Neuronal avalanche dynamics indicates different universality classes in neuronal cultures.

Neuronal avalanches have become an ubiquitous tool to describe the activity of large neuronal assemblies. The emergence of scale-free statistics with well-defined exponents has led to the belief that the brain might operate near a critical point. Yet not much is known in terms of how the different exponents arise or how robust they are. Using calcium imaging recordings of dissociated neuronal cultures we show that the exponents are not universal, and that significantly different exponents arise with different culture preparations, leading to the existence of different universality classes. Naturally developing cultures show avalanche statistics consistent with those of a mean-field branching process, however, cultures grown in the presence of folic acid metabolites appear to be in a distinct universality class with significantly different critical exponents. Given the increased synaptic density and number of feedback loops in folate reared cultures, our results suggest that network topology plays a leading role in shaping the avalanche dynamics. We also show that for both types of cultures pronounced correlations exist in the sizes of neuronal avalanches indicating size clustering, being much stronger in folate reared cultures.

Inorganic polyphosphate regulates neuronal excitability through modulation of voltage-gated channels.

BACKGROUND: Inorganic polyphosphate (polyP) is a highly charged polyanion capable of interacting with a number of molecular targets. This signaling molecule is released into the extracellular matrix by central astrocytes and by peripheral platelets during inflammation. While the release of polyP is associated with both induction of blood coagulation and astrocyte extracellular signaling, the role of secreted polyP in regulation of neuronal activity remains undefined. Here we test the hypothesis that polyP is an important participant in neuronal signaling. Specifically, we investigate the ability of neurons to release polyP and to induce neuronal firing, and clarify the underlying molecular mechanisms of this process by studying the action of polyP on voltage gated channels. RESULTS: Using patch clamp techniques, and primary hippocampal and dorsal root ganglion cell cultures, we demonstrate that polyP directly influences neuronal activity, inducing action potential generation in both PNS and CNS neurons. Mechanistically, this is accomplished by shifting the voltage sensitivity of NaV channel activation toward the neuronal resting membrane potential, the block KV channels, and the activation of CaV channels. Next, using calcium imaging we found that polyP stimulates an increase in neuronal network activity and induces calcium influx in glial cells. Using in situ DAPI localization and live imaging, we demonstrate that polyP is naturally present in synaptic regions and is released from the neurons upon depolarization. Finally, using a biochemical assay we demonstrate that polyP is present in synaptosomes and can be released upon their membrane depolarization by the addition of potassium chloride. CONCLUSIONS: We conclude that polyP release leads to increased excitability of the neuronal membrane through the modulation of voltage gated ion channels. Together, our data establishes that polyP could function as excitatory neuromodulator in both the PNS and CNS.

High dose folic acid supplementation of rats alters synaptic transmission and seizure susceptibility in offspring.

Maternal folic acid supplementation is essential to reduce the risk of neural tube defects. We hypothesize that high levels of folic acid throughout gestation may produce neural networks more susceptible to seizure in offspring. We hence administered large doses of folic acid to rats before and during gestation and found their offspring had a 42% decrease in their seizure threshold. In vitro, acute application of folic acid or its metabolite 4Hfolate to neurons induced hyper-excitability and bursting. Cultured neuronal networks which develop in the presence of a low concentration (50 nM) of 4Hfolate had reduced capacity to stabilize their network dynamics after a burst of high-frequency activity, and an increase in the frequency of mEPSCs. Networks reared in the presence of the folic acid metabolite 5M4Hfolate developed a spontaneous, distinctive bursting pattern, and both metabolites produced an increase in synaptic density.