Functional Specialization of Presynaptic Cav2.3 Ca2+ Channels (original) (raw)
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Journal of Neuroscience, 2007
Voltage-gated Ca 2ϩ channels in presynaptic terminals initiate the Ca 2ϩ inflow necessary for transmitter release. At a variety of synapses, multiple Ca 2ϩ channel subtypes are involved in synaptic transmission and plasticity. However, it is unknown whether presynaptic Ca 2ϩ channels differ in gating properties and whether they are differentially activated by action potentials or subthreshold voltage signals. We examined Ca 2ϩ channels in hippocampal mossy fiber boutons (MFBs) by presynaptic recording, using the selective blockers -agatoxin IVa, -conotoxin GVIa, and SNX-482 to separate P/Q-, N-, and R-type components. Nonstationary fluctuation analysis combined with blocker application revealed a single MFB contained on average ϳ2000 channels, with 66% P/Q-, 26% N-, and 8% R-type channels. Whereas both P/Q-type and N-type Ca 2ϩ channels showed high activation threshold and rapid activation and deactivation, R-type Ca 2ϩ channels had a lower activation threshold and slower gating kinetics. To determine the efficacy of activation of different Ca 2ϩ channel subtypes by physiologically relevant voltage waveforms, a six-state gating model reproducing the experimental observations was developed. Action potentials activated P/Q-type Ca 2ϩ channels with high efficacy, whereas N-and R-type channels were activated less efficiently. Action potential broadening selectively recruited N-and R-type channels, leading to an equalization of the efficacy of channel activation. In contrast, subthreshold presynaptic events activated R-type channels more efficiently than P/Q-or N-type channels. In conclusion, single MFBs coexpress multiple types of Ca 2ϩ channels, which are activated differentially by subthreshold and suprathreshold presynaptic voltage signals.
Synapse, 1996
Long-term potentiation (LTP) observed at the synapses of mossy fiber-CA3 (MF-CA3) pathway differs from that observed at the Schaffer collateral-CAl pathway (SC-CAl), in being independent of N-methyl-D-aspartate (NMDA) receptors. The induction and expression mechanisms of MF-CA3 LTP remain to be determined. We have compared the occurrence and magnitude of LTP with that oftwo other indicators of presynaptic plasticity, post-tetanic potentiation (PTP) and paired-pulse facilitation in control brain slices from youngrats and in slices treated with phorbol-12,13-diacetate (PDAc), a protein kinase C activator. Paired-pulse facilitation is a potentiation of the second of two responses at intervals of tens of milliseconds and is due to a presynaptic calcium increase. Tetanic stimulation of mossy fibers induced LTP is area CA3 in only 64% of slices. In those slices that showed LTP, the size of the PTP was significantly greater than in those slices that did not, and the degree of correlation between LTP and PTP amplitude overall was r = 0.7. The degree of paired-pulse facilitation before tetanic stimulation was also positively correlated to the occurrence and magnitude of LTP and PTP after tetanic stimulation. The correlation coefficient between PTP and PPF was 0.749 for all slices studied, while that between LTP and PPF was 0.835 overall. Application of PDAc potentiated synaptic transmission and abolished paired-pulse facilitation (control ratio of second to first response, 2.1; after PDAc ratio 0.8) and LTP. PTP was absent at the control stimulus intensity in PDAc, but was apparent if the stimulus intensity was reduced to give a response of the same amplitude as before administration of PDAc. Stable LTP was also accompanied by a marked decrease in paired-pulse facilitation. These data suggest that MF-CA3 LTP, PTP and paired-pulse facilitation share common mechanisms and are all at least primarily of presynaptic origin. The occurrence of large paired-pulse facilitation or PTP is a predictor of a preparation which will show LTP. It is likely that presynaptic [Ca2+], is a n essential factor in LTP, PTP and paired-pulse facilitation, as well as the potentiation induced by application of PDAc, but the factors which determine whether or not [Caa+], rises following these various stimuli are not clear from the techniques used in these investigations. o 1996 Wiley-Liss, Inc.
