PT  - JOURNAL ARTICLE
AU  - Tapan P. Patel
AU  - Scott C. Ventre
AU  - Donna Geddes-Klein
AU  - Pallab K. Singh
AU  - David F. Meaney
TI  - Single-Neuron NMDA Receptor Phenotype Influences Neuronal Rewiring and Reintegration following Traumatic Injury
AID  - 10.1523/JNEUROSCI.4172-13.2014
DP  - 2014 Mar 19
TA  - The Journal of Neuroscience
PG  - 4200--4213
VI  - 34
IP  - 12
4099  - http://www.jneurosci.org/content/34/12/4200.short
4100  - http://www.jneurosci.org/content/34/12/4200.full
SO  - J. Neurosci.2014 Mar 19; 34
AB  - Alterations in the activity of neural circuits are a common consequence of traumatic brain injury (TBI), but the relationship between single-neuron properties and the aggregate network behavior is not well understood. We recently reported that the GluN2B-containing NMDA receptors (NMDARs) are key in mediating mechanical forces during TBI, and that TBI produces a complex change in the functional connectivity of neuronal networks. Here, we evaluated whether cell-to-cell heterogeneity in the connectivity and aggregate contribution of GluN2B receptors to [Ca2+]i before injury influenced the functional rewiring, spontaneous activity, and network plasticity following injury using primary rat cortical dissociated neurons. We found that the functional connectivity of a neuron to its neighbors, combined with the relative influx of calcium through distinct NMDAR subtypes, together contributed to the individual neuronal response to trauma. Specifically, individual neurons whose [Ca2+]i oscillations were largely due to GluN2B NMDAR activation lost many of their functional targets 1 h following injury. In comparison, neurons with large GluN2A contribution or neurons with high functional connectivity both independently protected against injury-induced loss in connectivity. Mechanistically, we found that traumatic injury resulted in increased uncorrelated network activity, an effect linked to reduction of the voltage-sensitive Mg2+ block of GluN2B-containing NMDARs. This uncorrelated activation of GluN2B subtypes after injury significantly limited the potential for network remodeling in response to a plasticity stimulus. Together, our data suggest that two single-cell characteristics, the aggregate contribution of NMDAR subtypes and the number of functional connections, influence network structure following traumatic injury.