State-dependent and cell-type-specific information processing in auditory cortex

When we are paying attention to music, we can clearly perceive it. When we sleep, however, our perception is significantly diminished. But why? As this simple example, we can perceive exactly same sounds differently depending on our behavioural conditions (e.g., wakefulness vs sleep). But we really don't know exactly how this happens in our brain.

The key is an "internal state" of our brain. Intriguingly, even when we sleep, our brain is still active: our brain is never at rest. But the pattern of brain activity during sleep is different from it in paying attention to sounds. Thus, such "brain states" must be a key to solve the mystery. Our proposed research concerns how our brain processes sounds depending on different brain states.

We will study this at cellular resolution. The neocortex is the brain structure that is highly evolved in the mammals, in particular humans. While millions of neurons are communicating each other, there are many different types of neurons, like our social networks. In the neocortex, neurons form an organised layer structure and in every single layer there are different types of neurons. One of the biggest mysteries in contemporary brain sciences is why they are so diverse. Our proposed research also concerns such neuronal diversity.

Given these two contexts (brain states and neuronal diversity), we will ask how different brain states affect auditory processing in a part of the neocortex, called auditory cortex, and how diverse neurons process sound signals differently. We will address these questions, combining two advanced technologies (called massively parallel neural recording and optogenetics).

Our proposed research will advance our understanding of how we (do not) hear sounds and how the brain works. These efforts will eventually create new opportunities to develop the treatment of hearing disorders and brain diseases.

The laminar structure of the neocortex is one of the most prominent features in the mammalian brain, but its functional significance is still unclear. In addition, cortical states vary from moment to moment, but it is not fully understood how cortical states affect sensory information processing.

In this context, we previously characterised the laminar structure of auditory-evoked and spontaneous population activity in the primary auditory cortex (A1). In addition, we have recently investigated state-dependent and cell-type-specific spontaneous activity in A1. However, the following questions are still unsolved: 1) How does cortical state affect auditory information processing across cortical layers? 2) How is cortical state regulated?

In this project, combining in vivo large-scale electrophysiological recording with optogenetic approaches in rodents, we will address these issues. We will specifically test the hypothesis that cortical states affect auditory processing in a cell-type-specific manner, and that cortical states are regulated by dynamic interplays between neuromodulatory systems and cortical populations. We will focus on the cholinergic nucleus basalis of the basal forebrain (BF) as a model of neuromodulatory systems.

We propose two projects:
In the Project 1, we will comprehensively characterise brain-state-dependent and cell-type-specific auditory processing in A1. We will ask how different cortical states affect auditory processing across layers of A1. We will also ask to what extent cholinergic activity can explain state-dependent information processing in A1.

In the Project 2, we will characterise how neural population in BF functionally interacts with neural population in A1. We will ask how cholinergic activity modulates the laminar structure of population activity in A1.

Our proposed project will shed light on the importance of cortical states in sensory processing and the mechanisms of cortical state regulations.

Our proposed research will benefit fellow neuroscientists. Because we will yield a huge data set regarding state-dependent sensory processing across cortical layers, our database will be very attractive for some of computational neuroscientists. Sharing our data with such researchers, we will maximise an impact of our research on the field of sensory neuroscience, in particular auditory neuroscience.


Our research will contribute to the development of novel neuroprostheses and/or deep brain stimulation because in vivo large-scale extracellular recording is a promising means for neuroprostheses, and because optogenetic approaches are expected as an alternative for electrical deep brain stimulations. Engaging University-wide activities and presenting our research at national and international conferences, we will develop our network with industry to maximise an impact of our research on neurotech industry.


Although our proposal is not directly related to the improvement and restoration of hearing abilities, a better understanding of normal hearing will make an impact on our ageing society in long-term. In short-term, publishing our papers in open-access journals and using online social media including traditional web pages, we will maximise an impact of our research on the general public.

Our in vivo large-scale extracellular recording can also reduce the number of animals to be used for research because it allows us to monitor activity from much more neurons simultaneously compared with conventional techniques. Thus, this proposed research will also contribute to efforts of 3Rs (i.e., reduction).