  In vivo, neurons establish functional connections and preserve information
along their synaptic pathways from one information processing stage to the next
in a very efficient manner. Paired spiking (PS) enhancement plays a key role by
acting as a temporal filter that deletes less informative spikes. We analyzed
the spontaneous neural activity evolution in a hippocampal and a cortical
network over several weeks exploring whether the same PS coding mechanism
appears in neuronal cultures as well. We show that self-organized neural in
vitro networks not only develop characteristic bursting activity, but feature
robust in vivo-like PS activity. PS activity formed spatiotemporal patterns
that started at early days in vitro (DIVs) and lasted until the end of the
recording sessions. Initially random-like and sparse PS patterns became robust
after three weeks in vitro (WIVs). They were characterized by a high number of
occurrences and short inter-paired spike intervals (IPSIs). Spatially, the
degree of complexity increased by recruiting new neighboring sites in PS as a
culture matured. Moreover, PS activity participated in establishing functional
connectivity between different sites within the developing network. Employing
transfer entropy (TE) as an information transfer measure, we show that PS
activity is robustly involved in establishing effective connectivities. Spiking
activity at both individual sites and network level robustly followed each PS
within a short time interval. PS may thus be considered a spiking predictor.
These findings suggest that PS activity is preserved in spontaneously active in
vitro networks as part of a robust coding mechanism as encountered in vivo. We
suggest that, presumably in lack of any external sensory stimuli, PS may act as
an internal surrogate stimulus to drive neural activity at different
developmental stages.
