Research Unit 5159

Short Summary: Dysregulation of inhibition is one of the hallmarks of neuropsychiatric disorders, often resulting in sensory and cognitive deficits. A central question is how sensory experience during development influences the connectivity and function of inhibitory neurons during cortical sensory processing. We are particularly interested in how inhibitory interneurons in the auditory and visual cortices integrate bottom-up sensory inputs together with top-down feedback and influence ongoing sensory processing. Higher order projections to sensory cortical areas converge on layer 1 (L1), the primary site for integration of top-down information via the apical dendrites of pyramidal neurons and L1 cortical interneurons (cINs). We examined the integration of bottom-up sensory inputs from the thalamus and higher-order projections from the anterior cingulate cortex onto the L1 cINs in the primary visual cortex (V1). We discovered that during development, thalamic inputs predominantly target NDNF+ L1 cINs cells and are crucial for the later enhancement of top-down connectivity. Interestingly, these projections were found to be critical for the subsequent strengthening of top-down inputs from the anterior cingulate cortex. Sensory deprivation or selective removal of thalamic afferents blocked this phenomenon, while early activation of the anterior cingulate cortex resulted in a premature strengthening of these top-down afferents, which was dependent on thalamic inputs. Additionally, our longitudinal 2-photon calcium imaging from neonatal stages to adulthood in the mouse V1 revealed the dynamic activity of these cells in response to both external sensory stimuli and internal state dependent signals. Similarly, we investigated the responses of L1 and L2/3 neurons in the auditory cortex. Our results outline a framework for the experience-dependent maturation of top-down processing in sensory cortices and its disruption in neuropsychiatric disorders.