Gyorgy Lur | bioRxiv Science

bioRxiv2016

Developmental dysfunction of VIP interneurons impairs cortical circuits

Current evidence suggests that dysregulation of GABAergic interneurons contributes to neural and behavioral deficits in several neurodevelopmental disorders, including schizophrenia. However, there are multiple populations of interneurons and their respective roles in psychiatric disease remain poorly explored. Neuregulin 1 (NRG1) and its interneuron-specific tyrosine kinase receptor ERBB4 are risk genes for schizophrenia, and the Nrg1/ErbB4 pathway is important for normal cortical development. Using a conditional ErbB4 deletion model, we directly tested the role of vasoactive intestinal peptide (VIP)-expressing interneurons in schizophrenia-related deficits in vivo. ErbB4 removal from VIP interneurons during development leads to changes in their activity, along with severe dysregulation of the temporal organization and state-dependence of cortical activity. As a result of these neural circuit alterations, animals in which VIP interneurons lack ErbB4 exhibit behavioral abnormalities, reduced cortical responses to sensory stimuli, and impaired sensory learning. Our data support a key role for VIP interneurons in normal cortical circuit development and suggest that their disruption contributes to pathophysiology in the ErbB4 model of schizophrenia. These findings provide a new perspective on the role of GABAergic interneuron diversity in the disruption of cortical function in complex psychiatric diseases.

Neuroscience↗

bioRxiv2015

Projection-specific visual feature encoding by layer 5 cortical subnetworks.

Primary neocortical sensory areas act as central hubs, distributing afferent information to numerous cortical and subcortical structures. However, it remains unclear whether each downstream target receives distinct versions of sensory information. We used in vivo calcium imaging combined with retrograde tracing to monitor visual response properties of three distinct subpopulations of projection neurons in primary visual cortex. While there is overlap across the groups, on average corticotectal (CT) cells exhibit lower contrast thresholds and broader tuning for orientation and spatial frequency in comparison to corticostriatal (CS) cells, while corticocortical (CC) cells have intermediate properties. Noise correlational analyses support the hypothesis that CT cells integrate information across diverse layer 5 populations, whereas CS and CC cells form more selectively interconnected groups. Overall, our findings demonstrate the existence of functional subnetworks within layer 5 that may differentially route visual information to behaviorally relevant downstream targets.

Neuroscience↗