Reversal of Relative Thresholds for Synaptic Facilitation and Increased Excitability Induced by Serotonin and Tail Nerve Stimulation inAplysiaSensory Neurons

Tail shock induces reflex sensitization inAplysiaand, in parallel, induces a number of modulatory effects in central neurons, such as increased excitability in tail sensory neurons (SNs) and facilitation of synaptic transmission from SNs to motor neurons. Both of these modulatory effects are mimicked by exogenous application of serotonin (5HT) or electrical stimulation of the tail nerve P9. In the present study we examined the activation thresholds for increased excitability and synaptic facilitation induced by either 5HT or P9 stimulation. We found that the concentration of 5HT sufficient to produce a significant increase in excitability produced no significant synaptic facilitation and, conversely, that the intensity of nerve stimulation sufficient to produce significant synaptic facilitation produced no excitability changes. This reversal of relative thresholds for these modulatory effects may reflect the differential access of exogenous 5HT and endogenous 5HT (released by tail nerve stimulation) to the SN cell body and synaptic terminals, respectively.     

Identification of a reinforcement pathway necessary for operant conditioning of head waving in Aplysia californica

The marine mollusc Aplysia californica exhibits a wide range of nonassociative and associative forms of learning. Recently, we found that the learning repertoire of Aplysia includes operant conditioning (Cook & Carew, 1986, 1989b). The behavior we examined is a naturally occurring, side-to-side head-waving response used by Aplysia in seeking food, obtaining a foothold, and egg laying. Aplysia can be operantly conditioned to reduce head-waving to one side of their body if such a response results in exposure to bright uniform-field illumination, which the animals find aversive. An essential step toward achieving a mechanistic understanding of operant conditioning is to identify and characterize the reinforcement pathway used during the learning. Toward this end, we wished to determine which of the peripheral visual pathways in Aplysia are critical for performance of the operant task. Previous experiments indicated that photic input from the optic and rhinophore nerves functionally inhibited motor neurons that participate in the operant response (head-waving), while photic input from the oral veil nerves excited these same motor neurons (Cook & Carew, 1989c). These findings suggested the hypothesis that one or both of these pathways could play an important role in mediating reinforcement during training. To explore this possibility we operantly trained animals that had received chronic bilateral transections of either the optic and rhinophore nerves or the oral veil nerves C1-C3 (in conjunction with transection of the optic and rhinophore nerves). We found that operant conditioning was not disrupted by ablation of input from the eyes and rhinophores. By contrast, ablation of input from the oral veil (together with that from the eyes and rhinophores) abolished operant conditioning. Thus, the oral veil nerves play a critical modulatory role in operant conditioning of head-waving. This observation further suggested that photic input from the oral veil is conveyed to the CNS via the oral veil nerves. In a final experiment we confirmed that stimulation of the oral veil with light evokes increased afferent activity in the oral veil nerves C1-C2. These results support the idea that the oral veil nerves contain processes that are critical components of the reinforcement pathway for operant conditioning of head-waving.     

Delayed-onset sensitization emerges after dishabituation in developing Aplysia.

A recent study of the development of nonassociative learning in the siphon withdrawal reflex of Aplysia showed that dishabituation (facilitation of an habituated response) and sensitization (facilitation of a nonhabituated response) emerge according to different developmental timetables: dishabituation precedes sensitization by approximately 60 days (Rankin & Carew, 1988). Both forms of facilitation of the reflex were observed within 90 s of an electrical shock to the tail. However, more recent work by Marcus and colleagues (1988) in adult animals revealed that sensitization can have a delayed onset of 20-30 min after a strong tail shock. Since the developmental study of Rankin and Carew (1988) only tested the reflex for 10 min after tail shock, it is possible that sensitization was in fact present at earlier developmental stages, but was undetected. To examine this question, in the present study we utilized a longer (40-50 min) post-shock observation period to determine whether delayed-onset sensitization is exhibited in juvenile Aplysia, and if so, when it is expressed during development. In our first experiment, we found that Early Stage 12 juveniles (80-95 days after metamorphosis) showed significant delayed-onset sensitization 30-50 min after a strong tail shock. In a second experiment, we found that delayed-onset sensitization was absent in Stage 11 animals (20-70 days after metamorphosis). Thus delayed-onset sensitization emerges in Early Stage 12. The fact that the birthdate of delayed-onset sensitization is at least 30 days after that of dishabituation (Rankin & Carew, 1987, 1988) supports the hypothesis that these two forms of nonassociative learning may have at least partly different underlying mechanisms.     

Coincident induction of long-term facilitation at sensory-motor synapses in Aplysia: presynaptic and postsynaptic factors

Induction of long-term synaptic changes at one synapse can facilitate the induction of long-term plasticity at another synapse. Here we show that if Aplysia sensory neuron (SN) somata and their remote motor neuron (MN) synapses are simultaneously exposed to serotonin (5HT) pulses, which at either site alone are insufficient to induce long-term facilitation (LTF), processes activated at these sites interact to induce LTF. Coincident induction of LTF requires: (1) that the synaptic pulse occurs within a brief temporal window of the somatic pulse and (2) that local protein synthesis occurs immediately at the synapse, followed by delayed protein synthesis at the soma. LTF at the SN-MN synapses can also be induced with cell-wide application of repeated pulses of 5HT. However, these two forms of LTF differ mechanistically: (1) coincident LTF requires protein synthesis in the postsynaptic motor neuron, whereas repeated 5HT LTF does not, and (2) repeated 5HT LTF is accompanied by intermediate-term (3 h) facilitation, whereas coincident LTF is not. Thus LTF expressed in the same temporal domain can result from different underlying mechanisms.     