Neuron, 2000
and augmentation (Griffith, 1990; Salin et al., 1996), coexist with long-lasting forms, such as posttetanic potentiation (PTP; Griffith, 1990) and NMDAR-independent long-Summary term potentiation (LTP; Johnston et al., 1992; Nicoll and Malenka, 1995). These forms of plasticity are thought to Analysis of presynaptic determinants of synaptic strength has been difficult at cortical synapses, mainly be expressed mainly presynaptically (Zalutsky and Nicoll, 1990), but the mechanisms and final molecular targets due to the lack of direct access to presynaptic elements. Here we report patch-clamp recordings from of the modifications (presynaptic ion channels, release machinery, or both) have not been identified. mossy fiber boutons (MFBs) in rat hippocampal slices. The presynaptic action potential is very short during The shape of the presynaptic action potential is of fundamental importance in determining timing and low-frequency stimulation but is prolonged up to 3-fold during high-frequency stimulation. Voltage-gated K ؉ strength of synaptic transmission (Augustine, 1990; Sabatini and Regehr, 1999). The duration of the presynaptic channels in MFBs inactivate rapidly but recover from inactivation very slowly, suggesting that cumulative spike is probably not fixed but may be subject to shortand long-term regulation. In pituitary nerve terminals of K ؉ channel inactivation mediates activity-dependent spike broadening. Prolongation of the presynaptic the rat, short-term spike broadening (on the timescale of seconds) is induced by high-frequency stimulation voltage waveform leads to an increase in the number of Ca 2؉ ions entering the terminal per action potential and is presumably mediated by K ϩ channel inactivation (Jackson et al., 1991). In presynaptic elements of inverte-and to a consecutive potentiation of evoked excitatory postsynaptic currents at MFB-CA3 pyramidal cell syn-brate neurons, long-lasting spike broadening (on the timescale of minutes or longer) is induced by neuromod-apses. Thus, inactivation of presynaptic K ؉ channels contributes to the control of efficacy of a gluta-ulators and is believed to be mediated by K ϩ channel modulation (Byrne and Kandel, 1996). Whether dynamic matergic synapse in the cortex. changes in presynaptic spike duration also occur at fasttransmitting synapses in the mammalian CNS remains,
Neuron, 2005
Is the absence of Na + channels from presynaptic terminals a general phenomenon that also extends to cor-Physiologisches Institut der Universität Freiburg Hermann-Herder-Strasse 7 tical boutons? Unlike peripheral axons, central axons often show extensive branching, and the majority of D-79104 Freiburg Germany synaptic boutons emerge from these axons in an en passant manner. Both axonal branches and en passant boutons may generate a substantial electrical load to Summary the invading AP (Goldstein and Rall, 1974; Lüscher and Shiner, 1990a, 1990b). Although the reliability of con-Action potentials in central neurons are initiated near duction of APs in cortical axons remains controversial the axon initial segment, propagate into the axon, and (Koester and Sakmann, 2000; Cox et al., 2000; Debanne finally invade the presynaptic terminals, where they et al., 1997; reviewed by Debanne, 2004), computatrigger transmitter release. Voltage-gated Na + channels
Cerebral Cortex, 2005
To study the type of presynaptic calcium channels controlling transmitter release at synaptic connections displaying depression or facilitation, dual whole cell recordings combined with biocytin labelling were performed in acute slices from motor cortex of 17-to 22-day-old rats. Layer V postsynaptic interneurons displayed either fast spiking (FS) (n 5 12) or burst firing (BF) (n 5 12) behaviour. The axons of FS cells ramified preferentially around pyramidal cell somata, while BF cell axons ramified predominately around pyramidal cell dendrites. Synapses between pyramidal cells and FS cells displayed brief train depression (n 5 12). Bath application of v-Agatoxin IVA (0.5 mM), blocking P/Q-type calcium channels, decreased mean peak amplitudes of the EPSPs to 40% of control EPSPs (n 5 8). Failure rate of the EPSPs after the first presynaptic action potential increased from 9 6 11 to 28 6 15%. This was associated with an increase in paired pulse ratio of 152 6 44%. v-Conotoxin GVIA (1-10 mM), selectively blocking N-type calcium channels, had no effect on peak amplitudes or frequency dependent properties of these connections (n 5 5). Synapses from pyramidal cells to BF cells displayed brief train facilitation (n 5 8). Application of v-Conotoxin in these connections decreased peak amplitudes of the EPSPs to 15% of control EPSPs (n 5 6) and decreased the paired pulse ratio by 41 6 30%. v-Agatoxin did not have any significant effect on the EPSPs elicited in BF cells. This study indicates that P/Q-type calcium channels are associated with transmitter release at connections displaying synaptic depression, whereas N-type channels are predominantly associated with connections displaying facilitation.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2001
