Presynaptic effectors contributing to cAMP-induced synaptic potentiation in Drosophila.

cAMP analogs and activation of adenylyl cyclase by forskolin strongly potentiate synaptic transmission at the Drosophila neuromuscular junction. These effects are generally attributed to activation of cAMP-dependent protein kinase. Recent reports on crustacean and mammalian synapses have implicated other cAMP-dependent effectors in synaptic potentiation. Drosophila neuromuscular junctions were tested for effects of two known cAMP-dependent effectors: hyperpolarization-activated, cyclic nucleotide-regulated channels (HCNCs) and guanine nucleotide exchange protein activated by cAMP (Epac). Forskolin-induced enhancement of synaptic transmission was drastically reduced by a blocker of HCNCs, but not completely eliminated. A specific agonist for Epac modestly enhanced synaptic potentials. This agonist also stabilized their amplitudes in the presence of a blocker of HCNCs. The observations implicate HCNCs and Epac in cAMP-dependent potentiation that does not require cAMP-dependent protein kinase, indicating that additional previously unexplored factors contribute to synaptic plasticity in Drosophila. Genetic and molecular techniques available for Drosophila can be used to define the underlying molecular basis for cAMP-dependent synaptic potentiation.

Drosophila larval neuromuscular junction's responses to reduction of cAMP in the nervous system.

We investigated the effects of chronically lowered cyclic adenosine monophosphate (cAMP) on the morphology and physiology of the Drosophila larval neuromuscular junction, using two fly lines in which cAMP was significantly lower than normal in the nervous system: (a) transgenic flies in which the dunce (dnc) gene product was overexpressed in the nervous system, and (b) flies mutant for the rutabaga gene (rut1) which have reduced adenylyl cyclase activity. In comparison with controls, larvae with reduced cAMP exhibited a smaller number of synaptic varicosities. This effect was more pronounced in transgenic larvae, in which the reduction of neural cAMP was more pronounced. Synaptic transmission was also reduced in both cases, as evidenced by smaller excitatory junctional potentials (EJPs). Synaptic currents recorded from individual synaptic varicosities of the neuromuscular junction indicated almost normal transmitter release properties in transgenic larvae and a modest impairment in rut1 larvae. Thus, reduction in EJP amplitude in transgenic larvae is primarily due to reduced innervation, while in rut1 larvae it is attributable to the combined effects of reduced innervation and a mild impairment of transmitter release. We conclude that the major effect of chronically lowered cAMP is reduction of innervation rather than impairment of transmitter release properties.

Cycloheximide blocks the retention of maternal experience in postpartum rats.

Two studies were done to determine the effects of cycloheximide (CYX), a protein synthesis inhibitor, on maternal experience effects in rats. In the first study eight groups received a 2-h maternal experience 36 h after cesarean (c)-section and two groups received no post c-section experience. Among the experienced groups, two received icv injections of CYX or saline (SAL) 30 min before the maternal experience, two received CYX or SAL 10 min after the experience, and two received the injections 24 h after the experience. One inexperienced group received CYX and the other received SAL 36 h after c-section. Tests for maternal behavior occurred 10 days after c-section. CYX was not able to block or disrupt the "acquisition" or expression of ongoing maternal behavior during the 2-h experience phase. However, CYX was able to block the long-term "retention" of a 2-h maternal experience if the drug was present during or immediately after the experience, prior to "consolidation." The second study investigated the effects of CYX administered immediately after the maternal experience on the expression and retention of maternal behavior 4 and 6 days after c-section, to determine whether the hormonally mediated short-onset latencies of the 4-day group would be blocked by CYX. Eight groups of animals were tested for maternal behavior. Four were tested 4 days after c-section and four were tested 6 days after c-section. Within each of these groups two were experienced and two inexperienced; within each experience condition one group received CYX and one received SAL. Day 4 groups exhibited shorter onset latencies than Day 6 groups. There was also a CYX-SAL difference in maternal onset latencies among experienced Day 6 groups but not among Day 4 groups. These data indicate that the blocking effects of CYX can be seen only when hormonal priming of maternal behavior is no longer in evidence.

Effects of maternal hormones on 'timidity' and attraction to pup-related odors in female rats.

The present study was designed to determine whether changes in 'emotionality' and responses to odorants that occur in the postpartum rat are due to the same configuration of hormones that facilitate the expression of maternal behavior. Ovariectomized females were implanted with silastic capsules containing progesterone and estradiol or cholesterol for a 19-21 day period and were tested 1 or 7 days later for emergence behavior, ambulation in the open-field and responses to nesting-material containing different odorants. All females were given two tests in which clean nest-material was presented and two with lactating nest material. In comparison to cholesterol animals hormonally primed animals emerged more rapidly into the open-field, crossed more squares while in the field and spent more time around the odor stimulus. Moreover, hormonally primed animals crossed more squares in the region around the odor source when lactating nest odor was present than when it was not and, under the lactating nest odor condition, crossed more squares in the stimulus region than did any other group. This study suggests that the Bridges' regimen of progesterone and estradiol reduces general 'timidity,' reflected in open-field performance, and increases attraction to pup-related odors. These hormone-induced behavioral changes may well contribute to the heightened maternal responsiveness also produced by these hormones.