Periments to investigate the synaptic mechanisms involved inside the responses to OXT prior to and just after EGLU pretreatment. Whole cell recordings were made from 82 gastric-projecting DMV neurones from 36 rats. Perfusion of brainstem slices with OXT (100 nM) decreased the amplitude of eEPSCs in eight of 16 neurones (50 ) from 195 25 to 139 24 pA, i.e. 68 five of control (P 0.05; Fig. 4A and B). With the remaining 8 neurons, OXT enhanced the amplitude of eEPSCs in 2 neurones (13 ; 153 14 of manage amplitude) and had no effect in six neurones (38 ; 97 two of manage amplitude). A variation in the ratio with the amplitude of two evoked postsynaptic currents evoked a couple of milliseconds apart is indicative of irrespective of whether a drug is acting at a presynaptic or postsynaptic website (Travagli Williams, 1996). In neurones in which OXT decreased eEPSC amplitude, the paired pulse ratio, i.e. the ratio of the second evoked existing amplitude relative to that in the initially evoked existing, increased from 0.74 0.10 to 1.18 0.26 (N = 8; P 0.05). A presynaptic vs. postsynaptic internet site of action to reduce excitatory synaptic transmission was investigated furtherin 13 neurones in which the effect of OXT to modulate the frequency and amplitude of miniature EPSCs (mEPSCs) was examined. In six of 13 neurones (46 ), perfusion with OXT decreased the mEPSCs inter-event interval to 53 4 of manage (from 1.Vardenafil 72 0.51 to 0.92 0.28 events s-1 ; P 0.05) devoid of affecting mEPSC amplitude (35 two pA in control vs. 36 3 pA in OXT; P 0.05; Fig. 4C and D). OXT improved the inter-event interval in two neurones (174 eight of control) with out affecting mEPSC amplitude (98 four of control) and had no impact on either frequency (108 6 ) or amplitude (one hundred 1 ) in the remaining 5 neurones (P 0.05, in every single instance). These benefits recommend that, with regard to excitatory glutamatergic transmission, OXT acts presynaptically to inhibit glutamatergic synaptic transmission to a subpopulation of gastric-projecting DMV neurones.Oxytocin does not modulate inhibitory synaptic transmission to gastric-projecting DMV neuronesIn contrast to its effects on excitatory synaptic transmission, OXT did not alter the amplitude of eIPSCs in any in the 32 neurones tested (184 12 pA in control vs. 188 12 pA in OXT, i.e. 102 two of control;Figure 2. Gastroinhibition induced by OXT is mediated by activation of a non-adrenergic non-cholinergic (NANC) pathway A, representative original records from a single, fasted, animal just after microinjection of PBS (top rated) and, following a 30 min recovery, OXT (150 pmol; second trace from prime). The gastroinhibitory effect of OXT remained in the presence of constantly infused bethanechol (50 g kg-1 bolus followed by 20 g kg-1 h-1 I.V.; third trace from top).Biotin-d2-1 Continuous infusion of bethanechol and simultaneous blockade of NANC neurotransmission by bolus injection of L-NAME (ten mg kg-1 I.PMID:24670464 V.) abolished the effect of OXT (150 pmol; bottom trace). B, graphic summary of gastroinhibition created by DVC microinjections of PBS, OXT (150 pmol), OXT within the presence of systemic bethanechol, and OXT in the presence of systemic bethanechol + L-NAME. Also, the gastroinhibitory impact of OXT (pre-L-NAME) was antagonized totally within the presence of systemic L-NAME (I.V. L-NAME). P 0.05 vs. PBS; P 0.05 vs. 150 pmol OXT (pre-L-NAME).C2013 The Authors. The Journal of PhysiologyC2013 The Physiological SocietyJ Physiol 591.Oxytocin and EGLU effects in dorsal vagal complexP 0.05; Fig. 5A and B). Moreover, O.