Two endogenous neuropeptides modulate the gill and siphon withdrawal reflex in Aplysia by presynaptic facilitation involving cAMP-dependent closure of a serotonin-sensitive potassium channel.

Abstract

We have found that two endogenous neuropeptides in Aplysia, the small cardioactive peptides SCPA and SCPB, facilitate synaptic transmission from siphon mechanosensory neurons and enhance the defensive withdrawal reflex that these sensory neurons mediate. Single-channel recording revealed that these peptides close a specific K+ channel, the S channel, which is sensitive to cAMP. Moreover, the peptides increase cAMP levels in these sensory neurons. This reduction in K+ current slows the repolarization of the action potential in these cells, which increases transmitter release. In these actions, the SCPs resemble both noxious sensitizing stimuli, which enhance the reflex, and serotonin. Bioassay of HPLC fractions of abdominal ganglion extracts and immunocytochemistry indicate that both the SCPs and serotonin are present in the ganglion and are found in processes close to the siphon sensory neurons, suggesting that these transmitters may be involved in behavioral sensitization. Recent evidence suggests that one group of identified facilitatory interneurons, the L29 cells, does not appear to contain either the SCPs or serotonin but may use yet another facilitatory transmitter.Thus, it appears that several transmitters can converge to produce presynaptic facilitation in the sensory neurons of the defensive withdrawal reflex. AU of the transmitters studied here, the SCPs and serotonin, act via an identical molecular cascade: cAMP-dependent closure of the S-K' channel, broadening of the presynaptic action potential, and facilitation of transmitter release.Peptide transmitters have been a focus of interest in neurobiology because they often have modulatory effects on behavior (1). However, it has only rarely been possible to relate the behavioral action of a neuropeptide to its cellular action on specific nerve cells (2-4, 38). We here report that two molluscan neuropeptides increase the gain of the gill and siphon withdrawal reflex of Aplysia by presynaptically facilitating transmission from the sensory neurons of the reflex pathway. By combining single-channel and biochemical analyses, we have found that this facilitation involves the cAMP-mediated closure of a specific K+ channel, the recently described S channel (5).This defensive withdrawal reflex in Aplysia is enhanced during two simple forms of learning: sensitization and classical conditioning (6,7). In each case, a noxious stimulus produces presynaptic facilitation of synaptic transmission from the afferent neurons in the reflex, the mechanosensory neurons in the abdominal ganglion that innervate the siphon, to interneurons and motoneurons (8, 9). Although application of serotonin to the abdominal ganglion stimulates the facilitatory actions of noxious stimuli (10,11), there is now evidence from the immunocytochemical studies of Ono and McCaman (12) and Kistler et al. (13) that at least one set of facilitatory interneurons, the L29 cells (14), is not serotonergic. Thus transmitters other than serotonin are involved in sensitization. We were therefore ...

Long-term memory consolidation: The role of RNA-binding proteins with prion-like domains

“…24 Formation of short term or long term memory is mirrored by short-term or long-term facilitation (increased neurotransmitter release) from sensory neurons that mediate touch onto motor neuron synapses that mediate a withdrawal response. 15,25 This facilitation of neurotransmitter release is mediated by shock-triggered serotonin that induces cAMP signaling and resultant PKA activation in presynaptic endings of sensory neurons. 26 Both short-term (STF) and long-term facilitation (LTF) can be reconstituted in synapses formed in primary cultures composed exclusively of dissected sensory and motor neurons.…”

Switching Off and On of Synaptic Sites atAplysiaSensorimotor Synapses

“…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 et al, 1976; Castellucci and Kandel, 1976;Abrams et al, 1984). These and other forms of synaptic modulation in the intact nervous system can be reconstituted in cultures with a single sensory neuron contacting a single motor neuron (Schacher et al, 1990;Klein, 1993Klein, , 1994Lin and Glanzman, 1994).…”

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

“…[These two populations of sensory neurons have similar physiological properties, including their responses to FMRFamide (Abrams et al, 1984;Belardetti et al, 1987;Piomelli et al, 1987) and to the facilitatory transmitters 5-HT (Klein and Kandel, 1980;Bemier et al, 1982;Klein et al, 1982;Walters et al, 1983;Ocorr and Byrne, 1985;Pollock et al, 1985) and the small cardioactive neuropeptides SCP, and SCP, (Abrams et al, 1984;Ocorr and Byrne, 1985;Pieroni and Byrne, 1992;Jarrard et al, 1993).] FMRFamide causes an increase in spike threshold ofthe sensory neurons, narrowing of the sensory neuron action potential (Abrams et al, 1984;Pieroni and Byrne, 1992), and a decrease in the sensory neuron-to-motor neuron excitatory PSP (Abrams et al, 1984;Piomelli et al, 1987). FMRFamide has direct effects on transmitter release, causing a reduction in spontaneous release from sensory neurons .…”