P300 The neuron-synapse dynamics control correlational timescales in the developing visual system
Ruben A. Tikidji-Hamburyan1*, Matthew T. Colonnese1 1School of Medicine. and Health. Sciences, the George Washington Univ., Washington, D.C., USA
*Email: rath@gwu.edu
Introduction: During early development, the retinal spontaneous wave-like activity provides positional (spatial) information, encoded in coarse-grained (>100 ms) inter-neuron spike correlations [1], needed for the refinement of retinothalamic, but also for thalamocortical and intracortical connections. The formation of sub- and cortical networks goes in parallel with the refinement of the retinothalamic connections, therefore, spatial information must be transferred by an unrefined, imprecise thalamic network. Thalamocortical relay neurons (TCs) receive 10 to 20 inputs from neighboring ganglion cells at this age [2,3] , which should cause fast (<100ms) timescale correlations in TCs firing. Here, we model how these correlational timescales are regulated. Methods: TC neurons were simulated as two compartments (dendrosomatic:NaF, KDr, NaP, CaL, CaT, KA, SK, H currents and Ca2+ dynamics and axonal:NaF,KDr) conductance-based model derived from an adult [4]. The parameters were fitted to reproduce the dynamics of mouse TCs recorded at postnatal day 7 (P7) by genetic algorithms with nondominated sorting [5] and with Krayzman’s adaptive multiobjective optimization [6]. The network model consists of 120 TC neurons activated by spikes of retinal ganglion cells (rGCs) recorded ex-vivo at P6-P9. The probability of connections and the synaptic weights are modeled as Gaussian dependence on the distance. Each synapse was modeled by 2-stages: presynaptic depression and postsynaptic NMDAR and AMPAR currents [2,7]. Results: We show that with synaptic convergences observed at P7, either adult neuronal dynamics or synaptic current composition causes fast timescale correlations and a dramatic decrease in spatial information encoded in TC spikes. Therefore, we call them “parasitic” correlations. However, parasitic correlations are suppressed independently of convergence if the model replicates P7 neuronal dynamics and dominance of slow NMDAR currents - the landmark property at this age [3]. Moreover, the interplay between neuron and synaptic dynamics suppresses only parasitic correlation, keeping informative slow timescale correlations intact. In contrast, parasitic correlations are negligible in networks with adult convergence and don’t need to be suppressed. Discussion: Our results suggest that developing neurons regulate their membrane and synaptic dynamics to preserve information critical for proper circuit formation by suppressing non-informative parasitic correlations. As we showed, parasitic correlations can be invariantly suppressed, while informative correlation passes through an unrefined and imprecise network. Our modeling opens critical general questions: how are correlations transferred, and how does a network regulate correlational timescales? The answers to these questions go beyond just neuronal excitability, as for synchrony transferring [8], and require synergetic regulation of both neuronal and synaptic dynamics.
Acknowledgements This work was supported by R01EY022730 and R01NS106244 References ● 10.1523/JNEUROSCI.19-09-03580.1999 ● 10.1002/cne.22223 ● 10.1016/S0896-6273(00)00166-5 ● 10.1371/journal.pcbi.1006753 ● 10.1109/4235.996017 ● 10.7554/eLife.84333 ● 10.1523/JNEUROSCI.4276-07.2008 ● 10.1016/j.neuron.2013.05.030
