Computational modeling of the effects of amyloid-beta on release probability at hippocampal synapses
Front. Comput. Neurosci.. 2013-01-01; 7:
Lire sur PubMed
1. Front Comput Neurosci. 2013 Jan 25;7:1. doi: 10.3389/fncom.2013.00001.
Computational modeling of the effects of amyloid-beta on release probability at
Romani A(1), Marchetti C, Bianchi D, Leinekugel X, Poirazi P, Migliore M, Marie
(1)Laboratory of Molecular Mechanisms of Synaptic Plasticity, European Brain
Research Institute Rome, Italy.
The role of amyloid beta (Aβ) in brain function and in the pathogenesis of
Alzheimer’s disease (AD) remains elusive. Recent publications reported that an
increase in Aβ concentration perturbs pre-synaptic release in hippocampal
neurons. In particular, it was shown in vitro that Aβ 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 Aβ-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 Aβ on synaptic release under physiological conditions. The model
shows that the CA1 neuronal response to these natural patterns is altered in the
increased-Aβ condition, especially for frequencies in the theta and gamma ranges.
These results suggest that the perturbation of release probability induced by
increased Aβ can significantly alter the spike probability of CA1 pyramidal
neurons and thus contribute to abnormal hippocampal function during AD.