0 ± 11.8, n = 22, ApNLG overexpression + 5-HT 46.4 ± 14.6, n = 23, ApNLG mutant overexpression+ 5-HT 4.3 ± 12.9, n = 23, p < 0.001 versus ApNLG overexpression + 5-HT). Overexpression of wild-type

ApNLG or ApNLG mutant had no effect on basal transmission (% initial EPSP amplitude: no expression 3.5 ± 7.0, n = 21; ApNLG mutant overexpression alone –6.8 ± 8.9, n = 9; ApNLG overexpression alone –9.3 ± 7.0, n = 17). Previous studies of the sensory-to-motor neuron synapse in Aplysia have revealed the existence of an intermediate-term phase of facilitation that requires protein synthesis Ruxolitinib molecular weight but does not require nuclear transcription ( Ghirardi et al., 1995 and Sutton and Carew, 2000). We therefore wondered whether the ApNLG autism-linked mutant might also have an effect on intermediate-term facilitation as

it precedes LTF and may serve to initiate the transsynaptic signaling required for the long-term process. Indeed, we found that similar to its affect on LTF, there this website was a significant decrease in facilitation during the intermediate-term time domain measured at 1 hr after repeated pulses of 5-HT when the ApNLG autism-linked mutant was overexpressed in the postsynaptic motor neuron ( Figure 8A, % initial EPSP amplitude: 5-HT 74.4 ± 11.7, n = 22, ApNLG overexpression + 5-HT 76.2 ± 13.0, n = 23, ApNLG mutant overexpression+ 5-HT 24.8 ± 10.9, n = 23, p < 0.05 versus ApNLG overexpression + 5-HT). Overexpression of wild-type ApNLG or ApNLG mutant had no effect on basal transmission measured at 1 hr (% initial EPSP amplitude: no expression 7.1 ± 4.3, n = 21; ApNLG mutant overexpression alone 1.8 ± 9.1, n = 9; ApNLG overexpression alone 5.8 ± 4.3, n = 17). The findings that the ApNLG autism-linked mutant blocks both intermediate-term and long-term facilitation indicate that the transsynaptic interaction mediated by neurexin and neuroligin is a critical component of both memory phases and is essential for the normal progression of long-term memory storage. To investigate the role of the neurexin-neuroligin transsynaptic interaction in activity-dependent

synaptic plasticity, we have cloned Aplysia homologs of not neurexin (ApNRX) and neuroligin (ApNLG). We found that they are indeed necessary components of 5-HT-induced long-term facilitation and the associated presynaptic structural remodeling and growth of sensory-to-motor neuron synapses of the Aplysia gill-withdrawal reflex reconstituted in culture. The presence of neurexin and neuroligin in Aplysia as well as in the genomes of Drosophila and C. elegans further supports the view that the neurexin-neuroligin transsynaptic interaction is highly conserved throughout evolution ( Tabuchi and Südhof, 2002). Like other invertebrates, ApNRX has a domain structure similar to that of vertebrate α-neurexin with the likely absence of β-neurexin-like isoforms.