Increased transmitter release at excitatory synapses produced by direct activation of adenylate cyclase in rat hippocampal slices

Abstract

The field EPSP recorded in the CA1 region of rat hippocampal slices is potentiated by bath application of the direct adenylate cyclase activator forskolin (Chavez-Noriega and Stevens, 1992a). We have now used the whole-cell patch-clamp technique to analyze the effect of forskolin on evoked synaptic currents and on spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs) recorded in rat hippocampal slices in order to determine the relative contributions of pre- and postsynaptic mechanisms to this increased synaptic strength. Application of 50 microM forskolin in the presence of 3-isobutyl-1-methylxanthine (IBMX; a phosphodiesterase inhibitor) enhanced the evoked EPSC (eEPSC) peak amplitude to 230 +/- 43% of control (n = 13). No significant change in sEPSC or in mEPSC amplitude was detected after forskolin addition (106 +/- 7%, n = 9), indicating that postsynaptic receptor sensitivity at synaptic junctions is not greatly affected. In contrast, a large increase in sEPSC and mEPSC frequency was noted in all cells (299 +/- 81%). Following forskolin application, the amplitude distribution of evoked synaptic currents shifted to larger values, but more significantly, a sharp decrease in failure rate was produced in all cells tested. Also, a significant correlation was found between the potentiation produced by forskolin in IBMX on the eEPSC and the ratio of the squared coefficient of variation (CV = SD/mean). Finally, a quantal analysis of four cells was consistent with the hypothesis that transmitter release was increased by forskolin/IBMX with, if anything, a concomitant decrease in quantal size. Together, these observations indicate that presynaptic mechanisms significantly contribute to the enhancement produced by this diterpene.(ABSTRACT TRUNCATED AT 250 WORDS)

Serotonergic Modulation of GABAergic and Glutamatergic Synaptic Transmission in Mechanically Isolated Rat Medial Preoptic Area Neurons

“…But in the present study, modulation of GABAergic transmission occurred independent of Ca 2 + (Figure 3), which is consistent with studies of presynaptic inhibition in the hippocampus (Scanziani et al, 1992;Thompson et al, 1993). Activation of the AC-cAMP signal-transduction pathway directly facilitates presynaptic neurotransmitter release in rat central neurons (Chavez-Noriega and Stevens, 1994;Chen and Regehr, 1997;Capogna et al, 1995;Trudeau et al, 1996). The proteins synapsin I and II, which are active in the vesicular release process, are phosphorylated by cAMPdependent kinase, and synapsin phosphorylation increases the number of synaptic vesicles in the releasable pool (Greengard et al, 1993).…”

γ-Aminobutyric acid type A receptors modulate cAMP-mediated long-term potentiation and long-term depression at monosynaptic CA3–CA1 synapses

“…Activation of the cAMP cascade enhances evoked and spontaneous release of neurotransmitter in Schaffer͞commissural terminals in CA1 of acute hippocampal slices (29), as indicated by a significant increase in frequency of miniature excitatory postsynaptic currents. Quantal analysis of unitary synaptic transmission between CA3-CA1 synapses also suggests that the cAMP-induced late phase of LTP involve an increase in the number of quanta released in response to a single presynaptic action potential (20).…”

Muscarinic stimulation of synaptic activity by protein kinase C is inhibited by adenosine in cultured hippocampal neurons

“…In addition, Munc-18, myristoylated alanine-rich C kinase substrate (MARCKS), soluble NSF attachment proteins (SNAP-25), and ␣-SNAP can be phosphorylated by PKC (41-44). Interestingly, protein kinase A activation can also lead to facilitation of transmitter release in hippocampal cells (29,45) by directly increasing the probability of exocytosis (46). Again, this presynaptic effect is independent of changes in [Ca 2ϩ ] i (46).…”