The possibility that R-type calcium channels contribute to fast glutamatergic transmission in the hippocampus has been assessed using low concentrations of NiCl(2) and the peptide toxin SNX 482, a selective antagonist of the pore-forming alpha(1E) subunit of R-type calcium channel. EPSPs or EPSCs were recorded in the whole-cell configuration of the patch-clamp technique mainly from CA3 hippocampal neurons. Effects of both NiCl(2) and SNX 482 were tested on large (composite) EPSCs evoked by mossy and associative-commissural fiber stimulation. NiCl(2) effects were also tested on minimal EPSPs-EPSCs. Both substances reduced the amplitude of EPSPs-EPSCs. This effect was associated with an increase in the number of response failures of minimal EPSPs-EPSCs, an enhancement of the paired-pulse facilitation ratios of both minimal and composite EPSCs, and a reduction of the inverse squared coefficient of variation (CV(-2)). The reduction of CV(-2) was positively correlated with the decrease i...
Bidirectional Hebbian Plasticity at Hippocampal Mossy Fiber Synapses on CA3 Interneurons
Journal of Neuroscience, 2008
Hippocampal area CA3 is critically involved in the formation of non-overlapping neuronal subpopulations ("pattern separation") to store memory representations as distinct events. Efficient pattern separation relies on the strong and sparse excitatory input from the mossy fibers (MF) to pyramidal cells and feed-forward inhibitory interneurons. However, MF synapses on CA3 pyramidal cells undergo LTP, which, if unopposed, will degrade pattern separation as MF activation will now recruit additional CA3 pyramidal cells. Here we demonstrate MF LTP in stratum lacunosummoleculare (L-M) interneurons induced by the same stimulation protocol that induces MF LTP in pyramidal cells. This LTP was NMDAR-independent, and occurred at MF Ca 2+ -impermeable (CI) AMPAR synapses. LTP was prevented by with voltage clamping the postsynaptic cell soma during HFS, intracellular injections of the Ca 2+ chelator BAPTA (20 mM) or bath applications of the Ltype Ca 2+ channel blocker nimodipine (10 µM). We propose that MF LTP in L-M interneurons preserves the sparsity of pyramidal cell activation, thus allowing CA3 to maintain its role in pattern separation. In the presence of the mGluR1α antagonist LY367385 (100 µM) the same HFS that induces MF LTP in naïve slices triggered NMDAR-independent MF LTD. This LTD, like LTP, required activation of the L-type Ca 2+ channel, and also was induced following blockade of IP3 receptors with heparin (4mg/mL) or the selective depletion of receptor-gated Ca 2+ stores with ryanodine (10 or100 µM). We conclude that L-M interneurons are endowed with Ca 2+ signaling cascades suitable for controlling the polarity of MF long-term plasticity induced by joint pre-and postsynaptic activities.
The Journal of Physiology, 2007
P/Q-type and N-type calcium channels mediate transmitter release at rapidly transmitting central synapses, but the reasons for the specific expression of one or the other in each particular synapse are not known. Using whole-cell patch clamping from in vitro slices of the auditory brainstem we have examined presynaptic calcium currents (I pCa ) and glutamatergic excitatory postsynaptic currents (EPSCs) at the calyx of Held synapse from transgenic mice in which the α 1A pore-forming subunit of the P/Q-type Ca 2+ channels is ablated (KO). The power relationship between Ca 2+ influx and quantal output was studied by varying the number of Ca 2+ channels engaged in triggering release. Our results have shown that more overlapping Ca 2+ channel domains are required to trigger exocytosis when N-type replace P/Q-type calcium channels suggesting that P/Q type Ca 2+ channels are more tightly coupled to synaptic vesicles than N-type channels, a hypothesis that is verified by the decrease in EPSC amplitudes in KO synapses when the slow Ca 2+ buffer EGTA-AM was introduced into presynaptic calyces.