Scientific Goal

In our daily conversations, we rely on our brains’ ability to recognize individual sound objects, such as consonants and syllables. However, we know little about how our brains integrate spectrally and temporally distributed sounds to extract these features. In our lab, we use mouse as a model system to delineate the circuit mechanisms underlying vocal communications. Intriguingly, even mice use vocalizations to initiate social behaviors; attraction to counter-sex calls, avoidance of pain vocalizations, and maternal response to pup isolation calls are well-known examples. This simple repertoire of behaviors, as well as their simply organized auditory cortex, makes mice an ideal model system for elucidating the circuits underlying vocal communication. By combining our expertise in whole-cell recording, two-photon imaging, and behaviors, we are uniquely poised to build a bridge between our understanding on vocal processing at synaptic, circuitry, and behavioral levels.

In addition to the contribution to basic science, these experiments will shed light on the misregulation of cortical circuits in diseased brains. In collaboration with researchers at the UNC Neuroscience Center and Department of Psychiatry, we use mouse models of psychiatric disorders, such as autism spectrum disorders, to determine how circuit alteration leads to disturbed social communications in these disorders.

Techniques

In vivo whole-cell recording

Excitation and inhibition are inseparable events in neuronal circuits. 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 toward complex sounds. (Ref: Kato et al., Neuron 2017; Aponte et al., Nat Commun 2021)

Optogenetics during in vivo single-unit recording

Precise orchestration of excitatory and inhibitory neuronal subtypes plays crucial roles in the processing of sensory information. Toward understanding of the roles of neuronal subtypes, we perform subtype-specific optogenetics during in vivo electrophysiology. These experiments 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. (Ref: Kato et al., Neuron 2015; Aponte et al., Nat Commun 2021)

Two-photon calcium imaging

Sensory information is encoded in the activity of large ensemble of neurons. In vivo two-photon calcium imaging allows simultaneous measurement of activity from hundreds of neurons, thus providing us with a great statistical power to understand the information coding strategy in the brain. Taking advantage of chronic window implantation technique, we track the auditory cortex ensemble activity for weeks of period and investigate how information encoding changes during the course of learning and behavioral experiences. (Ref: Kato et al., Neuron 2012, 2013, 2015, 2017; Gillett et al., Front Neural Circuits 2018)

Macroscopic imaging across the entire auditory cortices

In humans, sounds are encoded in as many as 15 cortical areas which are interconnected to form hierarchical processing streams. However, it has been largely unknown how higher auditory cortices synthesize the inputs from primary areas to extract complex sound features. Mouse auditory system, with its compact organization, offers us a unique opportunity to simultaneously measure activity from all five cortical areas using macroscopic imaging. Using this technique, we aim to understand the hierarchical interaction between primary and secondary cortices, with the goal of understanding the general principle of inter-areal interaction.

Assessment of perceptual behaviors

A fundamental challenge in neuroscience is to understand how our brains translate sensory inputs into behavioral outputs. The auditory cortex as a whole is indispensable for various innate and learned behaviors towards complex sounds, such as vocal communications. However, little is known regarding the specialized roles of individual cortical areas in behaviors. We assess sound-guided behaviors in head-fixed mice while simultaneously applying other circuit dissection techniques, including optogenetics and two-photon calcium imaging. With this approach, we aim to determine perceptual roles of auditory cortical circuitry. (Ref: Kato et al., Neuron 2015)

Mouse models for psychiatric disorders

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. By applying circuit dissection techniques to ASD mouse models, we will investigate how auditory cortical circuits are disturbed in autistic brains. The circuit-level knowledge 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.