Understanding information flow through the highly complex circuits of interconnected brain cells is quite challenging. Technological advances have enabled tremendous progress over the years. With the support of the Marie Skłodowska-Curie Actions Individual Fellowships (MSCA IF) programme, CORVISDEC used a high-throughput approach to track thousands of neurons in numerous brain regions in alert behaving mice. Analyses have revealed key perceptual, cognitive and motor aspects of decision-making behaviour.
Two photons are better than one
Calcium is an important signal mediator in the brain, flowing into neurons during neuronal activation. Introducing a protein into neurons that becomes fluorescent when calcium enters facilitates the signal that two-photon imaging captures. Lauren Wool of the Queen Square Institute of Neurology, University College London and MSCA fellow explains: “Unlike conventional microscopy that uses one short-wavelength photon to excite a fluorescent molecule, two-photon imaging delivers two long wavelength photons (in the near-infrared or NIR spectrum). NIR photons do not scatter, photobleach proteins, or damage tissue as much, revealing high resolution brain activity in three dimensions stably over time.” This non-invasive technique enables scientists to image brain activity while a mouse performs a behavioural task. Data were analysed and visualised using the open-source SuiteP software by lab alumni Carsen Stringer and Marius Pachitariu.
Together but separate – or not
CORVISDEC focused on the motor cortex during a behavioural task. The mice observed visual cues on computer screens, had to remember the consequences of their previous actions and make decisive reward-linked movements. Taken together, monitoring neuronal activity in this multifaceted task can begin to show how all this information comes together to subserve decision-making and subsequent movement. It can also reveal if or how cortical activity differs when the mouse performs well relative to when it does not. Research over the years has suggested that distinct regions such as the visual and motor cortices process their own information separately and pass it on to other region(s) where the modalities come together for higher function. Wool states: “One of the most exciting and unexpected findings of CORVISDEC was that brain areas that were thought to be functionally distinct are quite heterogeneous and complex. The motor cortex has a substantial population of neurons that respond to visual stimuli, and we observe lots of movement related responses in visual cortex. We have a way to go until we completely understand how this happens, but the very large amount of data we have collected from many thousands of simultaneously active neurons provides a unique opportunity to investigate this.”
Interconnectivity goes beyond the brain
Together with 21 other labs, Wool’s lab formed the International Brain Laboratory, a global neuroscience collaboration dedicated to understanding brain circuits underlying complex behaviour. Among its goals is the expansion and standardisation of neuroscience methods and the sharing of data collected. “Throughout CORVISDEC, I have been developing policy and governance to support the collaboration. My article about our organisational structure as a roadmap for future collaborations in neuroscience and beyond will be published in the December 2020 issue of Current Opinion in Neurobiology.” As the team continues to publish its results, scientists are publicly sharing all data, analyses and code to further exploit the potential of global collaboration to reveal the brain’s mysteries.
CORVISDEC, brain, neurons, cortex, behaviour, calcium, two-photon imaging, decision making, cortical activity, International Brain Laboratory