Spontaneous transmitter release is critical for the induction of long-term and intermediate-term facilitation inAplysia

Abstract

Long-term plasticity can differ from short-term in recruiting the growth of new synaptic connections, a process that requires the participation of both the presynaptic and postsynaptic components of the synapse. How does information about synaptic plasticity spread from its site of origin to recruit the other component? The answer to this question is not known in most systems. We have investigated the possible role of spontaneous transmitter release as such a transsynaptic signal. Until recently, relatively little has been known about the functions of spontaneous release. In this paper, we report that spontaneous release is critical for the induction of a learning-related form of synaptic plasticity, long-term facilitation in Aplysia. In addition, we have found that this signaling is engaged quite early, during an intermediate-term stage that is the first stage to involve postsynaptic as well as presynaptic molecular mechanisms. In a companion paper, we show that spontaneous release from the presynaptic neuron acts as an orthograde signal to recruit the postsynaptic mechanisms of intermediate-term facilitation and initiates a cascade that can culminate in synaptic growth with additional stimulation during long-term facilitation. Spontaneous release could make a similar contribution to learning-related synaptic plasticity in mammals.serotonin | cell culture | miniature excitatory postsynaptic current | octopamine | botulinum toxin S pontaneous transmitter release was discovered 60 y ago by Fatt and Katz (1), who found that it represents the quantal unit of transmitter release evoked by a presynaptic action potential. However, until recently, relatively little has been known about other possible functions of spontaneous release. In the last few years, we have learned that spontaneous release can contribute to postsynaptic firing (2, 3), regulation of postsynaptic kinase pathways (4), and maintenance of postsynaptic dendritic spines and receptors (5, 6). Spontaneous release has also been found to contribute to some cases of homeostatic scaling of synaptic strength (7-14). Here we report a role of spontaneous transmitter release in the induction of a learning-related form of synaptic plasticity, longterm facilitation produced by serotonin (5HT) in Aplysia.Long-term plasticity can differ from short-term in recruiting the growth of new synaptic connections, a process that requires the participation of both the presynaptic and postsynaptic components of the synapse (15-21). Because short-term plasticity often involves only one component of the synapse (22-24), the question arises: How does information about synaptic plasticity spread from its site of origin to recruit the other component of the synapse? Studies of synaptic growth during development have revealed a fairly elaborate program of pre-and postsynaptic changes involving a variety of orthograde and retrograde messengers (25), including activity-dependent or spontaneous release of the transmitter itself (26-30). We have now investigated the possible role of spo...

Spontaneous transmitter release recruits postsynaptic mechanisms of long-term and intermediate-term facilitation in Aplysia

“…4B). These results suggest that activation of postsynaptic mGluR5 receptors is critical for the induction of intermediate-term as well as long-term facilitation, supporting the idea that events during the intermediate stage could be first steps in a sequence that can lead to long-term facilitation (10). We therefore decided to focus our analysis on those early events.…”

“…Similarly, injection of BoTx D into the sensory neuron, which reduces spontaneous release and also reduces the postsynaptic increase in IP3 during 10-min 5HT (Fig. 2B), had very little effect on the percent increase in mEPSP frequency (10). These results suggest that the early increase in mEPSP frequency does not depend on postsynaptic mechanisms, and therefore reflects a presynaptic increase in release.…”

“…Because the previous paper suggested that spontaneous transmitter release begins to contribute during an intermediate stage (10), we also investigated postsynaptic receptors that are activated by spontaneous release during intermediate-term facilitation. Similar to long-term facilitation, MPEP (50 μM) reduced intermediate-term facilitation by 10-min 5HT (20 μM, F[1,39] = 10.29, P < 0.01), and a general inhibitor of group I metabotropic glutamate receptors, LY367385 (500 μM), also reduced the facilitation (F = 10.34, P < 0.01 compared with control) (Fig.…”

“…2 A1 and B1). Presynaptic injection of the light chain of botulinum toxin D (BoTx D), which decreases spontaneous release (10), reduced this postsynaptic change (F = 9.45, P < 0.01 compared with vehicle injection). Furthermore, the increase in IP3 occurred throughout the initial segment of the motor neuron but appeared to be larger at sites adjacent to presynaptic varicosities of the sensory neuron ( Fig.…”

“…To examine whether these changes are recruited by spontaneous transmitter release from the presynaptic neuron, we also used two manipulations that act more selectively than 5HT does (10). First, 5HT can stimulate receptors on the postsynaptic as well as presynaptic neuron (3,14).…”