Long-term sensitization training primes Aplysia for further learning

Abstract

Repetitive, unilateral stimulation of Aplysia induces long-term sensitization (LTS) of ipsilaterally elicited siphon-withdrawal responses. Whereas some morphological effects of training appear only on ipsilateral sensory neurons, others appear bilaterally. We tested the possibility that contralateral morphological modifications may have functional significance. Therefore, we examined whether LTS training primes subsequent sensitization. Twenty-four hours after LTS training the effects of brief shock treatment (BST) were examined. BST failed to sensitize animals that had previously received either 4-d control treatment or 4-d ipsilateral LTS training. In contrast, BST did sensitize animals that had previously received 4-d contralateral LTS training, suggesting the presence of a latent trace that primes the animal for further learning.The siphon withdrawal reflex of Aplysia is a useful model system for understanding the neurobiology of learning and memory. The reflex exhibits sensitization, a simple form of learning, in which responses elicited by weak test stimuli are augmented by training with strong, usually noxious, stimuli (Carew et al. 1971;Pinsker et al. 1973;Scholz and Byrne 1987). Short-term sensitization (lasting from seconds to minutes) relies on covalent modification of pre-existing proteins. Intermediate-term sensitization (from minutes to hours) requires translation of mRNA into protein but does not require gene transcription. Long-term sensitization (LTS) (lasting days) requires both gene transcription and translation (Sutton et al. 2001). A critical locus of learning-related plasticity is the glutamatergic synapse of sensory neurons onto target motor neurons (Antzoulatos and Byrne 2004). Several experimental observations have suggested that LTS is partly mediated by structural changes of sensory neurons, which maintain sensorimotor synapses in a facilitated state (Bailey and Chen 1983;Wainwright et al. 2002).Twenty-four hours after LTS training on the lateral body wall of intact Aplysia, the siphon withdrawal reflex is sensitized only when evoked by test stimuli on the side of the tail ipsilateral to the trained body wall. When test stimulation is delivered to the contralateral side of the tail, siphon responses are normal (i.e., non-sensitized), similar to the responses of untrained animals (Wainwright et al. 2002). The ipsilateral effect of unilateral training suggests that a critical part of memory may be stored in the ipsilateral pleural-pedal ganglia, that is, the part of the Aplysia central nervous system that mediates the afferent limb of the reflex. Consequently, sensory neurons of only the ipsilateral ganglia would be expected to change after LTS training. Indeed, the number of sensorimotor appositions and the amplitude of sensorimotor excitatory postsynaptic potentials increased only on the ipsilateral side of trained animals. Surprisingly, other structural features of sensory neurons, such as the number of varicosities and the length of neurites, did change on the contralateral side (Wai...

Long-Term Sensitization Training Produces Spike Narrowing inAplysiaSensory Neurons

“…In the subset of trained animals that were tested bilaterally, the responses elicited by tail stimulation on the side ipsilateral to LTS training were significantly longer in duration than the responses elicited by tail stimulation on the contralateral side (Ipsi, 8.93 s Ϯ 1.42; Contra, 5.12 s Ϯ 0.70; t (16) ϭ 3.17; p Ͻ 0.01, t test for paired samples). These data indicate that, as also observed previously (Wainwright et al, 2002(Wainwright et al, , 2004Antzoulatos et al, 2006), this training procedure enhanced the effectiveness of stimulation of ipsilateral sensory neurons to elicit withdrawal responses. Long-term memory for sensitization is presumably mediated by changes of the ipsilateral tail sensory neurons, as well as other downstream sites of the tailelicited siphon withdrawal network (Trudeau and Castellucci, 1992;Cleary et al, 1995).…”

“…Test stimuli consisted of 20 and 200 ms AC shock (60 Hz) provided by a variable transformer for which the output was gated by a relay. As all test and training stimuli used in our study and other studies (Cleary et al, 1998;Wainwright et al, 2002Wainwright et al, , 2004Antzoulatos et al, 2006) were AC (60Hz), the responses of sensory neurons to 60 Hz stimuli is particularly relevant for the animal's behavioral response. The output of the variable transformer passed through a 20 k⍀ resistor to provide a quasiconstant current.…”

“…All experiments were conducted at 15°C. One-sided training of animals for sensitization has been frequently used in the past, because it provides for an additional control within the trained animals (i.e., the contralateral side) (Scholz and Byrne, 1987;Goldsmith and Byrne, 1993;Cleary et al, 1998;Wainwright et al, 2002Wainwright et al, , 2004Antzoulatos et al, 2006). In particular, the 4 d training for LTS has been shown previously to lead to robust electrophysiological and morphological changes in tail sensory neurons (Wainwright et al, 2002(Wainwright et al, , 2004.…”

Defining memories by their distinct molecular traces

“…The initial training session could induce these products and stimulate their transport to the synapse, where they can be used the next day during training to induce morphological changes. This might explain certain priming effects observed during sensitization in Aplysia [22,23]. In cultures, these messages might already be present at the synapse because of the synaptic growth induced by culturing the neurons.…”

“…CIHR Author Manuscript CIHR Author Manuscript [22,23]. In cultures, these messages might already be present at the synapse because of the synaptic growth induced by culturing the neurons.…”