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Letzkus Lab

Top-down afferents to neocortical layer 1
 
Top-down afferents to neocortical layer 1

Information about past experiences and current aims is a central element of all higher brain functions, but our understanding of such of internally-generated top-down signals in health and disease is limited. We use a combination of imaging, electrophysiology, cell-type specific targeting, optogenetics, viral tracing and behavior to dissect these mechanisms in the auditory cortex.

Neocortex is the largest and most powerful area of the mammalian brain. This region has expanded and differentiated the most during evolution, mediates many of the capacities that distinguish humans from their closest relatives, and also plays a central role in many psychiatric disorders. All higher cognitive functions of the neocortex are enabled by bringing together two distinct streams of information: a ‘bottom-up’ stream carrying signals from the surrounding environment, and a ‘top-down’ stream that transmits internally-generated information encoding our previous experiences and current aims.
Whereas decades of work have addressed processing of sensory bottom-up information, our understanding of internally-generated information is still in its infancy. Our work aims to fill this gap by elucidating the mechanisms and consequences of top-down information processing in the auditory cortex. Using a combination of cutting-edge approaches (including 2-photon & 1-photon imaging, electrophysiology, optogenetics, viral tracing and computational analyses) together with behavioral paradigms, we address the following questions:

 

1) Which brain-wide afferents convey which type of top-down information to neocortex?

2) How are these top-down signals translated by local inhibitory interneurons to flexibly adjust circuit function?

3) Which aspects of information processing is subject to top-down modulation?

4) How does top-down information optimize brain function for complex, naturalistic behaviors?

5) How do perturbations of top-down processes contribute to brain disorders?
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