The human brain is a tremendously complex neuronal circuit that we don’t really understand. For example, we still do not know how sensory information about the world is encoded in neuronal population activity and transformed into a percept.
We investigate how information is encoded in the brain (the “neural code”) and how this code is read out to make decisions and generate percepts. We uncover how sensory experience shapes this code and the underlying neuronal circuits, and how these circuits change with learning and aging. To do this we build, we code, we experiment, and we ponder.
Because of the importance of hearing for human communication, we focus on the auditory system, particularly the auditory cortex as well as the frontal cortex.
Current Projects
How do cortical circuits develop?
It is clear now that we do not come hard-wired but that interaction with the environment plays a major role in shaping our brain. In particular, during early life, sensory experience shapes the refinement of connections in the brain, but after the critical period only limited remodeling (plasticity) is possible. The period during which sensory experience exerts its powerful influence starts in the womb. For example, newborns can recognize their mother’s voice. How does this early experience sculpt the brain? What circuits does experience act on?
One focus of our research is to figure out what circuits and mechanisms allow the cortex to develop and be plastic in early life. We previously identified a specific group of neurons present predominantly in the developing brain, subplate neurons, that play a key role in this process. These neurons are the first to receive inputs from the thalamus and project into the (future) thalamorecipient layer 4. Loss of subplate neurons prevents cortical development. We investigate how these neurons control cortical development, how they are integrated in the developing cortical circuitry, and how their function is disrupted in neurodevelopmental disorders such as autism. We also showed that subplate circuits are sculpted by early sensory experience, making them the earliest cortical substrate of experience-dependent changes.
More information here.
How do cortical circuits compute and adjust to behavioral demands?
The cortex is a laminated structure that is thought to underlie sequential information processing. Thus, we are very interested in the transformation of sound representation between layers and the underlying circuitry. Our work has already identified the functional organization and micro-circuitry of layers 2/3 and 4 of the auditory cortex, and how this architecture can change. We are now tackling the deeper layers and use single-cell optogenetic stimulation to reveal the functional connectivity in vivo.
Attention and task engagement can make important stimuli more salient, but the underlying circuit changes have been unclear. We have shown how responses of neurons and their network properties can rapidly and adaptively be reshaped when an animal is engaged in a behavioral task. We also identified a key role of the orbitofrontal cortex in this process. Using targeted single-cell stimulation in vivo we showed that co-tuned networks in A1 rapidly rebalance their activity and are now testing which cell ensembles underlie perception.
More information here.
How does cortical function change with age and how can we prevent the change?
Age-related hearing loss (presbycusis) is very common in the aged population. The most evident deficit is difficulty listening under challenging conditions, for example in noisy restaurants or bars. This difficulty in hearing is a major contributor to developing dementia. Much prior work in many labs has focused on age-related changes to the inner ear. However, we know much less about the age-related changes in the brain that affect auditory processing. Thus, we embarked on studies revealing how age changes the processing of sound information in the auditory cortex and what the underlying circuit changes are, with the goal to prevent or reverse these changes.
So far our work in mice has shown that aging increases correlated activity between neurons in the auditory cortex. This reduction in response diversity leads to deficits in sound encoding. In mice trained to detect tones in noise, we found that aging reduces the ability to suppress responses to background noise, reducing the amount of relevant stimulus information. In parallel in vitro studies we revealed the underlying circuit changes. We have also embarked on testing promising strategies to prevent age-related hearing loss and hope that such strategies can eventually be applied to humans.
More information here
How does visual deprivation affect hearing?
Sensory systems do not work in isolation. It is well known that visual deprivation (such as blindness) can lead to improved auditory abilities. However, the underlying mechanisms that contribute to these “supernormal” abilities are largely unknown. We are interested in investigating what happens to other cortical areas, in particular the auditory cortex, when visual experience is altered for short time periods.
We found that brief visual deprivation (“simulated blindness”) in mice improves auditory processing and changes thalamocortical synapses and intracortical connections in the auditory cortex. Thus, some of the changes seen in auditory performance after visual deprivation are likely due to changes in the auditory cortex. Moreover, seeing changes in thalamocortical connections to auditory cortex is quite surprising, as our visual deprivations occur after the critical period and indicate that crossmodal influences can be more powerful than unimodal influences in changing cortical circuits. We are currently investigating how the interaction with the thalamus is affected by visual deprivation.
More information here
Our work is supported by NIDCD, NEI, the BRAIN initiative, and AFOSR.
