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Probing principles of neural coding with all-optical interrogation in behaving mice

Periodic Reporting for period 1 - NeuralCoding (Probing principles of neural coding with all-optical interrogation in behaving mice)

Reporting period: 2017-09-01 to 2019-08-31

How is behaviourally relevant information encoded in the brain? Sensory neurons transform stimuli from the outside world into electrical signals. These signals are transmitted via the sensory pathway into neocortex, the area crucially involved in higher cognitive functions. Sensory signals then need to be interpreted with respect to the context they have been received in to trigger a meaningful response. The nature of the neural code that is used by neocortical networks to encode information and read-out behaviourally relevant variables is largely unknown. To start to tap into the complex coding of neurons in superficial neocortical layers we need to employ rich behavioural tasks to ensure, that the circuits of interest are engaged in meaningful computations. Due to the heterogeneity of the code we furthermore need to record from as many neurons as possible and apply perturbations to probe the causal relationship between neural codes and behaviour. This powerful combination of cutting-edge techniques will allow us significantly further our understanding of behaviourally-relevant coding in cortex. Every year over a third of the total EU population suffers from mental disorders. The results from this project will give insights into how the brain works through deciphering the neural code. This will strongly increase our handle on treating mental disorders to eventually progress from symptomatic to causal treatments of psychiatric and neurological disorders like schizophrenia, depression and dementia.
To decipher the coding in superficial layers of primary sensory cortex we first developed a behavioural task that optimally engages computations in the circuits of interest and allows meaningful analysis of behaviourally-relevant variables. Then, the activity of hundreds of neurons in superficial primary somatosensory cortex (S1) was recorded simultaneously in mice that learned to perform the two-choice texture discrimination task. When the first contact is made between the texture and the whiskers, a group of neurons that we labelled “touch neurons” increase their firing rate transiently irrespective of the identity of the stimulus. Subsequently, we found that a subgroup of neurons in layer 2/3 (L2/3) S1 are reliably encoding the identity of the stimulus in their firing rate rather than low-level sensory features related to whisker kinematics. Furthermore, around 150 ms after the peak activity of the stimulus-encoding neurons, we found that a different subgroup of neurons present a behaviourally-relevant decision signal within the same circuit in L2/3 S1. Population-wide trajectories are therefore spanning the entirety from the first touch event to the computation of a behaviourally-relevant decision signal within the perceptual decision-making task. We show that the decision signal encoded is not directly driven by lick-related feedback and that it predicts behaviour and learning. These results substantially shift our current understanding of the function of primary somatosensory cortex from an area solely encoding stimulus information to an area directly involved in the decision-making process.
The results have been communicated at three scientific conferences, and the first manuscript will be submitted shortly.
Understanding where and how behaviourally-relevant decision signals are represented in neural circuits is key to unravelling how sensory information is transformed into behavioural output, one of the most fundamental questions in neuroscience. The findings obtained within this action provide conclusive evidence that decision variables relevant for perceptual decision-making are already present at the level of L2/3 S1. This challenges the longstanding idea of physical and conceptual separation of input-related sensory areas and output-related motor areas and will have significant impact on the field of systems neuroscience. These results are likely to be used widely by the scientific community.
The skills acquired during this project, from the building of behavioural setups and microscopes, to supervision and mentorship as well as data analysis are providing an extremely valuable skill set for the next career steps of the researcher. Upon publication of the manuscript the researcher is planning to apply for independent group leader positions in Europe to apply the skills acquired and strengthen scientific excellence in Europe.
Mouse performing the behavioural task (left) and neuronal activity sorted by activity (right).