2022
DOI: 10.1073/pnas.2119636119
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Excitatory selective LTP of supramammillary glutamatergic/GABAergic cotransmission potentiates dentate granule cell firing

Abstract: Significance It is now established that many neurons can release multiple transmitters. Recent studies revealed that fast-acting neurotransmitters, glutamate and GABA, are coreleased from the same presynaptic terminals in some adult brain regions. The dentate gyrus (DG) granule cells (GCs) are innervated by the hypothalamic supramammillary nucleus (SuM) afferents that corelease glutamate and GABA. However, how these functionally opposing neurotransmitters contribute to DG information processing remai… Show more

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Cited by 14 publications
(7 citation statements)
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References 83 publications
(144 reference statements)
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“…To examine whether the co-release of glutamate and GABA exhibits the same or different release properties, we first monitored the paired-pulse ratio (PPR), an index of the change in presynaptic transmitter release (Zucker and Regehr, 2002), of glutamate/GABA co-transmission by paired stimulation (inter-stimulus interval: 100 ms). As reported previously (Hashimotodani et al, 2018; Tabuchi et al, 2022), both EPSCs and IPSCs at SuM-GC synapses exhibited paired-pulse depression (Figure 1F). Importantly, we found that PPR was significantly different between EPSCs and IPSCs; EPSCs were more depressed than IPSCs (Figure 1G) (EPSC: 0.46 ± 0.03, n = 8; IPSC: 0.6 ± 0.03, n = 8, p < 0.01, unpaired t test).…”
Section: Resultssupporting
confidence: 89%
See 1 more Smart Citation
“…To examine whether the co-release of glutamate and GABA exhibits the same or different release properties, we first monitored the paired-pulse ratio (PPR), an index of the change in presynaptic transmitter release (Zucker and Regehr, 2002), of glutamate/GABA co-transmission by paired stimulation (inter-stimulus interval: 100 ms). As reported previously (Hashimotodani et al, 2018; Tabuchi et al, 2022), both EPSCs and IPSCs at SuM-GC synapses exhibited paired-pulse depression (Figure 1F). Importantly, we found that PPR was significantly different between EPSCs and IPSCs; EPSCs were more depressed than IPSCs (Figure 1G) (EPSC: 0.46 ± 0.03, n = 8; IPSC: 0.6 ± 0.03, n = 8, p < 0.01, unpaired t test).…”
Section: Resultssupporting
confidence: 89%
“…To optogenetically stimulate SuM inputs in the DG, channelrhodopsin-2 (ChR2) was expressed in SuM neurons by injecting a Cre-dependent adeno-associated virus (AAV) encoding ChR2-eYFP (AAV-DIO-ChR2(H134R)-eYFP) into the lateral SuM of vesicular glutamate transporter 2 (VGluT2)-Cre mice (Hashimotodani et al, 2018; Hirai et al, 2022; Tabuchi et al, 2022) (Figures 1 A and 1B). Consistent with previous reports (Boulland et al, 2009; Soussi et al, 2010; Root et al, 2018; Billwiller et al, 2020; Ajibola et al, 2021), the vast majority of ChR2-eYFP-expressing SuM boutons in the DG co-expressed VGluT2 and vesicular GABA transporter (vesicular inhibitory amino acid transporter, VIAAT) (Figures 1C-1E).…”
Section: Resultsmentioning
confidence: 99%
“…Although DG GCs receive excitatory inputs from entorhinal cortex (EC-GC), the hilar mossy cell (MC-GC) 25 as well as the supramammillary nucleus, 26 , 27 we mainly focused on whether P2X7Rs regulated excitatory neurotransmission in an input specific way in EC-GC and MC-GC pathway. To this end, we specifically stimulated the two pathways by placing a stimulating electrode into the lateral and medial molecular layer of the dentate gyrus (DG), which contain EC-GC pathway fibers (lateral perforant path [LPP] and medial perforant path [MPP]) 28 ( Figure 3 A), or the inner molecular layer of the DG, which contains MC-GC pathway axons ( Figure 3 F).…”
Section: Resultsmentioning
confidence: 99%
“…This synapse-specific potentiation was associated with a significant decrease in both PPR and CV ( Figure 3B ), suggesting a presynaptic mechanism of expression, and supporting a presynaptic location of A 2A Rs. In addition, we tested whether supramammillary (SuM) inputs express functional A 2A Rs using optogenetic activation of SuM inputs (Tabuchi et al, 2022) (see Methods). Unlike MC EPSCs, SuM EPSCs were not enhanced by CGS21680 bath application ( Figure 3C ).…”
Section: Resultsmentioning
confidence: 99%