%0 Journal Article
%T Computational modeling of the effects of amyloid-beta on release probability at hippocampal synapses
%A Armando Romani
%A Cristina Marchetti
%A Daniela Bianchi
%A Xavier Leinekugel
%A Panayiota Poirazi
%A Michele Migliore
%A H¨¦l¨¨ne Marie
%J Frontiers in Computational Neuroscience
%D 2013
%I Frontiers Media
%R 10.3389/fncom.2013.00001
%X The role of amyloid beta (A¦Â) in brain function and in the pathogenesis of Alzheimer's disease (AD) remains elusive. Recent publications reported that an increase in A¦Â concentration perturbs pre-synaptic release in hippocampal neurons. In particular, it was shown in vitro that A¦Â 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¦Â-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¦Â on synaptic release under physiological conditions. The model shows that the CA1 neuronal response to these natural patterns is altered in the increased-A¦Â condition, especially for frequencies in the theta and gamma ranges. These results suggest that the perturbation of release probability induced by increased A¦Â can significantly alter the spike probability of CA1 pyramidal neurons and thus contribute to abnormal hippocampal function during AD.
%K amyloid-beta
%K hippocampus
%K computational modeling
%K release probability
%K neuronal output
%U http://www.frontiersin.org/Journal/10.3389/fncom.2013.00001/abstract