Our primary goal is to identify how our brain processes sound inputs to detect complex patterns, such as our vocalizations. We aim to gain holistic understanding of auditory cortical circuits through investigations at multiple scales: namely, synaptic integration in individual neurons, cellular interaction in local circuits, and macroscopic interaction across brain areas. Findings in the simple mouse cortex should provide a first step towards the ultimate understanding of the complex human brain circuits that enable verbal communication, and how they fail in psychiatric disorders.

 
 

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Shaping of sensory tuning by excitation-inhibition interaction

Excitation and inhibition are inseparable events in neuronal circuits. Accumulating evidence has emphasized the critical role of inhibition in shaping the sensory representations in the cortex. However, how inhibitory circuits operate in awake brains has been a matter of discussion, due to the paucity of high-quality in vivo intracellular recording data. We use in vivo whole-cell recordings to measure sound-evoked excitatory and inhibitory synaptic currents in the auditory cortex in awake, head-fixed mice. We aim to elucidate how coordinated action of excitation and inhibition shapes tuning properties of individual neurons, and how they are affected by behavioral states of the animals.

 

Dissection of local circuits using in vivo two-photon calcium imaging

Numerous subtypes of excitatory and inhibitory neurons are fundamental building blocks of the cortical circuits. Precise orchestration of these neuronal subtypes plays crucial roles in the processing of sensory information. Therefore, obtaining the knowledge on the activity patterns of individual neuronal subtypes is essential in the understanding of cortical circuit operation in living brains. Toward this goal, we perform in vivo two-photon calcium imaging to selectively measure the activity from genetically identified neuronal subtypes. Together with subtype-specific optogenetic manipulation techniques, these experiments will allow us to dissect the cortical circuit into its building blocks, and to understand how elementary circuits of neurons control the spatial and temporal structure of sensory representations.

 

Interaction between primary and secondary auditory cortices

In humans, sounds are encoded in as many as 15 cortical areas which are interconnected to form hierarchical processing streams. As the auditory information goes up these hierarchical streams, sound features with greater complexity are extracted, ultimately leading to the processing of human language. However, it has been largely unknown how higher auditory cortices synthesize the inputs from primary areas to extract complex sound features. In our lab, we use the mouse auditory cortex as a model system to understand the hierarchical interaction between primary and secondary cortices, with the goal of understanding the general principle of inter-areal interaction.

 
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Circuits underlying the auditory processing deficits in autism

Disturbed language communication is one of the core symptoms in autism spectrum disorders (ASD). Consistent with this symptom, ASD patients have difficulty processing spectrally and temporally complex auditory inputs. However, little is known regarding the circuit mechanisms underlying how autistic cortices fail to synthesize spectro-temporally distributed sounds to detect complex sound features. By applying above-mentioned circuit dissection techniques to the ASD mouse models, we will investigate how auditory cortical circuits are disturbed in autistic brains. The circuit-level knowledge obtained from these experiments is expected to form a bridge between our understandings of ASD at the genetic and behavioral levels, potentially leading to the development of treatments for the social communication deficits in these disorders.