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Optical interrogation of the claustrum from synapses to behavior

Periodic Reporting for period 2 - CLAUSTRUM (Optical interrogation of the claustrum from synapses to behavior)

Período documentado: 2021-04-01 hasta 2022-09-30

How does the brain integrate inputs from the environment to generate perception and drive decisions? An enigmatic brain region called the claustrum has been suggested to play a role by integrating inputs from multiple brain regions. There is strong interconnectivity between claustrum and nearly every neocortical brain region, indicating that it exerts widespread influence on brain function. However, approaches to specifically record from or manipulate activity in the claustrum have been hindered by the inability to target it selectively. This has been difficult due to the anatomy of the claustrum: it is a long, thin bilateral nucleus buried between the neocortex and the striatum. This proposal aims to understand the role of the claustrum in multisensory integration and behaviour by developing new approaches for monitoring and manipulating the activity of the claustrum. We will harness recent advances in electrophysiological, genetic, optical, and behavioural tools to probe its connectivity, activity, and function in a precise manner. Understanding the role of the claustrum in brain function will provide fundamental insight into information processing in the neocortex, which is a major goal in neuroscience. The claustrum is unique because of its dense reciprocal connectivity with neocortex but nearly complete lack of direct subcortical sensory input. This particular anatomical structure indicates the possibility of a unique function, but none has been observed yet. This proposal will rectify the paucity of data on this distinctive structure by applying a battery of modern tools to address the function of the claustrum. Experiments will address the following key questions:

1. How are claustrocortical inputs integrated and what is the effect of corticoclaustral feedback?

2. What is the activity of claustral neurons during sensory stimulation and motor output?

3. What are the causal relationships between claustrum activity and animal behaviour?
We have compared the developmental and evolutionary origin of the claustrum and subplate (Bruguier et al 2020), assessed how human lesions and animal studies link the claustrum to perception, salience, sleep and pain (Atilgan et al 2022), determined the temporal origin of the claustrum and development of its projections (Hoerder-Suabedissen et al 2022), and found how single neurons and networks in the claustrum integrate input from widespread cortical sources (Shelton et al 2022). We have also contributed to a multifaceted framework of the mouse claustrum complex with European collaborators (Grimstvedt et al 2022) as well as collaborated internationally to perform intravital imaging of the murine subventricular zone with three-photon microscopy (Sun et al 2022).
We have uncovered the major building blocks of the claustrum in mice as well as elucidated its potential roles in humans. We have also determined when the claustrum is active in response to sensory stimuli. By the end of the project, we hope to have a better understanding of the function(s) of the claustrum.