Supplementary Materials01. separate output channels. These results demonstrate the presence of heterogeneous PVBC-PC microcircuits, potentially contributing to the sparse and distributed structure of hippocampal network activity. Introduction The mammalian hippocampus plays a critical role in learning and memory processes, by transforming input from associative neocortical regions and sending output primarily through long-distance projecting pyramidal cells in the CA1 region (PCs). These outputs target a number of brain areas, including the medial prefrontal cortex (mPFC), medial entorhinal cortex (MEC), and amygdala (AMG) (Cenquizca and Swanson, 2007), potentially coordinating the interactions amongst brain areas during mnemonic functions (Maren and Quirk, 2004; Fanselow and Poulos, 2005). Heterogeneity across the CA1 PC population is recognized along the radial axis (superficial to deep), marked by differential expression of the neurochemical markers (e.g., calbindin and zinc; Physique 1A), and in long-range projection patterns (Baimbridge and Miller, 1982; Slomianka et al., Betanin distributor 2011). Whereas the CA1 region as a whole is known Betanin distributor to be the general output of the hippocampus proper, how the heterogeneous PCs integrate into the CA1 circuit remains unknown. Open up in another window Body 1 nonuniform concentrating on of CA1 Computers by PVBCs(A) Best still left: Schematic sketching illustrates the deep and superficial subdivisions from the CA1 somatic level; Bottom: Distinctions in the mobile compactness and width from the deep and superficial sublayers along septo-temporal (dorso-ventral) PIK3CA axis from the hippocampus (discover also Section 4 in Supplementary Experimental Techniques and Slomianka et al., 2011); Best correct: Calbindin-expression in the superficial sublayer in the septal CA1. Size club: 20m. Rad.: stratum radiatum; Ori.: oriens. (B) The reconstruction of the superficial (blue) and a deep Computer (green) innervated with a common presynaptic PVBC (soma and dendrites, dark; axons, grey). L.M.: Stratum lacunosum-moleculare; Pyr., stratum pyramidale. Size club: 100m. Insets: light microscope picture of the PVBC, sPC and dPC (best left), scale club: 100m; tdTomato (TOM, best right) appearance in the documented PVBC, scale club: 10m. (C and D) Representative traces Betanin distributor from matched recordings in the septal (C) and temporal (D) CA1, displaying IPSCs (averages: heavy lines) within an sPC (blue) and dPC (green) evoked by APs in the presynaptic PVBCs. (E) Overview data from the effective unitary IPSCs (euIPSCs). (F) Connection possibility from PVBCs to Computers. Numbers in pubs reveal connected/examined pairs. (G) Overview of somatic ranges between your PVBC-sPC or PVBC-dPC pairs in the septal (still left) and temporal (best) CA1 in Statistics 1C to F. (H) Ranges through the Pyr/Rad border from the matched recorded Computers and PVBCs in the septal (still left) and temporal (right) CA1. (I) Plots of euIPSC amplitude against distance of PCs from Pyr/Rad border; red lines: linear fits to data. (J) Number of putative axon terminals of single PVBCs on single sPCs (n=10) and dPCs (n=10). (K) Relative number of somatic to proximal dendritic boutons of single PVBCs on single sPCs (n=10) and dPCs (n=10); data normalized by Betanin distributor the average number of dendritic boutons in each group. (L) Summary data of the number of putative synaptic PV+ boutons around the somata of biocytin-filled dPCs and sPCs. (M) Example traces from d/sPCs in response to blue light (10ms) in slices from PV-ChR2 expressing mice; note lack of light-evoked IPSCs in opsin-negative mice. (N) Summary data of the optogenetic experiments. Means and SEM are plotted in this and subsequent figures. Asterisks indicate p 0.05 in all figures. In particular, it is unclear what the nature of the relationship is usually between heterogeneity of PCs (Bannister and Larkman, 1995; Mizuseki et al., 2011; Deguchi et al., 2011; Graves et al., 2012) and the well-known diversity of local GABAergic hippocampal interneurons (Soltesz, 2005). Specifically, given the heterogeneous structural and functional properties of PCs in CA1, the question arises if all PCs are regulated by essentially identical local GABAergic circuits or whether hippocampal interneurons non-uniformly target specific subpopulations of CA1 PCs. The issue of heterogeneity in target selection by cortical interneurons is usually controversial. Some reports.