Figure 4.

Multiple fragments can be generated in silico by enhanced STD with asynchronous release, NMDA currents, or short-term facilitation

(A) Representative raster plots of spontaneous neuronal network activity of healthy neuronal networks (left) and neuronal networks derived from a patient with Rett syndrome (RTT), measured by Pradeepan et al., (2024).

(B) Example voltage traces recorded at one electrode in the healthy network (top left) or RTT network (top right) during network burst (NB) detections (colored bar below), and example network firing rate traces during the same period (bottom) showing fragments (colored dots).

(C) Representative raster plots of simulated activity with low amounts of asynchronous release (left) and high amounts of asynchronous release (right).

(D) Example voltage traces recorded at one virtual electrode in a simulation with low amounts of asynchronous release (top left) or high amounts of asynchronous release (top right) during NB detections (colored bar below), and example network firing rate traces during the same period (bottom) showing fragments (colored dots).

(E) NB mechanism in simulations with low amounts of asynchronous release: the burst ends because there is not enough asynchronous release to initiate the next fragment when sAHP terminates the NB. (F) NB mechanism in simulations with high amounts of asynchronous release: the firing rate decreases because asynchronous release depletes the amount of available neurotransmitters, but because sAHP is not high enough to terminate the NB and there is enough remaining asynchronous release, the next fragment is initiated, repeating itself until sAHP reaches a threshold.

(G) Top: representative voltage trace recorded at one virtual electrode during a simulation without asynchronous release but with strong NMDA currents and bottom: representative network firing rate trace during the same NB showing multiple fragments.

(H) Mechanism of multiple fragments: a burst fragment is terminated by short-term synaptic depression (STD), but because NMDA channels close slowly and only open when the postsynaptic neuron is depolarized, the NMDA current revives the burst causing the next fragment, repeating itself until the sAHP reaches a threshold.

(I) Top: representative voltage trace recorded at one virtual electrode during a simulation without asynchronous release but with short-term synaptic facilitation (STF) and bottom: representative network firing rate trace during the same NB showing persistent fragments.

(J) Mechanism of multiple fragments: a burst fragment is terminated by STD, but the burst is revived by STF.