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AttentionCircuits Report Summary

Project ID: 335587
Funded under: FP7-IDEAS-ERC
Country: Germany

Mid-Term Report Summary - ATTENTIONCIRCUITS (Modulation of neocortical microcircuits for attention)

The summary should be a stand-alone description of the project and its outcomes. This text should be as concise as possible and suitable for dissemination to non specialist audiences. Please notice that this summary will be published.
At every moment in time, the brain receives a vast amount of sensory information about the environment. This makes attention, the process by which we select currently relevant stimuli for processing and ignore irrelevant input, a fundamentally important brain function. Studies in primates have yielded a detailed description of how attention to a stimulus modifies the responses of neuronal ensembles in visual cortex, but how this modulation is produced mechanistically in the circuit is not well understood. In neocortical circuits, different types of inhibitory interneurons control distinct aspects of the local computations, whereas excitatory projection neurons convey information between brain areas. The central hypothesis motivating our work is that differential modulation of interneuron types is a key mechanism of attention in neocortex.

One prominent source for this type of modulation is different neuromodulators such as acetylcholine and serotonin, which are known to be released in neocortex during attentive behavior. Our results indicate that one type of interneuron that can cause both decreases and increases of inhibition in the local network displays strong and surprisingly rapid responses to acetylcholine in mice. In contrast to predictions based on previous data, however, these cells do not respond to serotonin. Given that one fundamental motivation for our work is to define neuronal mechanisms that also play a role in the human brain, we have investigated the same interneuron type in human tissue from patients that undergo surgical treatment, which revealed very similar responses to acetylcholine and expression of cholinergic receptor types as in the mouse. Together with similarities in other cellular properties, these results indicate that at least for this type of interneuron, investigations in mice have a good potential for applicability to the human brain.

One aspect that makes the dissection of different interneuron types challenging is their prominent interconnectivity in the local circuit. While our previous work along with the results from many other labs indicates that this ‘inhibition of inhibition’ is an important processing motif, it poses technical challenges that can best be overcome by dissecting the circuit into genetically-defined populations of neurons. We have recently identified a novel genetic marker for a type of interneuron that was not previously addressable, and are using this along with other markers at the moment to define the role these cells play during attention. To this end we have developed behavioral paradigms for mice that demand modality-specific attention. In one task, the mice are required to use visual information while ignoring sounds, whereas in a second version a start cue instructs the animals to attend to the visual or auditory domain on a trial-by-trial basis. In contrast to previous data from projection neurons, our results indicate that different interneuron types are strongly modulated by different aspects of the tasks, such as anticipation, sensory processing and reward consumption. In parallel, optogenetic activity manipulations will reveal for which aspects of the behavior these activity patterns are required. These results offer a first mechanistic understanding of attention, which also provides a basis for development of rational therapeutic strategies for attention disorders. Beyond attention, selection of different functional states of the same hard-wired circuit by modulatory input is a fundamental, but poorly understood, phenomenon in the brain, and we expect that our insights will elucidate similar mechanisms in other brain areas and functional contexts.

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