Tail shock produces inhibition as well as sensitization of the siphon-withdrawal reflex of Aplysia: possible behavioral role for presynaptic inhibition mediated by the peptide Phe-Met-Arg-Phe-NH2.

Abstract

Recent studies have shown that, in addition to being modulated by presynaptic facilitation, the sensory neurons of the gill-and siphon-withdrawal reflex ofAplysia are also capable of being modulated by transient presynaptic inhibition produced by the peptide Phe-Met-Arg-Phe-NH2. These two modulatory effects involve different second-messenger systems: the facilitation is mediated through cAMP-dependent protein phosphorylation, and the inhibition is mediated through the lipoxygenase pathway of arachidonic acid. To explore the behavioral function of this inhibition, we have carried out a parametric analysis of the effect of tail shock on the siphon-withdrawal reflex. In addition to producing sensitization of the withdrawal reflex, tail shock also transiently inhibits the reflex. The inhibition is produced by relatively weak shock, whereas sensitization is more prominent and may mask the inhibition with stronger shock. Furthermore, inhibition is not observed after habituation training. Cellular studies suggest that the behavioral inhibition is mediated, at least in part, by presynaptic inhibition of transmitter release from the siphon sensory neurons. Moreover, we have identified an interneuron within the left pleural ganglion (LPL16) that shows Phe-Met-Arg-Phe-NH2 immunoreactivity, is activated by tail shock, and simulates the presynaptic inhibitory actions produced by tail shock. Therefore, our results suggest that presynaptic inhibition mediated by Phe-Met-Arg-Phe-NH2 and its lipoxygenase second messenger contributes to behavioral inhibition of the siphon-withdrawal reflex.Modern studies of the properties of stimuli that serve as reinforcers for sensitization and classical conditioning in vertebrate learning reveal that these stimuli usually have two components, a prominent facilitatory component and a lessobvious inhibitory component. The facilitatory component is important for sensitization and conventional classical conditioning, whereas the inhibitory component is important for conditioned inhibition (1, 2). These dual properties of unconditioned stimuli have also been studied recently in invertebrates (6,14,(20)(21)(22)(23)(24)(25)(26)35). We describe here the existence of an inhibitory component of the unconditioned stimulus for learning in Aplysia and show that this component appears to use Phe-Met-Arg-Phe-NH2 as one of its transmitters.

Multiple Serotonergic Mechanisms Contributing to Sensitization in Aplysia: Evidence of Diverse Serotonin Receptor Subtypes

“…Phe-Met-Arg-Phe-amide (FMRFamide) has been shown to inhibit SN-MN transmission (Mackey et al 1987;Dale and Kandel 1990;Critz et al 1991;Pieroni and Byrne 1992;Sun et al 1996), increase the SN firing threshold (Billy and Walters 1989), and modulate specific postsynaptic MNs involved in defensive reflexes (Belkin and Abrams 1993). However, it is not known whether these peptides are released in the CNS during sensitization training.…”

FMRFamide produces biphasic modulation of the LFS motor neurons in the neural circuit of the siphon withdrawal reflex of Aplysia by activating Na+ and K+ currents

“…and therefore FMRFamide could modulate one neural element in the circuit independently of the others. As described above, Mackey et al (1987) have identified a FMRFamidergic neuron in the pleural ganglion, LPL16, which inhibits the monosynaptic postsynaptic potential between LE siphon sensory neurons and LFS siphon motor neurons. This neuron has presynaptic, but no postsynaptic effects at this synapse (Mackey et al, 1987;Small et al, 1992).…”

“…As described above, Mackey et al (1987) have identified a FMRFamidergic neuron in the pleural ganglion, LPL16, which inhibits the monosynaptic postsynaptic potential between LE siphon sensory neurons and LFS siphon motor neurons. This neuron has presynaptic, but no postsynaptic effects at this synapse (Mackey et al, 1987;Small et al, 1992). Such a pattern of innervation would increase the range of plasticity of which the system is capable, and allow for a greater variety of behavioral outputs.…”

“…In contrast, the results of other investigators indirectly suggest that inhibitory tail shock does modulate the synaptic connections from the siphon sensory neurons. A FMRFamidergic interneuron LPL 16 has been identified that is activated by tail shock, and that causes both narrowing of the sensory neuron action potential and inhibition of the monosynaptic EPSP in the LFS neurons (Mackey et al, 1987;Small et al, 1992). LPL16 apparently does not modulate LFS neurons since activity in this interneuron did not alter the input resistance of the motor neurons (Small et al, 1992).…”

“…5-HT's facilitatory effects on the presynaptic sensory neurons include a decrease in spike threshold, spike broadening, and an increase in transmitter release (Brunelli et al, 1976;Castellucci and Kandel, 1976;Klein and Kandel, 1980;Walters et al, 1983;Klein et al, 1986;Dale and Kandel, 1990). Recently, it has been found that inhibitory inputs also have important modulatory effects on the magnitude of the withdrawal reflex (Mackey et al, 1987;Marcus et al, 1988;Krontiris et al, 1989;Wright et al, 1991;Small et al, 1992;Trudeau and Castellucci, 1992;Fischer and Carew, 1993) and at least one mechanism of behavioral inhibition involves presynaptic modulation of transmitter release from the siphon sensory neurons (Mackey et al, 1987).…”