Auditory System . Neuronal Circuit . Functional Network . Cortical Development Critical Period . Interneuron Diversity

Brain and Sound Lab

Development and function of neuronal circuitsin the central auditory system

Sounds and hearing play a pivotal role in human communication. People who suffer from central auditory processing abnormalities are affected in their daily lives and might not be able to appreciate even the most basic verbal communication. Tinnitus, in which phantom sounds are experienced in the absence of acoustic stimulation, is an example of pathology of the central auditory system. Ten percent of the human population suffers from auditory cortex disorders, yet we understand very little about its role in making sense of sounds.

In our lab we study the development and function of the auditory cortex. We combine optogenetics, in vivo physiology, voltage-sensitive dye imaging and behavioral assays to explore the role of its neuronal circuits. The goal of our research is to give a new insight into the function of the auditory system and to lead to new ways of reinstating normal connectivity in cases of abnormal signal processing.
Ongoing work is directed towards three main questions: 1) How do auditory cortical responses develop and how can they be modified? 2) What neuronal circuits are involved in specific sound features, and how do they influence behavior? 3)What influences does the environment have on regulating these auditory neuronal circuits?

Neuronal responses to different sound features develop asynchronously
Using in vivo electrophysiological recording and voltage-sensitive dye imaging in the mouse auditory cortex, we are characterizing the development of auditory responses to sounds of increasing complexity, like pure frequency tones, frequency or amplitude-modulated sweeps. We also determine the time windows – known as critical periods for plasticity – during which brain organisation can be modified by passive sound exposure.
Our results indicate that responses to sound features of increasing complexity mature asynchronously. Passive exposure to these sound features changes neuronal circuit organisation during distinct time windows (Fig. 1). Interestingly, these critical periods coincide with the maturation of sound feature representation. This indicates that sensory development and plasticity involve the same cortical substrate.We are currently studying the underlying cortical circuits to shed a new light on how the brain processes different sounds during development.

Interneurons enhance tone frequency selectivity in auditory cortex
Using optogenetics combined with electrophysiology, we are studying the role of neuronal subpopulations in shaping responses to specific sound features. We are also assessing the behavioural consequences of controlling these neuronal subgroups in auditory relevant tasks. The subpopulations we now focus on are inhibitory neuron subclasses, like the parvalbumin-, somatostatin- or vasointestinal protein-expressing neurons.
Our results indicate that inhibitory neurons enhance tone frequency selectivity in response to pure frequency tones (Fig. 2). These changes are correlated with changes at the behavioural level: increasing frequency selectivity at the neuronal level with optogenetics also increases the ability to discriminate to sounds in a go/no go behavioural task. We are currently determining whether different types of interneurons play a different role in this frequency selectivity, and also whether these subclasses of neurons have a different role in responding to more complex sounds.

Noise exposure modifies brain organisation differently in a developing than in a fully mature brain
By exposing mice to continuous white noise during several days, we are probing the influence of the environment on the rules regulating the organisation and plasticity of auditory circuits.
Our results indicate that the external environment can have very different consequences on a developing or a mature brain. We are currently determining the specific cell types and circuits modified by these environmental exposures, and to what extend these changes can be reversed. This research will have an impact on the way we look at the constant occupational noise that we and our children are exposed to on a daily basis, ranging from background music, construction work or even psychosocial stress.

Fig. 1: Critical periods for plasticity are numerous and asynchronous. The time window of enhanced plasticity to passive pure frequency tones exposure arises earlier than the one for frequency modulated sweep exposure.

Fig. 2: Inhibitory neurons enhance tone frequency selectivity in auditory cortex A. Schematic of electrophysiological recording in mouse auditory cortex. The red line illustrates an electrode shaft with 4 recording sites in different layers of the cortex. Inset: representative peristimulus time histogram following a 50ms pure frequency tone exposure. B. C. Example neural responses to pure frequency tones indicate that neurons respond stronger to some frequencies than to others. These frequency selectivities are enhanced (B) or decreased (C) when optogenetic manipulations activate or silence parvalbumin-expressing (PV) neurons, respectively.