Connectivity rules in networks of PV-expressing interneurons in the dentate gyrus of the hippocampus

The dentate gyrus is the input region of the hippocampus and plays a key role in several higher brain functions, such as grid-to-place code conversion and pattern separation (Leutgeb et al. , 2007). For these computations, the granule cell (GC)-GABAergic interneuron microcircuit plays a critical role. However, the connectivity of this important brain region is largely unknown. To determine the functional connectivity rules in the dentate gyrus, recording from multiple cells is needed (Couey et al. , 2013; Guzman et al. , 2016; Jiang et al. , 2015), including recording from several granule cells (GCs) and identified interneurons. We made simultaneous whole-cell patch-clamp recordings from GCs and parvalbumin-expressing (PV + ) interneurons in acute hippocampal slices. PV + interneurons were identified by the fluorescent expression of the td-Tomato reporter (Ai 14) in a PV-Cre mouse line. We found that excitatory connections between GC–PV + have a lower average connection probability (connection probability 9%) while spatially they are more locally confined than the inhibitory connections between PV + –GC (connection probability 26%), in a sample of 1038 pairs tested. We frequently found convergence motifs, with up to 4 GCs converging onto a single PV + interneuron. This suggests that PV + interneurons sample the activity of a distributed population of GCs by convergence, and direct their inhibitory output to a large number of GCs by divergence. In addition, we found an enrichment of mutual inhibition motifs between PV + interneurons (bidirectional chemical and mixed reciprocal chemical associated with electrical coupling). Moreover, the synaptic strength of synapses belonging to overrepresented inhibitory motifs is higher than the synapses that do not belong to motifs. Our results suggest a modular organization of the interneuron network which may be important to maximize the efficiency of separation of similar patterns of GC activation. 1. Couey JJ, Witoelar A, Zhang SJ, Zheng K, Ye J, Dunn B, Czajkowski R, Moser MB, Moser EI, Roudi Y, Witter MP (2013) Recurrent inhibitory circuitry as a mechanism for grid formation. Nat Neurosci 16:318–24. 2. Guzman SJ, Schlögl A, Frotscher M, Jonas P (2016) Synaptic mechanisms of pattern completion in the hippocampal CA3 network. Science 353:1117–1123. 3. Jiang X, Shen S, Cadwell CR, Berens P, Sinz F, Ecker AS, Patel S, Tolias AS (2015). Principles of connectivity among morphologically defined cell types in adult neocortex. Science 350:6264. 4. Leutgeb JK, Leutgeb S, Moser MB, Moser EI (2007) Pattern separation in the dentate gyrus and CA3 of the hippocampus. Science 315:961–966.