JournalNeural Excitability, Synapses, and Glia

Brain-Wide Maps of Synaptic Input to Cortical Interneurons

Characteristics of infected interneurons in SST, VIP, and PV-Cre mice. A, SST-expressing interneurons are known to heavily innervate the distal dendrites of cortical pyramidal cells. This is evidenced by the high density of projections in superficial layers, including high axon density in layer 1. The distal dendrites of some retrogradely infected pyramidal cells are also visible extending into layer 1. RV, magenta; DAPI, cyan. This is consistent for all panels. Scale bar, 50 μm. B, Rabies-infected VIP-expressing interneurons are largely bipolar in nature, with a primary neurite extending into layer 1, and the other projecting to deeper layers of cortex. The cell bodies of these neurons are primarily found in superficial cortical layers. Scale bar, 50 μm. C, As expected from the properties of PV+ interneurons, very few projections are detected in layer 1 of PV-Cre mice following AAV and RV infection. However, there is heavy innervation of deeper cortical layers. Scale bar, 50 μm. D, Fluorescently labeled basket-type synapses are prevalent in PV-Cre mice, ringing neuronal somata in deeper layers of cortex. This is consistent with efficient targeting to PV-expressing basket cells in this mouse line. Scale bar, 25 μm.

Cortical inhibition is mediated by diverse inhibitory neuron types that can each play distinct roles in information processing by virtue of differences in their input sources, intrinsic properties, and innervation targets. Previous studies in brain slices have demonstrated considerable cell-type specificity in laminar sources of local inputs. In contrast, little is known about possible differences in distant inputs to different cortical interneuron types. We used the monosynaptic rabies virus system, in conjunction with mice expressing Cre recombinase in either parvalbumin-positive, somatostatin-positive (SST+), or vasoactive intestinal peptide-positive (VIP+) neurons, to map the brain-wide input to the three major nonoverlapping classes of interneurons in mouse somatosensory cortex. We discovered that all three classes of interneurons received considerable input from known cortical and thalamic input sources, as well as from probable cholinergic cells in the basal nucleus of Meynert. Despite their common input sources, these classes differed in the proportion of long-distance cortical inputs originating from deep versus superficial layers. Similar to their laminar differences in local input, VIP+ neurons received inputs predominantly from deep layers while SST+ neurons received mostly superficial inputs. These classes also differed in the amount of input they received. Cortical and thalamic inputs were greatest onto VIP+ interneurons and smallest onto SST+ neurons.

Wall, N.R., De La Parra, M., Sorokin, J.M., Taniguchi, H., Huang, Z.J., and Callaway, E.M. (2016). Brain-Wide Maps of Synaptic Input to Cortical Interneurons. J. Neurosci. 36, 4000–4009.