Spatial Organization of Local Inputs to Spiny Projection Neurons in the Striatum

Abstract

GABAergic interneurons are important for balanced activity of the principal projection neurons of the striatum (spiny projection neurons, SPNs) and dysfunction of striatal GABAergic interneurons can lead to movement-related disorders. Despite this importance, very little is known about the connectivity of striatal interneurons and their functional spatial arrangement. In preliminary experiments our group optogenetically identified a group of interneuron connections that had not previously been seen in paired recordings. Here we tested the hypothesis that this finding is due to long-range connections of genetically defined interneuron classes. Using a pseudotyped Rabies Viral (RV) monosynaptic retrograde tracing strategy in sparsely identified SPNS, followed by three-dimensional reconstruction, we tested the spatial attributes of connections from different striatal interneuron classes, and lateral connections between SPNs. Our results demonstrate the feasibility of an RV-dependent approach for local distance mapping and for the first time identify distinct projection properties of different striatal neuron classes. Importantly, our experiments reveal short, local connections of Fast Spiking (FS), but long-ranging projections of Low-Threshold Spiking (LTS) interneurons, which together form the majority of striatal GABAergic interneurons. These findings can resolve the opposing results from paired and optogenetic recordings and also suggest distinct signaling modalities for these two types of interneurons.