  The spontaneous activity pattern of cortical neurons in dissociated culture
is characterized by burst firing that is highly synchronized among a wide
population of cells. The degree of synchrony, however, is excessively higher
than that in cortical tissues. Here, we employed polydimethylsiloxane (PDMS)
elastomers to establish a novel system for culturing neurons on a scaffold with
an elastic modulus resembling brain tissue, and investigated the effect of the
scaffold's elasticity on network activity patterns in cultured rat cortical
neurons. Using whole-cell patch clamp to assess the scaffold effect on the
development of synaptic connections, we found that the amplitude of excitatory
postsynaptic current, as well as the frequency of spontaneous transmissions,
was reduced in neuronal networks grown on an ultrasoft PDMS with an elastic
modulus of 0.5 kPa. Furthermore, the ultrasoft scaffold was found to suppress
neural correlations in the spontaneous activity of the cultured neuronal
network. The dose of GsMTx-4, an antagonist of stretch-activated cation
channels (SACs), required to reduce the generation of the events below 1.0
event/min on PDMS substrates was lower than that for neurons on a glass
substrate. This suggests that the difference in the baseline level of SAC
activation is a molecular mechanism underlying the alteration in neuronal
network activity depending on scaffold stiffness. Our results demonstrate the
potential application of PDMS with biomimetic elasticity as cell-culture
scaffold for bridging the in vivo-in vitro gap in neuronal systems.
