Withdrawal Reflexes In Aplysia Research Articles

Sensitization of the gill and siphon withdrawal reflex of Aplysia: multiple sites of change in the neuronal network

1. Recent studies have emphasized the major contribution of interneuronal transmission to the mediation and learning-associated modulation of the gill and siphon withdrawal (GSW) reflex of Aplysia. We wish to provide more direct support for the hypothesis that inhibitory junctions are crucial sites of plasticity. 2. In parallel experiments we investigated modulation at five major sites of synaptic transmission in the GSW network: 1) from sensory neurons to motor neurons, 2) from sensory neurons to excitatory interneurons (INTs+) 3) from INTs+ to motor neurons (MNs), 4) from inhibitory interneurons (INTs-) to INTs+, and 5) from INTs+ to INTs-. 3. While recording simultaneously from a single sensory neuron of the LE cluster, an INT+, and a MN, we found that both LE-MN and LE-INTs+ synapses were facilitated by the activation of modulator neurons by stimulation of the left pleuroabdominal connective (185 and 93%, respectively) as well as by serotonin (5-HT) (191 and 84%). Junctions of the second type were therefore less facilitated. The difference in the magnitude of facilitation at these two sites is an indication of a branch-specific, differential efficacy in the modulation of different central synapses made by a single neuron. 4. Although INT(+)-MN junctions have the capacity to display marked posttetanic potentiation, they are not significantly potentiated after connective stimulation. Sensitization of the GSW reflex is therefore not necessarily accompanied by a modification of transmission at these synapses. 5. Inhibitory transmission to INTs+ is significantly reduced by connective stimulation (36%) and by 5-HT (71%). This supports the hypothesis that a reduction of feedback inhibition into INTs+ is a major mechanism of reflex sensitization and may account for the increased evoked firing of INTs+ that is observed after connective stimulation. 6. The excitatory input to INTs- is selectively decreased by 5-HT (50%) and by the molluscan neuropeptide small cardioactive peptide B (38%). This latter effect, which could produce disinhibition of INTs+, may explain the previous observation that this peptide is able to potentiate the evoked input to MNs of the reflex at a concentration (1 microM) that fails to modify monosynaptic sensory-motor transmission. 7. These results indicate that transmission through a small neuronal network that mediates a withdrawal reflex in Aplysia may be modulated at multiple sites and by different mechanisms. These mechanisms include: 1) branch-specific facilitation of sensory neuron outputs and 2) inhibition of INT(-)-INT+ inhibitory postsynaptic potentials by endogenous modulatory neurons and by 5-HT.(ABSTRACT TRUNCATED AT 400 WORDS)

Modulation of IK,Ca by phorbol ester-mediated activation of PKC in pleural sensory neurons of Aplysia.

1. The electrophysiological properties of the sensory neurons that mediate withdrawal reflexes in Aplysia are modulated by a number of second messengers. For example, the second messengers adenosine 3',5'-cyclic monophosphate (cAMP) and arachidonic acid modulate the S-K+ current (IK,S) and the calcium-activated K+ current (IK,Ca). Recent evidence suggests that protein kinase C (PKC) may also be an important regulator of cellular plasticity. In the present study we examined the possibility that IK,Ca was modulated by the activation of PKC in the pleural sensory neurons. 2. In voltage-clamped sensory neurons the application of phorbol esters, such as phorbol dibutyrate (PDBu), phorbol myristate (PMA), and phorbol diacetate (PDAc), which activate PKC, caused a dose-dependent increase in a voltage-dependent current with properties that resembled IK,Ca. The inactive isomer of phorbol ester, 4 alpha-phorbol, was without effect. 3. This phorbol ester-sensitive current had the kinetics and pharmacological sensitivity of IK,Ca. The current developed slowly during step depolarizations, showed little inactivation, and was activated at membrane potentials greater than approximately 0 mV. In addition, the current modulated by phorbol esters was blocked by a concentration of tetraethylammonium (TEA) that blocks a component of IK,Ca in the sensory neurons. 4. IK,Ca, which was activated directly by the iontophoretic injection of Ca2+, was also enhanced by PDBu. Moreover, the enhancement of Ca(2+)-elicited responses by PDBu persisted after Ca2+ influx was blocked by cobalt. These results indicate that at least one component of the modulation of IK,Ca by PDBu was independent of the modulation of voltage-dependent Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Reversal of synaptic depression by serotonin at Aplysia sensory neuron synapses involves activation of adenylyl cyclase.

Facilitation of the monosynaptic connection between siphon sensory neurons and gill and siphon motor neuron contributes to sensitization and dishabituation of the gill and siphon withdrawal reflex in Aplysia. The facilitatory transmitter serotonin (5-HT) initiates two mechanisms that act in parallel to increase transmitter release from siphon sensory neurons. 5-HT acts, at least partly through cAMP, to broaden the presynaptic action potential. 5-HT also initiates a second process that facilitates depressed sensory neuron synapses by a mechanism independent of changes in action potential duration. Recent experiments indicated that either of two protein kinases, cAMP-dependent protein kinase A and protein kinase C, are capable of effectively activating this second facilitatory mechanism, restoring synaptic transmission in depressed synapses. We have used the adenylyl cyclase inhibitor SQ 22,536 [9-(tetrahydro-2-furyl)adenine or THFA] to explore the contribution of cAMP to the reversal of synaptic depression. THFA effectively inhibited both adenylyl cyclase activity in vitro and known cyclase-mediated effects in intact sensory neurons. THFA also completely blocked facilitation of depressed synapses by 5-HT. These results suggest that adenylyl cyclase plays a critical role in the reversal of synaptic depression that contributes to dishabituation in this system.

Morphological Aspects of Synaptic Plasticity in Aplysia An Anatomical Substrate for Long‐Term Memorya

The morphological basis of long-term sensitization of the gill-and-siphon withdrawal reflex in Aplysia was explored by examining the structure of identified sensory neuron synapses in control and behaviorally modified animals. Following long-term training, sensitized animals displayed an increase in the number of sensory neuron synapses compared to control animals. The relative permanence of these structural changes and their similarity in time course to the behavioral duration of sensitization suggest a role for synapse number changes during long-term memory.

Injection of the cAMP-responsive element into the nucleus of Aplysia sensory neurons blocks long-term facilitation

In both vertebrates and invertebrates, long-term memory differs from short-term in requiring protein synthesis during training. Studies of the gill and siphon withdrawal reflex in Aplysia indicate that similar requirements can be demonstrated at the level of sensory and motor neurons which may participate in memory storage. A single application of serotonin, a transmitter that mediates sensitization, to individual sensory and motor cells in dissociated cell cultures leads to enhanced transmitter release from the sensory neurons that is independent of new macromolecular synthesis. Five applications of serotonin cause a long-term enhancement, lasting one or more days, which requires translation and transcription. Prolonged application or intracellular injection into the sensory neuron of cyclic AMP, a second messenger for the action of serotonin, also produce long-term increases in synaptic strength, suggesting that some of the gene products important for long-term facilitation are cAMP-inducible. In eukaryotic cells, most cAMP-inducible genes so far studied are activated by the cAMP-dependent protein kinase (A kinase), which phosphorylates transcription factors that bind the cAMP-responsive element TGACGTCA. The cAMP-responsive element (CRE) binds a protein dimer of relative molecular mass 43,000, the CRE-binding protein (CREBP), which has been purified and shown to increase transcription when phosphorylated by the A kinase. Here we show that extracts of the Aplysia central nervous system and extracts of sensory neurons contain a set of proteins, including one with properties similar to mammalian CREBPs, that specifically bind the mammalian CRE sequence. Microinjection of the CRE sequence into the nucleus of a sensory neuron selectively blocks the serotonin-induced long-term increase in synaptic strength, without affecting short-term facilitation. Taken together, these observations suggest that one or more CREB-like transcriptional activators are required for long-term facilitation.

Developmental analysis in Aplysia reveals inhibitory as well as facilitatory effects of tail shock.

Recent studies that were performed to examine the development of learning in the siphon withdrawal reflex in Aplysia have shown that habituation, dishabituation, and sensitization emerge according to different developmental timetables. In the course of those studies, an inhibitory process triggered by tail shock was also described. In this study we examined some of the features of this inhibitory process in young juvenile animals (stage 11 and early stage 12) which developmentally lack sensitization

Long-term heterosynaptic inhibition in Aplysia.

Synaptic transmission between mechanosensory and motor neurons of the gill withdrawal reflex in Aplysia can undergo both short-term and long-term modulation. One form of short-term synaptic depression lasting minutes can be evoked by the peptide Phe-Met-Arg-Phe-amide (FMRFamide), and is mediated by the lipoxygenase pathway of arachidonic acid. We report here using cell culture, that the same monosynaptic sensory-to-motor component of the gill withdrawal reflex can also undergo long-term synaptic depression lasting 24 h after five applications of FMRFamide over a 2-h period. The long-term depression evoked by FMRFamide is transmitter-specific. Dopamine or low-frequency stimulation of sensory neurons, which also produce short-lasting synaptic depression in vivo, failed to evoke a long-term change. As is the case for long-term presynaptic facilitation of this connection with serotonin, the long-term depression, but not the short-term, can be blocked when applications of FMRFamide are given in the presence of anisomycin, a reversible inhibitor of protein synthesis. Thus, heterosynaptic depression parallels heterosynaptic facilitation in having a long-term as well as a short-term form, and in both cases the long-term modulation requires the synthesis of gene products not essential for the short-term changes.

Modulation of calcium current and diverse K+ currents in identified Hermissenda neurons by small cardioactive peptide B

The molluscan neuropeptides, small cardioactive peptides A and B (SCPA,B), are known to modulate the responses of many molluscan central and peripheral target cells (see review by Lloyd, 1986), but their full range of physiological actions remains unknown. External application of SCPB (1-10 microM) modified diverse ionic conductances in a set of giant identifiable neurons in the brain of the marine mollusk Hermissenda crassicornis. SCPB caused a transient depolarization and increased input resistance that enhanced or promoted cell firing. Under voltage-clamp, SCPB reduced a "background" residual current (IR), reduced early transient K+ current (IA), reduced a delayed K+ current (IK(V], and enhanced ICa, IBa, and a Ca2+-activated K+ current, IK(Ca). In tetraethylammonium chloride (TEA) saline, SCPB enhanced the amplitude and duration and reduced the threshold of evoked Ca and Ba spikes. Immunocytochemical staining techniques have localized an endogenous SCPB-like peptide in numerous somata and their neurites in the nervous system of Hermissenda (Longley and Longley, 1985; Watson and Willows, 1986). These data are consistent with a role for SCPB as a neurotransmitter/neurohormone modulator of neuronal excitability in Hermissenda. A neurotransmitter role for endogenous SCPs has been proposed for a synaptic pair of cultured neurons in the Aplysia buccal ganglion (Lloyd et al., 1986). SCPB has been implicated in the control of feeding motor output in Aplysia (Sossin et al., 1986) and Tritonia (Willows and Watson, 1986), and in the presynaptic facilitation of sensory neurons mediating the gill and siphon defensive withdrawal reflex in Aplysia (Abrams et al., 1984).

Dishabituation and sensitization emerge as separate processes during development in Aplysia

Until recently, dishabituation and sensitization have commonly been considered to reflect a unitary process: Sensitization refers to a general facilitation produced by strong or noxious stimuli that enhances subsequent responding; dishabituation has been thought to represent a special instance of sensitization in which the facilitation is simply superimposed on a habituated response level. The unitary process hypothesis was based on the observation that both decremented and nondecremented responses are facilitated by a common noxious or strong stimulus. However, this observation does not rule out the possibility that dishabituation and sensitization could reflect separate processes that are activated in parallel by a strong stimulus. Recent cellular experiments by Hochner et al. (1986) suggest that this, in fact, occurs in the sensory neurons of the gill withdrawal reflex in Aplysia. A developmental analysis of learning in the marine mollusc Aplysia permits a direct behavioral test of this hypothesis. If dishabituation and sensitization reflect a unitary process then they should emerge at the same time ontogenetically. On the other hand, if they reflect different processes, then they might emerge according to different ontogenetic timetables. In the present study we examined the temporal emergence of dishabituation and sensitization in the defensive siphon withdrawal reflex in 3 stages of juvenile Aplysia: stage 11, early stage 12, and late stage 12. Animals received one of 2 kinds of training: Dishabituation training, in which the effect of strong tail shock on habituated responses were observed, and Sensitization training, in which the effect of strong tail shock on nondecremented responses was observed. We found that, while dishabituation was present in all stages examined, sensitization did not emerge until several weeks later, in late stage 12. These results were confirmed and extended in a group of animals that were tested twice: first in stage 11, when they showed no sensitization, and again 13 weeks later, in late stage 12, when they then showed significant sensitization. Our analysis of nondecremented responses prior to the emergence of sensitization also revealed an unexpected inhibitory component of tail shock that produces reflex depression. Moreover, there was a clear progression in the net effects of tail shock during development: reflex depression was produced in stages 11 and early stage 12, followed by a transition to reflex facilitation (sensitization) in late stage 12. Finally, when sensitization emerged in late stage 12, the process of dishabituation showed a significant increase compared with previous developmental stages.(ABSTRACT TRUNCATED AT 400 WORDS)

Single-cell neuronal model for associative learning.

Recently, a novel cellular mechanism, activity-dependent neuromodulation, was identified in sensory neurons mediating the gill and tail withdrawal reflexes in Aplysia. This mechanism may explain associative learning on a behavioral level. The present study was designed to mathematically model subcellular events that may underlie this mechanism and to examine the ability of the model to fit available empirical data. In this associative model, the reinforcing or unconditioned stimulus (US) leads to non-specific enhancement of transmitter release from sensory neurons by activating a cAMP cascade. Spike activity in sensory neurons, the conditioned stimulus (CS), transiently elevates intracellular Ca2+. The CS-triggered increases of intracellular Ca2+ "primes" the cyclase and amplifies the US-mediated cAMP synthesis. As a result of pairing specific amplification of cAMP levels, transmitter release is enhanced beyond that produced by unpaired stimuli or by application of the US alone. The model is capable of fitting empirical data on activity-dependent neuromodulation and predicts a characteristic interstimulus interval (ISI) curve. At the subcellular level, the model's ISI function is related to the time course of the buffering of intracellular Ca2+. The magnitude and duration of the pairing specific enhancement of transmitter release is related to the levels and time course of intracellular cAMP stimulation.

Quantitative analysis of the relation between gill amplitude and siphon duration in the defensive withdrawal reflex of Aplysia.

The defensive withdrawal reflex of the mantle organs (gill, siphon, and mantle shelf) of the marine mollusc Aplysia californica has been the subject of numerous studies investigating the cellular and molecular mechanisms of learning. In behavioral experiments, the reflex has been monitored by means of two different response measures, either siphon duration (in unrestrained, freely moving animals) or gill amplitude (in restrained preparations). It has generally been assumed that one component of the reflex provides a reliable index of the other. In the present study, we directly tested this assumption by simultaneously measuring both response parameters in the same experiment. Reflex response magnitude was varied in two ways: (a) by systematically varying stimulus intensity, and (b) by holding the stimulus intensity constant, but delivering stimuli at a rate that produced significant habituation. Using both measures we found that gill amplitude and siphon duration were highly correlated (average correlation = .90). Thus our data show that either response measure can serve as a reliable estimate of the overall reflex response.

A critical period for macromolecular synthesis in long-term heterosynaptic facilitation in Aplysia.

Both long-term and short-term sensitization of the gill and siphon withdrawal reflex in Aplysia involve facilitation of the monosynaptic connections between the sensory and motor neurons. To analyze the relationship between these two forms of synaptic facilitation at the cellular and molecular level, this monosynaptic sensorimotor component of the gill-withdrawal reflex of Aplysia can be reconstituted in dissociated cell culture. Whereas one brief application of 1 microM serotonin produced short-term facilitation in the sensorimotor connection that lasted minutes, five applications over 1.5 hours resulted in long-term facilitation that lasted more than 24 hours. Inhibitors of protein synthesis or RNA synthesis selectively blocked long-term facilitation, but not short-term facilitation, indicating that long-term facilitation requires the expression of gene products not essential for short-term facilitation. Moreover, the inhibitors only blocked long-term facilitation when given during the serotonin applications; the inhibitors did not block the facilitation when given either before or after serotonin application. These results parallel those for behavioral performance in vertebrates and indicate that the critical time window characteristic of the requirement for macromolecular synthesis in long-term heterosynaptic facilitation is not a property of complex circuitry, but an intrinsic characteristic of specific nerve cells and synaptic connections involved in the long-term storage of information.

Facilitatory transmitters and cAMP can modulate accommodation as well as transmitter release in Aplysia sensory neurons: Evidence for parallel processing in a single cell

Presynaptic facilitation of transmission from sensory to motor neurons contributes significantly to behavioral sensitization of defensive withdrawal reflexes in Aplysia. Presynaptic facilitation is associated with a decrease in the serotonin-sensitive K(+) conductance. This decrease broadens the presynaptic action potential. In addition, the procedures that cause facilitation-stimulation of the connective (the pathway from the tail and head), application of modulatory transmitters, or injection of cAMP-also increase the excitability of the sensory neurons as tested with intracellular depolarizing pulses injected into the cell body. The increased excitability is reflected in a decreased threshold for generating action potentials and a reduction in accommodation to prolonged constant current stimuli. By influencing the excitability of the peripheral processes of the sensory neurons, stimulation of the connectives or serotonin also produces a small enhancement of the response of the sensory neurons to a tactile stimulus applied to the siphon. The excitability changes appear to result, at least in part, from the same cellular mechanisms that lead to broadening of the action potential, a cAMP-mediated closure of K(+) channels. Therefore, these findings indicate that the same class of mechanisms can, in principle, have a dual action and provide further evidence for parallel processing in the modulation of transmitter release from a single neuron.

Stimuli that produce sensitization lead to elevation of cyclic AMP levels in tail sensory neurons of Aplysia

Facilitation of synaptic connections between sensory neurons and motor neurons mediating the tail withdrawal reflex in Aplysia is produced by the modulatory effects of sensitizing stimuli. Facilitation can be mimicked by perfusing these neurons with serotonin (5-HT) in a semi-intact preparation. Consequently, 5-HT has been presumed to be acting as an agonist of the modulatory transmitter that mediates sensitizing input in vivo. While the 5-HT effects appear to be mediated by increased cyclic adenosine monophosphate (cAMP) levels in the sensory neurons, a critical issue that has not been examined is whether sensitizing stimuli also increase cAMP levels in these cells. We now report that such sensitizing stimuli delivered to the tail of a semi-intact preparation lead to elevation of cAMP levels in the tail sensory neurons.

Monosynaptic connections made by the sensory neurons of the gill- and siphon-withdrawal reflex in Aplysia participate in the storage of long-term memory for sensitization

We have found that in the gill- and siphon- withdrawal reflex of Aplysia, the memory for short-term sensitization grades smoothly into long-term memory with increased amounts of sensitization training. One cellular locus for the storage of the memory underlying short-term sensitization is the set of monosynaptic connections between the siphon sensory cells and the gill and siphon motor neurons. We have now also found that these same monosynaptic connections participate in the storage of the memory underlying long-term Sensitization. We examined the amplitudes of the direct synaptic connections produced by siphon sensory neurons on the gill motor neuron L7 in nervous systems removed from control and from long-term sensitized animals 1 day after the end of long-term sensitization training. The connections were significantly larger in long-term sensitized animals than in control animals. The finding that long-term memory occurs at the same synaptic locus as the short-term memory should facilitate study of the cellular and molecular mechanisms involved in the conversion of short-term to long-term memory.

Activity-dependent presynaptic facilitation: an associative mechanism in Aplysia.

In studying the classical conditioning of the siphon withdrawal reflex in Aplysia, we have identified a neuronal mechanism that plays an important role in this conditioning: activity-dependent presynaptic facilitation. This review describes our analysis of the cellular basis of this associative mechanism. During the conditioning of the withdrawal reflex, the unconditioned stimulus, a tail shock, produces presynaptic facilitation of synaptic transmission from the siphon sensory neurons in the conditioned stimulus pathway. The facilitation is enhanced if a sensory neuron has fired action potentials just prior to receiving facilitatory input, as occurs during training when the conditioned stimulus precedes the unconditioned stimulus. This activity-dependent enhancement of presynaptic facilitation provides a mechanism for the temporal specificity in conditioning of the reflex. Activity-dependent facilitation appears to involve the same cyclic AMP (cAMP)-dependent cascade that underlies presynaptic facilitation in these neurons in the absence of paired spike activity. Our evidence suggests that it is the transient elevation of intracellular Ca2+ that is responsible for the enhancement of the facilitation response by paired spike activity. Moreover, our preliminary results indicate that Ca2+/calmodulin is able to potentiate the activation of adenylate cyclase in Aplysia neurons by facilitatory transmitter. Thus, the dual activation of the calmodulin-dependent cyclase by Ca2+ and transmitter may give this enzyme an important associative role in learning. In the conclusion, the possible phylogenetic generality of this associative mechanism is discussed as well as its possible role in activity-dependent processes in neuronal development.

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.

We have found that two endogenous neuropeptides in Aplysia, the small cardioactive peptides SCPA and SCPB, facilitate synaptic transmission from siphon mechano-sensory 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. All 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.

A cellular mechanism of classical conditioning in Aplysia: activity-dependent amplification of presynaptic facilitation.

A training procedure analogous to differential classical conditioning produces differential facilitation of excitatory postsynaptic potentials (EPSP's) in the neuronal circuit for the siphon withdrawal reflex in Aplysia. Thus, tail shock (the unconditioned stimulus) produces greater facilitation of the monosynaptic EPSP from a siphon sensory neuron to a siphon motor neuron if the shock is preceded by spike activity in the sensory neuron than if the shock and spike activity occur in a specifically unpaired pattern or if the shock occurs alone. Further experiments indicate that this activity-dependent amplification of facilitation is presynaptic in origin and involves a differential increase in spike duration and thus in Ca2+ influx in paired versus unpaired sensory neurons. The results of these cellular experiments are quantitatively similar to the results of behavioral experiments with the same protocol and parameters, suggesting that activity-dependent amplification of presynaptic facilitation may make a significant contribution to classical conditioning of the withdrawal reflex.

Facilitatory transmitter causes a selective and prolonged increase in adenosine 3':5'-monophosphate in sensory neurons mediating the gill and siphon withdrawal reflex in Aplysia

Sensitization of the gill and siphon withdrawal reflex in the marine mollusc, Aplysia california, is a simple form of learning Underlying this behavioral changes is a cascade of biochemical events. The first step in this cascade is postulated to be an increase in cAMP within the sensory neurons of the abdominal ganglion. We have developed a labeling protocol with 32Pi which permits us to measure the synthesis of cAMP within a single sensory neurons. Application of serotonin for 5 min was found to triple the content of [32P]cAMP in sensory neurons. The response is specific to serotonin: dopamine, a transmitter that does not produce sensitization, did not increase cAMP. Physiological stimulation of facilitator neurons also resulted in a 3.5-fold increase of cAMP in sensory neurons but not in other cells of the ganglion. We studied the time course of the increase of cAMP in sensory cells stimulated with serotonin and found that it parallels closely the time course of the short term form of presynaptic facilitation. We also have determined the effects of transmitters on the synthesis of cAMP in other identified neurons of the ganglion. The bag cells responded specifically to serotonin. R15, which has been shown to be hyperpolarized both the serotonin and by dopamine, responded to both transmitters by increased synthesis synthesis of cAMP. Thus, the dopamine- and serotonin-sensitive cyclase can be localized to both the same and different cells. Other cells did not respond to serotonin or to dopamine, indicating that a transmitter-sensitive adenylate cyclase is a specific property and is not present in all neurons.

Sensitization in Aplysia : Restoration of Transmission in Synapses Inactivated by Long-Term Habituation

Long-term habituation of a simple withdrawal reflex in Aplysia leads to an inactivation of synaptic transmission between identified sensory and gill motor neurons that persists for more than 3 weeks. A single sensitizing stimulus rapidly reactivates both the depressed behavioral response and the inactivated synaptic transmission. Thus sensitization, a simple competitive form of learning, provides a mechanism whereby changing environmental demands can rapidly override the long-term memory of habituation.