Differential role of inhibition in habituation of two independent afferent pathways to a common motor output

Many studies of the neural mechanisms of learning have focused on habituation, a simple form of learning in which a response decrements with repeated stimulation. In the siphon-elicited siphon withdrawal reflex (S-SWR) of the marine mollusk Aplysia, the prevailing view is that homosynaptic depression of primary sensory afferents underlies short-term habituation. Here we examined whether this mechanism is also utilized in habituation of the tail-elicited siphon withdrawal reflex (T-SWR), which is triggered by an independent, polysynaptic afferent pathway that converges onto the same siphon motor neurons (MNs). By using semi-intact preparations in which tail and/or siphon input to siphon MNs could be measured, we found that repeated tail stimuli administered in the presence of a reversible conduction block of the nerves downstream of the tail sensory neurons (SNs) completely abolished the induction of habituation. Subsequent retraining revealed no evidence of savings, indicating that the tail SNs and their immediate interneuronal targets are not the locus of plasticity underlying T-SWR habituation. The networks closely associated with the siphon MNs are modulated by cholinergic inhibition. We next examined the effects of network disinhibition on S-SWR and T-SWR habituation using an Ach receptor antagonist d-tubocurarine. We found that the resulting network disinhibition disrupted T-SWR, but not S-SWR, habituation. Indeed, repeated tail stimulation in the presence of d-tubocurarine resulted in an initial enhancement in responding. Lastly, we tested whether habituation of T-SWR generalized to S-SWR and found that it did not. Collectively, these data indicate that (1) unlike S-SWR, habituation of T-SWR does not involve homosynaptic depression of SNs; and (2) the sensitivity of T-SWR habituation to network disinhibition is consistent with an interneuronal plasticity mechanism that is unique to the T-SWR circuit, since it does not alter S-SWR.     

The tail-elicited tail withdrawal reflex of Aplysia is mediated centrally at tail sensory-motor synapses and exhibits sensitization across multiple temporal domains

The defensive withdrawal reflexes of Aplysia californica have provided powerful behavioral systems for studying the cellular and molecular basis of memory formation. Among these reflexes the tail-elicited tail withdrawal reflex (T-TWR) has been especially useful. In vitro studies examining the monosynaptic circuit for the T-TWR, the tail sensory-motor (SN-MN) synapses, have identified the induction requirements and molecular basis of different temporal phases of synaptic facilitation that underlie sensitization in this system. They have also permitted more recent studies elucidating the role of synaptic and nuclear signaling during synaptic facilitation. Here we report the development of a novel, compartmentalized semi-intact T-TWR preparation that allows examination of the unique contributions of processing in the SN somatic compartment (the pleural ganglion) and the SN-MN synaptic compartment (the pedal ganglion) during the induction of sensitization. Using this preparation we find that the T-TWR is mediated entirely by central connections in the synaptic compartment. Moreover, the reflex is stably expressed for at least 24 h, and can be modified by tail shocks that induce sensitization across multiple temporal domains, as well as direct application of the modulatory neurotransmitter serotonin. This preparation now provides an experimentally powerful system in which to directly examine the unique and combined roles of synaptic and nuclear signaling in different temporal domains of memory formation.     

The roles of MAPK cascades in synaptic plasticity and memory in Aplysia: facilitatory effects and inhibitory constraints

Synaptic plasticity is thought to contribute to memory formation. Serotonin-induced facilitation of sensory-motor (SN-MN) synapses in Aplysia is an extensively studied cellular analog of memory for sensitization. Serotonin, a modulatory neurotransmitter, is released in the CNS during sensitization training, and induces three temporally and mechanistically distinct phases of SN-MN synaptic facilitation. The role of protein kinase A and protein kinase C in SN-MN synaptic facilitation is well documented. Recently, it has become clear that mitogen-activated protein kinase (MAPK) cascades also play a critical role in SN-MN plasticity. Here, we summarize the roles of MAPK cascades in synaptic plasticity and memory for sensitization in Aplysia.     

The impact of exposure to media coverage of the 2012 Paralympic Games on mixed physical ability interactions

The current work assessed the impact of the 2012 Paralympic Games on psychological factors operating during interactions between physically disabled and nondisabled group members. In a two‐wave longitudinal design, the pre‐ to post‐Paralympic increase in exposure to Paralympic media coverage led to more positive in‐group norms about disabled people's competence and improved intergroup contact quality among both physically disabled and nondisabled participants. Moreover, more positive norms about disabled people's competence partially mediated the relationship between media exposure and contact quality. However, exposure to Paralympic media coverage did not appear to impact embarrassment about intergroup contact within either group. Findings are discussed in terms of the efficacy and limitations of Paralympic media coverage to improve intergroup relations in the mixed physical ability context.