An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes.

In recent years, we and others have identified a number of enhancers that, when incorporated into rAAV vectors, can restrict the transgene expression to particular neuronal populations. Yet, viral tools to access and manipulate fine neuronal subtypes are still limited. Here, we performed systematic analysis of single cell genomic data to identify enhancer candidates for each of the cortical interneuron subtypes. We established a set of enhancer-AAV tools that are highly specific for distinct cortical interneuron populations and striatal cholinergic neurons. These enhancers, when used in the context of different effectors, can target (fluorescent proteins), observe activity (GCaMP) and manipulate (opto- or chemo-genetics) specific neuronal subtypes. We also validated our enhancer-AAV tools across species. Thus, we provide the field with a powerful set of tools to study neural circuits and functions and to develop precise and targeted therapy.

Primary auditory thalamus relays directly to cortical layer 1 interneurons.

Inhibitory interneurons within cortical layer 1 (L1-INs) integrate inputs from diverse brain regions to modulate sensory processing and plasticity, but the sensory inputs that recruit these interneurons have not been identified. Here we used monosynaptic retrograde tracing and whole-cell electrophysiology to characterize the thalamic inputs onto two major subpopulations of L1-INs in the mouse auditory cortex. We find that the vast majority of auditory thalamic inputs to these L1-INs unexpectedly arise from the ventral subdivision of the medial geniculate body (MGBv), the tonotopically-organized primary auditory thalamus. Moreover, these interneurons receive robust functional monosynaptic MGBv inputs that are comparable to those recorded in the L4 excitatory pyramidal neurons. Our findings identify a direct pathway from the primary auditory thalamus to the L1-INs, suggesting that these interneurons are uniquely positioned to integrate thalamic inputs conveying precise sensory information with top-down inputs carrying information about brain states and learned associations.