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Title: Functional determinants of spectrotemporal selectivity in mouse auditory cortex
Author: Chapuis, Gaëlle
ISNI:       0000 0004 7658 3388
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2018
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When we interact with our surroundings, our brain must generate a representation of the world that we can interpret and act upon. How such a representation emerges, and how can it best support behavioural needs have been open questions in the field of neuroscience for decades. Throughout the years, theories on sensory processing have often been challenged, owing to new discoveries, which better captured the brain's complex organisation. The mammalian brain possesses a substantial diversity of molecules, cells, and connections, which may serve distinct roles in shaping sensory representation. Such heterogeneity presents a challenge when aiming to study the underlying basis of neural circuit computation and behaviour. Recent technologies have facilitated the functional dissection of brain circuits by enabling us to record and manipulate the activity of distinct cell types based on molecular signatures or anatomical projections. Taking advantage of these technologies, I aimed to decipher the functional determinants of a neuron's selectivity to sound features in the mouse primary auditory cortex (AC), a region of the brain believed to be important for sound perception. Specifically, I studied the principles underlying neural encoding and perception of frequency modulation (FM), an important characteristic of natural sounds such as vocal calls. Using electrophysiological, behavioural and pharmacogenetic techniques in mice, I showed that PV-expressing (PV+) interneurons in AC do not mediate the perception nor the encoding of slow FM direction. Upon the reduction of PV+ interneurons activity in vivo, AC cells remained selective to the direction of FM sounds. Also, mice were able to accurately discriminate the direction of slow FM sounds even when cortical inhibition was reduced. It is proposed that instead, the organisation of ON and OFF receptive fields contributes towards slow FM direction selectivity in cortex. Furthermore, I investigated how sensory processing may adapt to support behavioural needs in scenarios where only a subset of sensory inputs is relevant. By recording in the auditory cortex and thalamus of mice performing auditory tasks, I was able to show that neural responses to sounds adapted according to behavioural demand. Such enhancement in sensory processing appeared as early as in the thalamus, suggesting that this region might be the prime anatomical locus of 'top-down' executive control. Nonetheless, AC neurons displayed complex responses during behaviour, which were highly informative on the animal's behavioural responses. This suggests that the AC encodes high-level aspects of the task alongside representing stimulus features. As the mouse shares a remarkable genetic resemblance and aspects of behaviour with humans, these studies may shed light on auditory processing properties relevant to our species, thereby fostering further translational research between mice and men.
Supervisor: Chadderton, Paul T. Sponsor: Imperial College London
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral