Name
Title | ||
|---|---|---|
Computational modeling of the effects of amyloid-beta on release probability at hippocampal synapses. |
Abstract | ||
|---|---|---|
The role of amyloid beta (A beta) in brain function and in the pathogenesis of Alzheimer's disease (AD) remains elusive. Recent publications reported that an increase in A beta concentration perturbs presynaptic release in hippocampal neurons. In particular, it was shown in vitro that A beta is an endogenous regulator of synaptic transmission at the CA3-CA1 synapse, enhancing its release probability. How this synaptic modulator influences neuronal output during physiological stimulation patterns, such as those elicited in vivo, is still unknown. Using a realistic model of hippocampal CA1 pyramidal neurons, we first implemented this A beta induced enhancement of release probability and validated the model by reproducing the experimental findings. We then demonstrated that this synaptic modification can significantly alter synaptic integration properties in a wide range of physiologically relevant input frequencies (from 5 to 200 Hz). Finally, we used natural input patterns, obtained from CA3 pyramidal neurons in vivo during free exploration of rats in an open field, to investigate the effects of enhanced A beta on synaptic release under physiological conditions. The model shows that the CA1 neuronal response to these natural patterns is altered in the increased-A beta condition, especially for frequencies in the theta and gamma ranges. These results suggest that the perturbation of release probability induced by increased A beta can significantly alter the spike probability of CA1 pyramidal neurons and thus contribute to abnormal hippocampal function during AD. |
Year | DOI | Venue |
|---|---|---|
2013 | 10.3389/fncom.2013.00001 | FRONTIERS IN COMPUTATIONAL NEUROSCIENCE |
Keywords | Field | DocType |
amyloid-beta,hippocampus,computational modeling,release probability,neuronal output | Synapse,Neuroscience,Neurotransmission,Computer science,In vivo,Amyloid beta,Synaptic fatigue,Hippocampal formation,Hippocampus,Stimulation | Journal |
Volume | ISSN | Citations |
7 | 1662-5188 | 3 |
PageRank | References | Authors |
0.50 | 0 | 7 |
Name | Order | Citations | PageRank |
|---|---|---|---|
| Armando Romani | 1 | 3 | 1.17 |
| Cristina Marchetti | 2 | 8 | 1.37 |
| Daniela Bianchi | 3 | 13 | 1.80 |
| Xavier Leinekugel | 4 | 3 | 0.50 |
| Panayiota Poirazi | 5 | 64 | 10.37 |
| M Migliore | 6 | 328 | 52.28 |
| Helene Marie | 7 | 8 | 1.37 |