):  
Torben Noto ◽  
Guangyu Zhou ◽  
Qiaohan Yang ◽  
Gregory Lane ◽  
Christina Zelano

Three subregions of the amygdala receive monosynaptic projections from the olfactory bulb, making them part of the primary olfactory cortex. These primary olfactory areas are located at the anterior-medial aspect of the amygdala and include the medial amygdala (MeA), cortical amygdala (CoA), and the periamygdaloid complex (PAC). The vast majority of research on the amygdala has focused on the larger basolateral and basomedial subregions, which are known to be involved in implicit learning, threat responses, and emotion. Fewer studies have focused on the MeA, CoA, and PAC, with most conducted in rodents. Therefore, our understanding of the functions of these amygdala subregions is limited, particularly in humans. Here, we first conducted a review of existing literature on the MeA, CoA, and PAC. We then used resting-state fMRI and unbiased k-means clustering techniques to show that the anatomical boundaries of human MeA, CoA, and PAC accurately parcellate based on their whole-brain resting connectivity patterns alone, suggesting that their functional networks are distinct, relative both to each other and to the amygdala subregions that do not receive input from the olfactory bulb. Finally, considering that distinct functional networks are suggestive of distinct functions, we examined the whole-brain resting network of each subregion and speculated on potential roles that each region may play in olfactory processing. Based on these analyses, we speculate that the MeA could potentially be involved in the generation of rapid motor responses to olfactory stimuli (including fight/flight), particularly in approach/avoid contexts. The CoA could potentially be involved in olfactory-related reward processing, including learning and memory of approach/avoid responses. The PAC could potentially be involved in the multisensory integration of olfactory information with other sensory systems. These speculations can be used to form the basis of future studies aimed at clarifying the olfactory functions of these under-studied primary olfactory areas.


2015 ◽  
Vol 6 (5) ◽  
pp. 1797 ◽  
Author(s):  
Zhe Yang ◽  
Li Mei ◽  
Fei Xia ◽  
Qingming Luo ◽  
Ling Fu ◽  
...  

Author(s):  
Monika Pawłowska ◽  
Marzena Stefaniuk ◽  
Diana Legutko ◽  
Leszek Kaczmarek

Author(s):  
Marie Caroline Müllenbroich ◽  
Ludovico Silvestri ◽  
Lapo Turrini ◽  
Antonino Paolo Di Giovanna ◽  
Tommaso Alterini ◽  
...  

2018 ◽  
Author(s):  
Adam Kimbrough ◽  
Daniel J. Lurie ◽  
Andres Collazo ◽  
Max Kreifeldt ◽  
Harpreet Sidhu ◽  
...  

SummaryThree main theories of the neurobiology of addiction have been proposed: (1) incentive salience mediated by a brainstem-striatal network, (2) habit mediated by a cortico-striato-thalamic network, and (3) hedonic allostasis mediated by an extended amygdala network. Efforts have been made to reconcile these theories within a three-stage model, but the relevance of each theory remains controversial. We tested the validity of each theory with a single dataset using unbiased single-cell whole-brain imaging and data-driven analyses of neuronal activity in a mouse model of alcohol use disorder. Abstinence in alcohol dependent mice decreased brain modularity and resulted in clustering of brain regions that correspond to each stage of the three-stage theory of addiction. Furthermore, we identified several brain regions whose activity highly predicted addiction-like behaviors and “hub” regions that may drive neural activation during abstinence. These results validate the three-stage theory of addiction and identify potential target regions for future study.


2021 ◽  
Author(s):  
Giuseppe de Vito ◽  
Lapo Turrini ◽  
Marie-Caroline Muellenbroich ◽  
pietro ricci ◽  
Giuseppe Sancataldo ◽  
...  

2021 ◽  
Vol 15 ◽  
Author(s):  
Zhouzhou Zhang ◽  
Xiao Yao ◽  
Xinxin Yin ◽  
Zhangcan Ding ◽  
Tianyi Huang ◽  
...  

Whole-brain imaging has become an increasingly important approach to investigate neural structures, such as somata distribution, dendritic morphology, and axonal projection patterns. Different structures require whole-brain imaging at different resolutions. Thus, it is highly desirable to perform whole-brain imaging at multiple scales. Imaging a complete mammalian brain at synaptic resolution is especially challenging, as it requires continuous imaging from days to weeks because of the large number of voxels to sample, and it is difficult to acquire a constant quality of imaging because of light scattering during in toto imaging. Here, we reveal that light-sheet microscopy has a unique advantage over wide-field microscopy in multi-scale imaging because of its decoupling of illumination and detection. Based on this observation, we have developed a multi-scale light-sheet microscope that combines tiling of light-sheet, automatic zooming, periodic sectioning, and tissue expansion to achieve a constant quality of brain-wide imaging from cellular (3 μm × 3 μm × 8 μm) to sub-micron (0.3 μm × 0.3 μm × 1 μm) spatial resolution rapidly (all within a few hours). We demonstrated the strength of the system by testing it using mouse brains prepared using different clearing approaches. We were able to track electrode tracks as well as axonal projections at sub-micron resolution to trace the full morphology of single medial prefrontal cortex (mPFC) neurons that have remarkable diversity in long-range projections.


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