Switching Off and On of Synaptic Sites atAplysiaSensorimotor Synapses

Abstract

Using the highly plastic synapses between mechanoreceptor sensory neurons and siphon motor neurons of Aplysia as a model, we have investigated whether switching off and on of individual synaptic release sites is a strategy that is used by neurons in forms of short-term synaptic modulation with a time course of minutes to hours. We have modified some of the techniques of classical quantal analysis and examined the kinetics of synaptic depression under different stimulation protocols to answer this question. Our analysis shows that both synaptic depression caused by homosynaptic activity and synaptic facilitation induced by an endogenous facilitatory transmitter occur by means of the shutting off and turning on, respectively, of synaptic sites, without intermediate changes in the probability of release. Our findings imply that other forms of plasticity at these synapses, such as post-tetanic potentiation, long-term facilitation, and long-term potentiation, are also expressed by all-or-none changes in activity at individual sites. We thus show that in addition to the mechanisms of synaptic integration that are known to operate in single cells and networks, neurons can exercise a further layer of fine control, at the level of individual release sites.Key words: synaptic transmission; synaptic plasticity; synaptic depression; synaptic facilitation; transmitter release; quantal analysis; miniature synaptic potentials Synaptic phenomena such as long-term potentiation and depression represent cellular mechanisms that may contribute to learning (McKernan and Shinnick-Gallagher, 1997;Murphy and Glanzman, 1997;Rogan et al., 1997), as do short-term processes such as homosynaptic depression and heterosynaptic facilitation (Zucker, 1972;Byrne et al., 1993;Cohen et al., 1997). Although detailed mechanistic explanations for these phenomena are lacking, evidence has been marshalled for such general possibilities as changes in the probability of neurotransmitter release (Bolshakov and Siegelbaum, 1994;Stevens and Wang, 1994) or the insertion or activation of postsynaptic receptors (Isaac et al., 1995;Liao et al., 1995). Other studies have reported that some synapses release no neurotransmitter initially but can be recruited by various treatments (Wojtowicz et al., 1991;Charpier et al., 1995;Wang et al., 1996). We have taken advantage of the favorable properties of sensorimotor synapses of Apl ysia to examine whether shifting of synapses into and out of the active pool occurs in short-term synaptic plasticity.Modulation of sensorimotor transmission in Apl ysia contributes to changes in its responsiveness to tactile stimulation (Carew et al., 1983;Byrne et al., 1993;Stopfer and C arew, 1996;Cohen et al., 1997). Homosynaptic depression is a progressive decline in transmitter release that occurs even at low stimulation frequency (C astellucci and Kandel, 1974). Heterosynaptic facilitation is the increase in transmitter release, mediated by facilitatory transmitters such as serotonin (5HT), that follows a noxious stimulus (Brunelli e...

Activity-dependent calpain activation plays a critical role in synaptic facilitation and post-tetanic potentiation

“…It was proposed that Ca triggers vesicles mobilization from the reserve pool to the ready-releasable pool and that this process is controlled by synapsins (Humeau et al 2001;Zucker and Regehr 2002;Fioravante et al 2007). Other mechanisms such as modulation of the efficacy of release mechanisms and switching on individual synaptic release sites were also proposed to contribute to PTP (Royer et al 2000;Zhao and Klein 2004;Humeau et al 2007;Korogod et al 2007). …”

“…At excitatory synapses, depletion of the readily releasable vesicle stores by high-frequency stimulation has been recognized as a major cause of short-term synaptic depression (Model et al 1975;Rosenmund and Stevens 1996;Weis et al 1999;Wu and Borst 1999). Inactivation of presynaptic Ca 2+ currents and other downstream mechanisms that lower the release probability were also proposed to account for homosynaptic depression (Patil et al 1998;Wu and Borst 1999;Royer et al 2000;Gover et al 2002;Xu et al 2007). Short-term synaptic enhancement, on the other hand, is attributed to a number of activity-dependent mechanisms including enhanced calcium (Ca) influx (Jackson et al 1991;Geiger and Jonas 2000;Habets and Borst 2005), reduced Ca buffering (Blatow et al 2003;Felmy et al 2003), increased channel-vesicle coupling, or increased Ca sensitivity of the vesicle fusion mechanisms (Korogod et al 2007).…”

Desensitization of Postsynaptic Glutamate Receptors Contributes to High-Frequency Homosynaptic Depression of Aplysia Sensorimotor Connections

“…Stimuli sufficient to elicit withdrawal reflexes evoke a high-frequency burst of spikes in the SNs (Byrne et al 1978a,b;Walters et al 1983;Stopfer and Carew 1996;Frost et al 1997;Antonov et al 1999;Phares et al 2003). Such bursts of SN activity induce homosynaptic depression of the sensorimotor synapses, a mechanism that limits the response of MNs to peripheral stimuli (Byrne et al 1978b;Walters et al 1983;Stopfer and Carew 1996;Antonov et al 1999;Phares et al 2003).For the past thirty years, homosynaptic depression of Aplysia sensorimotor synapses has been attributed exclusively to presynaptic mechanisms Byrne 1982;Gingrich and Byrne 1985;Bailey and Chen 1988;Eliot et al 1994;Armitage and Siegelbaum 1998;Royer et al 2000;Gover et al 2002;Zhao and Klein 2002). Moreover, it has been repeatedly suggested that homosynaptic depression of the sensorimotor synapse does not have a postsynaptic contribution Armitage and Siegelbaum 1998;Royer et al 2000).…”

“…For the past thirty years, homosynaptic depression of Aplysia sensorimotor synapses has been attributed exclusively to presynaptic mechanisms Byrne 1982;Gingrich and Byrne 1985;Bailey and Chen 1988;Eliot et al 1994;Armitage and Siegelbaum 1998;Royer et al 2000;Gover et al 2002;Zhao and Klein 2002). Moreover, it has been repeatedly suggested that homosynaptic depression of the sensorimotor synapse does not have a postsynaptic contribution Armitage and Siegelbaum 1998;Royer et al 2000).…”

“…Moreover, it has been repeatedly suggested that homosynaptic depression of the sensorimotor synapse does not have a postsynaptic contribution Armitage and Siegelbaum 1998;Royer et al 2000).…”