Presynaptic plasticity and associative learning are impaired in a Drosophila presenilin null mutant

Abstract

Alzheimer's disease is a neurodegenerative disorder characterized by progressive memory and cognitive decline that is associated with changes in synaptic plasticity and neuronal cell loss. Recent evidence suggests that some of these defects may be due to a loss of normal presenilin activity. Here, we have examined the effect of loss of Drosophila presenilin (psn) function on synaptic plasticity and learning. Basal transmitter release was elevated in psn mutants while both paired pulse synaptic plasticity and post-tetanic potentiation were impaired. These defects in synaptic strength and plasticity were not due to developmental defects in NMJ morphology. We also found that psn null terminals take up significantly less FM 4-64 than control terminals when loaded with high frequency stimulation, suggesting a defect in synaptic vesicle availability or mobilization. To determine whether these reductions in synaptic plasticity had any impact on learning, we tested the larvae for defects in associative learning. Using both olfactory and visual learning assays, we found that associative learning is impaired in psn mutants compared with controls. Both the learning and synaptic defects could be rescued by expression of a full length psn transgene suggesting the defects are specifically due to a loss of psn function. Taken together, these results provide the first evidence of learning and synaptic defects in a Drosophila psn mutant and strongly suggest a presynaptic role for presenilin in normal neuronal function.

Aversive phototaxic suppression: evaluation of a short‐term memory assay in Drosophila melanogaster

“…Recently, several labs have shown that mutations for genes that model aspects of Alzheimer’s disease are deficient in olfactory conditioning. Deficits have been found in flies carrying an artificial mutation in human amyloid-b-42 , flies mutant for presenilin and flies expressing a wild-type version of the microtubule associated protein Tau ( UAS - Tau wt ), to name a few (Iijima et al 2008; Knight et al 2007; Mershin et al 2004). Interestingly, the learning deficits frequently precede other signs of pathology (Iijima et al 2008; Mershin et al 2004).…”

Equilibrative Nucleoside Transporter 2 Regulates Associative Learning and Synaptic Function inDrosophila

“…To test this possibility, we examined a different form of short-term plasticity, specifically, posttetanic potentiation (PTP). Previous studies have shown that EJP amplitudes are transiently elevated after a brief tetanic stimulation (Zhong and Wu, 1991;Knight et al, 2007). We compared the EJP amplitudes during a 0.2 Hz train of stimuli before and after a brief tetanic stimulation (30 s; 10 Hz).…”

Modeling Presenilin-Dependent Familial Alzheimer's Disease: Emphasis on Presenilin Substrate-Mediated Signaling and Synaptic Function

“…Another group has also observed that PS1 deficiency increases synaptic release and affects the number and docking of synaptic vesicles [69]. It was also shown that basal transmitter release was increased at the neuro-muscular junction in Drosophila lacking PS expression [73]. However, even though basal synaptic transmission seems to be intensified in this later model, synaptic strength and plasticity were impaired after posttetanic potentiation [73].…”

“…It was also shown that basal transmitter release was increased at the neuro-muscular junction in Drosophila lacking PS expression [73]. However, even though basal synaptic transmission seems to be intensified in this later model, synaptic strength and plasticity were impaired after posttetanic potentiation [73]. As a likely consequence, associative learning ability was also impaired.…”