CALLAX · What is the role of the axonal connections between the hemispheres in sensory processing?
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-03-01 → 2020-02-29
- EU contribution
- €208,400
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
What is the role of the axonal connections between the hemispheres in sensory processing?
Why does our brain have two hemispheres and what is the role of connections between them? While it is well known that in humans, each hemisphere has functional specializations, we have little mechanistic understanding of how circuits communicate across the corpus callosum that connects the hemispheres. Moreover, the role of these callosal axons, and the information they convey is highly debated. There is a century-old debate among cognitive psychologists and neuroscientists: Do callosal axons have mainly an inhibitory action in the other hemisphere, producing a dominant and a repressed hemisphere; or do these projections faithfully report the activity of one hemisphere to the other, facilitating the cooperation between the two hemispheres? In my proposal I aimed to elucidate if the callosal projections within cortical circuits are either inhibitory or excitatory; and what kind of information is conveyed by these callosal axons. Furthermore, I wanted to test if the lack of callosal information modifies the activity of neurons in the cortical circuit. I used two-photon microscopy and calcium indicators expressed in neurons to study the effects of callosal inputs arriving to a cortical area from the contralateral homotopic brain region. During the calcium imaging sessions mice were performing a behavioral task head-fixed, in which they had to estimate position based on tactile stimuli. Using this high spatial resolution technique, I recorded the activity of cortical pyramidal cells as well as callosal axons. Finally, I used optogenetics to inhibit callosal input specifically and measured how this influenced cortical circuits and behavior. Conclusions of the action: Our results show that callosal axons are derived from excitatory neurons, and not just convey reliably information from one hemisphere to the other, but they also shape the activity of the neuron population in the homotopic brain area. Our study strengthens the hypothesis that homotopic brain regions collaborate with each other, instead of having one dominant and one repressed hemisphere. The combination of state-of-the-art microscopy, novel viral methods and mouse behavior made this project very timely. Recently, more and more human studies uncover evidence that altered corpus callosum morphology associated with autism spectrum disorder and schizophrenia. As both medical conditions develop during childhood or young adulthood, these become a lifelong burden for families, healthcare systems, and societies. Therefore, it is essential to explore the normal functioning of the involved brain structures, as well as to understand the pathogenesis and find new therapies. My findings provide for the first time a mechanistic understanding of the role of the connections between our hemispheres and it may provide a framework for understanding diseases that affect the corpus callosum.
Data: CORDIS, © European Union
Project objective
Why does our brain have two hemispheres and what is the role of connections between them? While it is well known that in humans, each hemisphere has functional specializations, we have little mechanistic understanding of how circuits communicate across the corpus callosum that connects the hemispheres. Moreover, the role of these callosal axons, and the information they convey is highly debated. There are two main hypotheses: One suggests that callosal axons have mainly an inhibitory action in the other hemisphere, while the other suggests that the effect is excitatory. Importantly, this century-old debate among cognitive psychologists and neuroscientists remains to be tested. Here I hypothesize that these views are most likely too simplified. Instead, I propose that the actions of these axons are rather complex, causing sequences of excitation and inhibition. Moreover, I propose that it may be more relevant to study what information is conveyed by the callosal axons. To test this, I will use two-photon microscopy and calcium indicators to study the effects of callosal input on the somatosensory cortex of mice that are trained to perform a tactile discrimination task. The combination of state-of-the-art microscopy, novel viral methods and mouse behavior makes this project very timely. I will monitor the activity of thousands of neurons in a specialized part of the rodent somatosensory cortex, called the barrel cortex, while head-fixed mice perform a whisker-dependent object localization task under the microscope. This high spatial resolution technique also allows monitoring directly the activity of callosal axons. Finally, I will use optogenetics to inhibit callosal input specifically and measure how this influences cortical circuits and behavior. My findings will provide for the first time a mechanistic understanding of the role of the connections between our hemispheres and provide a framework for understanding diseases that affect the corpus callosum.
Original text from CORDIS.
Participants
- UNIVERSITETET I OSLO · OsloCoordinatorNorway
Links
Data: CORDIS, © European Union