Attentional control of the auditory cortex – ALERT

Auditory attention is a rich and complex process that allows the mind to target specific information and filter out noise and distractions. The study of attention is central in all the cognitive neurosciences, and its dysfunction is found in many degenerative and developmental brain diseases. Despite its neurobiological importance and its strong impact on a patient’s life, brain regions controlling attention and their mode of operation remain largely unknown.

Recently, we have demonstrated in ferrets and mice that attention can modulate the activity even in the primary auditory cortex (A1), and that the encoding of acoustic features depends critically on whether the listener is engaged in active auditory tasks. Thus, receptive field properties of A1 neurons are rapidly reshaped within a few seconds to facilitate perception of behaviorally meaningful features. The primary aim of our project (ALERT) is to to explore the mechanisms of this auditory selective attention, how this reshaping occurs in A1 circuits, and what are the relative contributions of different brain structures in exerting this top-down control.

Two main relevant pathways have recently been identified in mice. The first originates from the orbitofrontal cortex (OFC), which shares direct glutamatergic connections with A1. The second is the nucleus basalis (NB), which sends cholinergic projections to A1. So far, only indirect involvement of these pathways in A1 attentional control has been shown. The project ALERT has two specific objectives: to dissect concretely the involvement of OFC-A1 and NB-A1 pathways in the control of A1 during attentive episodes, and to determine how these top-down controls could be computationally implemented.

We shall record with two-photon calcium imaging the activity of large A1 neuronal population while mice perform behavioral tasks that require discrimination between pure tones and broadband noise. We then compare the exact same neural population when the animals are listening to the same sounds but are not engaged in the task. The difference of individual cell receptive fields between active and passive contexts will serve as a landmark for attentional modulation. The involvement of OFC and NB in this modulation will be tested with an optogenetic approach silencing alternatively OFC and NB projections to A1 and determining what fraction of attentional modulation remains. Finally, we shall test four distinct mechanisms taking place either at the interface or internally in A1, and possibly relying on plasticity of neural connections. To do so, we shall computationally determine the functional couplings between A1/OFC-NB, as well as between individual cells in A1 using advanced statistical modeling and inference methods. More precisely, we will assess whether the functional connectivity between pairs of A1 cells is dynamically changed between the behavioral contexts, indicating that attentional modulation relies on synaptic plasticity within A1, or whether the functional couplings between A1 and OFC or A1 and NB are modified, pointing towards a mechanism implemented at the interface.

A deeper understanding of these fundamental mechanisms would provide a valuable foundation for further translational studies and therapeutic strategies for treating attentional disorders.