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...

Endocrine regulation of tissue glucose-6-phosphatase activity in utero was examined by measuring enzyme levels in liver and kidneys of fetal sheep during the second half of gestation and after experimental manipulation of fetal plasma cortisol and insulin levels. Tissue glucose-6-phosphatase activities increased toward term in parallel with the rise in fetal plasma cortisol. At birth, the activities were significantly higher than in utero, but significantly less than in adult nonpregnant sheep. Fetal hypophysectomy lowered fetal plasma cortisol and reduced hepatic and renal glucose-6-phosphatase activities compared with those in intact fetuses near term. Conversely, intrafetal cortisol infusion raised fetal plasma cortisol and significantly increased tissue glucose-6-phosphatase activity to values similar to those in older fetuses. When the data from these groups of fetuses and the newborn lambs were combined, there was a significant positive correlation between the plasma cortisol level and the glucose-6-phosphatase activity in both liver and kidney. Fetal hypoinsulinemia was induced by fasting the ewe for 48 h and by fetal pancreatectomy. Fetal hepatic and renal glucose-6-phosphatase activities were higher in fasted than in fed animals, while pancreatectomy had little apparent effect on enzyme activity in either tissue. However, when differences in plasma cortisol were taken into account, hepatic, but not renal, glucose-6-phosphatase activities were higher in both groups of hypoinsulinemic fetuses than would have been observed in normoinsulinemic animals with a similar plasma cortisol level. Partial correlation analysis of the data showed that plasma insulin and cortisol were both significant influences on hepatic glucose-6-phosphatase activity in utero, but plasma cortisol had the more pronounced effect. Cortisol, therefore, appears to be a physiological regulator of tissue glucose-6-phosphatase activity in utero and enhances the glucogenic capacity of the sheep fetus during late gestation.

We describe here the time course of functional synapse formation and of the development of short-term synaptic plasticity at Aplysia sensorimotor synapses in cell culture, as well as the effects of blocking protein synthesis or postsynaptic receptors on the development of synaptic transmission and plasticity. We find that synaptic responses can be elicited in 50% of sensory neuron-motor neuron pairs by 1 h after cell contact and that short-term homosynaptic depression and synaptic augmentation and restoration by the endogenous facilitatory transmitter serotonin are present at the earliest stages of synapse formation. Neither block of protein synthesis with anisomycin nor block of two types of postsynaptic glutamate receptor has any effect on the development of synaptic transmission or synaptic plasticity. The rapidity of synapse formation and maturation and their independence of protein synthesis suggest that changes in the number of functional synapses could contribute to short- and intermediate-term forms of synaptic plasticity and learning.