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. 2017 Jul 19;8:15878. doi: 10.1038/ncomms15878

Figure 9. TRPV1 affects synaptic plasticity in the Schaffer collateral pathway via promoting innervation of OLM cells.

Figure 9

(a) Scheme of putative connections of a TRPV1-expressing OLM cell in the stratum oriens. OLM cells inhibit the temporoammonic (TA) pathway from the entorhinal cortex, and disinhibit the Schaffer collateral pathway from the CA3 region, thus promoting CA3 input, and reducing EC input, to CA1 pyramidal cells. (b) Illustration of stimulating and recording electrode positions for LTP recordings performed in the Schaffer collateral pathway. (c) LTP induced by 1XTET-LTP in the Schaffer collateral pathway is reduced in TRPV1 KOs compared WT (n=10 sections each from WT and TRPV1 KO mice; error=s.e.m.). (d) Immunostain of hippocampal sections from a β2-EGFP nAChR mouse with TRPV1 and SOM, and with TRPV1 and reelin (e); TRPV1 and β2-EGFP nAChRs are expressed in the same population of OLM neurons. (f) Quantitation of β2-EGFP nAChR with TRPV1, SOM, and reelin-expressing cells in the stratum oriens (n=8, 4 and 3 images for TRPV1, SOM, and reelin, respectively, from four hippocampal sections). (g) Calcium imaging of Fluo-4 signal in dissociated hippocampal neurons stimulated sequentially with 5 μM nicotine and 1 μM capsaicin. 80% of cells that responded to capsaicin also responded to nicotine; of 112 cells that responded to field stimulation, 17 responded to nicotine and capsaicin, four to capsaicin alone, and 22 to nicotine alone. (h) Representative traces of hippocampal neurons responding to both nicotine and capsaicin. (i) LTP in the Schaffer collateral pathway of TRPV1 KOs is restored to WT levels by 5 μM nicotine exposure 20 min before and during recording (n=10 slices each for WT, TRPV1 KO, WT + nicotine, and TRPV1 KO + nicotine; significance determined by Student's t-test, error=s.e.m.). (j) The rescue of LTP in TRPV1 KOs by nicotine is not mediated by α4β2 or α7-containing nicotinic receptors—blocked by 100 nM DHBE and 100 nM MLA, respectively—but is mediated by α2 receptors blocked by addition of 1 μM MEC, which blocks all nicotinic receptors including α2 (n=7 slices each for TRPV1 KO + nicotine/DHBE/MLA and for TRPV1 KO + nicotine/DHBE/MLA/MEC; error=s.e.m.).