Triple Function of Synaptotagmin 7 Ensures Efficiency of High-Frequency Transmission at Central GABAergic Synapses
2017; 21 (8): 2082–89
Synaptotagmins: That's Why So Many
2017; 94 (4): 694–96
Synaptotagmin 7 (Syt7) is thought to be a Ca2+ sensor that mediates asynchronous transmitter release and facilitation at synapses. However, Syt7 is strongly expressed in fast-spiking, parvalbumin-expressing GABAergic interneurons, and the output synapses of these neurons produce only minimal asynchronous release and show depression rather than facilitation. To resolve this apparent contradiction, we examined the effects of genetic elimination of Syt7 on synaptic transmission at the GABAergic basket cell (BC)-Purkinje cell (PC) synapse in cerebellum. Our results indicate that at the BC-PC synapse, Syt7 contributes to asynchronous release, pool replenishment, and facilitation. In combination, these three effects ensure efficient transmitter release during high-frequency activity and guarantee frequency independence of inhibition. Our results identify a distinct function of Syt7: ensuring the efficiency of high-frequency inhibitory synaptic transmission.
View details for DOI 10.1016/j.celrep.2017.10.122
View details for Web of Science ID 000416216700007
View details for PubMedID 29166601
View details for PubMedCentralID PMC5863544
Synaptotagmin 2 Is the Fast Ca2+ Sensor at a Central Inhibitory Synapse
2017; 18 (3): 723–36
Synaptotagmin 7 (Syt7) was originally identified as a slow Ca2+ sensor for lysosome fusion, but its function at fast synapses is controversial. The paper by Luo and Südhof (2017) in this issue of Neuron shows that at the calyx of Held in the auditory brainstem Syt7 triggers asynchronous release during stimulus trains, resulting in reliable and temporally precise high-frequency transmission. Thus, a slow Ca2+ sensor contributes to the fast signaling properties of the calyx synapse.
View details for DOI 10.1016/j.neuron.2017.05.011
View details for Web of Science ID 000401415100002
View details for PubMedID 28521120
Alleviation of neuropathic pain by regulating T-type calcium channels in rat anterior cingulate cortex
2015; 11: 7
GABAergic synapses in brain circuits generate inhibitory output signals with submillisecond latency and temporal precision. Whether the molecular identity of the release sensor contributes to these signaling properties remains unclear. Here, we examined the Ca2+ sensor of exocytosis at GABAergic basket cell (BC) to Purkinje cell (PC) synapses in cerebellum. Immunolabeling suggested that BC terminals selectively expressed synaptotagmin 2 (Syt2), whereas synaptotagmin 1 (Syt1) was enriched in excitatory terminals. Genetic elimination of Syt2 reduced action potential-evoked release to ∼10%, identifying Syt2 as the major Ca2+ sensor at BC-PC synapses. Differential adenovirus-mediated rescue revealed that Syt2 triggered release with shorter latency and higher temporal precision and mediated faster vesicle pool replenishment than Syt1. Furthermore, deletion of Syt2 severely reduced and delayed disynaptic inhibition following parallel fiber stimulation. Thus, the selective use of Syt2 as release sensor at BC-PC synapses ensures fast and efficient feedforward inhibition in cerebellar microcircuits.
View details for DOI 10.1016/j.celrep.2016.12.067
View details for Web of Science ID 000396470600013
View details for PubMedID 28099850
View details for PubMedCentralID PMC5276807
Low-Dose Sevoflurane Promotes Hippocampal Neurogenesis and Facilitates the Development of Dentate Gyrus-Dependent Learning in Neonatal Rats
2015; 7 (2)
It has been demonstrated that administration of T-type calcium channel (TCC) inhibitors could relieve the neuropathic pain by intraperitoneally or intrathecally. TCCs are not only expressed in dorsal root ganglia or dorsal horn, but also in some of the pain associated brain regions. In the present study, we sought to investigate whether modulating TCCs in the anterior cingulate cortex (ACC) could alleviate the neuropathic pain.(1) Cav3.2 was up regulated in rat ACC after chronic constriction injury (CCI). (2) T-type calcium current intensity was increased in CCI animal model. (3) TCC inhibitor reduced miniature excitatory postsynaptic currents frequency of ACC neurons in CCI animal model. (4) TCC inhibitor suppressed the firing rate of ACC neurons in CCI animal model. (5) Both mechanical and thermal allodynia were partially relieved by ACC microinjection with TCC inhibitor.TCCs in the ACC may be contributing to the maintenance of neuropathic pain, and the neuropathic pain can be alleviated by inhibiting the neuronal activity of ACC through modulating the TCCs.
View details for DOI 10.1186/s12990-015-0008-3
View details for Web of Science ID 000351125000001
View details for PubMedID 25885031
View details for PubMedCentralID PMC4357203
Huge body of evidences demonstrated that volatile anesthetics affect the hippocampal neurogenesis and neurocognitive functions, and most of them showed impairment at anesthetic dose. Here, we investigated the effect of low dose (1.8%) sevoflurane on hippocampal neurogenesis and dentate gyrus-dependent learning. Neonatal rats at postnatal day 4 to 6 (P4-6) were treated with 1.8% sevoflurane for 6 hours. Neurogenesis was quantified by bromodeoxyuridine labeling and electrophysiology recording. Four and seven weeks after treatment, the Morris water maze and contextual-fear discrimination learning tests were performed to determine the influence on spatial learning and pattern separation. A 6-hour treatment with 1.8% sevoflurane promoted hippocampal neurogenesis and increased the survival of newborn cells and the proportion of immature granular cells in the dentate gyrus of neonatal rats. Sevoflurane-treated rats performed better during the training days of the Morris water maze test and in contextual-fear discrimination learning test. These results suggest that a subanesthetic dose of sevoflurane promotes hippocampal neurogenesis in neonatal rats and facilitates their performance in dentate gyrus-dependent learning tasks.
View details for DOI 10.1177/1759091415575845
View details for Web of Science ID 000353223200002
View details for PubMedID 25873307
View details for PubMedCentralID PMC4720175