Periodic Reporting for period 4 - CLAUSTRUM (The Claustrum: A Circuit Hub for Attention)
Reporting period: 2022-09-01 to 2024-02-29
Our ERC-funded research aimed to decipher the function of the claustrum, an intriguing and enigmatic brain structure.
To pay attention, our brain needs to constantly perform two complementary tasks: 1) Highlight relevant information & 2) Tune out information that is irrelevant. This fundamental function of the brain is disrupted in a large proportion of the population that is suffering from Attention Deficit Disorders (ADD), and is therefore of high relevance for society. Furthermore, drug addiction involves increased attention to drug-associated cues, a process termed 'incentive salience', whereby the drive to consume drugs is triggered by people, location, and paraphernalia previously associated with the drug.
Our work has uncovered significant mechanistic insight into how the claustrum supports aspects of attention relevant to ADD, such as task engagement (Atlan..Citri 2024) and resilience to distraction (Atlan..Citri 2018). We have also identified the role of the claustrum in incentive salience in the context of cocaine (Terem..Citri 2020), as well as in opioid consumption (Terem..Citri 2023). We have also developed technical innovations relevant to human imaging of the claustrum (Berman..Citri Mezer 2020) and preclinical investigation of opioid addiction (Peretz-Rivlin 2024).
To pay attention, our brain needs to constantly perform two complementary tasks: 1) Highlight relevant information & 2) Tune out information that is irrelevant. This fundamental function of the brain is disrupted in a large proportion of the population that is suffering from Attention Deficit Disorders (ADD), and is therefore of high relevance for society. Furthermore, drug addiction involves increased attention to drug-associated cues, a process termed 'incentive salience', whereby the drive to consume drugs is triggered by people, location, and paraphernalia previously associated with the drug.
Our work has uncovered significant mechanistic insight into how the claustrum supports aspects of attention relevant to ADD, such as task engagement (Atlan..Citri 2024) and resilience to distraction (Atlan..Citri 2018). We have also identified the role of the claustrum in incentive salience in the context of cocaine (Terem..Citri 2020), as well as in opioid consumption (Terem..Citri 2023). We have also developed technical innovations relevant to human imaging of the claustrum (Berman..Citri Mezer 2020) and preclinical investigation of opioid addiction (Peretz-Rivlin 2024).
Our work, funded by ERC CoG CLAUSTRUM, demonstrates that the claustrum plays a central role in these fundamental functions of the brain. Thus, we have identified the role of the claustrum in supporting resilience to distraction (Current Biology 2018), and recently published an extensive study, illustrating that a population of claustrum neurons restrict engagement during sleep and behavior (Nature Communications 2024). Furthermore, the recent Nature Communications publication illustrates a novel approach (the ENGAGE task) for detailed assessment of various aspects of attention in mice. Our investigation of dopamine neuromodulation of the claustrum led to identification of the role of a population of claustrum neurons in mediating contextual association of reward (Current Biology 2020), and a follow-up investigation of the role of the claustrum in controlling opioid self-administration found that thid population of claustrum neurons restricts opioid consumption (Current Biology 2023). This project also led to the development of an automated group-housed oral fentanyl self-administration method in mice, relevant to preclinical drug development (Psychopharmacology 2024). In addition, we developed a novel approach automatic segmentation of the dorsal claustrum in humans using in vivo high-resolution MRI (Cerebral Cortex Communications 2020). In our most recent ERC CoG supported investigation (under development) we are identifying the role of the claustrum in enabling the acquisition of strategies to optimize task performance (in preparation). This project will extend beyond our most ambitious plans when setting out on the ERC project CLAUSTRUM, in terms of the technological challenge involved in performing the project and insight obtained. Identifying how the claustrum is involved in attention and addiction is expected to allow the development of novel diagnostic and therapeutic approaches to deal with the prevalent disturbances found in society in relation to ADD and addiction.
Beyond these formal publications, our work was also broadly disseminated to the scientific community in multiple venues, in talks and poster presentations: FENS 2024, Vienna; EBPS, Mannheim, 2023; U Ottawa, U Toronto, U Western Ontario, McGill, Concordia, 2023, iCARE Jerusalem, 2023, iSFN, Eilat, 2023; MNS Dubrovnik, 2022; SfN 2019, MNS Marrakech 2019, EMBO Ein Gedi 2019; FENS 2018, SfN 2018, SfN 2017, U Brussels 2018, Seville 2018 among others), as well as to the lay audience in the form of a blog presentation (The science breaker), and a paper directed at children (in Frontiers for Young Minds) and presentations to the lay audience (in Paris 2018, London 2019, Jerusalem 2022 and Stockholm 2023). Our work has also been broadly cited by the lay media, across many venues (including radio, TV printed press, and online press).
Beyond these formal publications, our work was also broadly disseminated to the scientific community in multiple venues, in talks and poster presentations: FENS 2024, Vienna; EBPS, Mannheim, 2023; U Ottawa, U Toronto, U Western Ontario, McGill, Concordia, 2023, iCARE Jerusalem, 2023, iSFN, Eilat, 2023; MNS Dubrovnik, 2022; SfN 2019, MNS Marrakech 2019, EMBO Ein Gedi 2019; FENS 2018, SfN 2018, SfN 2017, U Brussels 2018, Seville 2018 among others), as well as to the lay audience in the form of a blog presentation (The science breaker), and a paper directed at children (in Frontiers for Young Minds) and presentations to the lay audience (in Paris 2018, London 2019, Jerusalem 2022 and Stockholm 2023). Our work has also been broadly cited by the lay media, across many venues (including radio, TV printed press, and online press).
We have been defining the forefront of the claustrum field, proposing the working hypotheses that have been accepted by the field, as well as developing the technical approaches that enable investigation of the claustrum. Furthermore, we have extended our work from mice to humans, developing a collaborative effort to segment the claustrum in human MRI data. We anticipate to continue developing these avenues, providing a description of the natural activity patterns of differential claustrum networks, their engagement in attention-demanding tasks, and the impact of their manipulation on mice behavior (and sleep patterns). In addition, we are aiming to identify claustrum-based mechanisms for reducing drug seeking, which we believe could be of high relevance to human health.