Mild Blast Injury Produces Acute Changes in Basal Intracellular Calcium Levels and Activity Patterns in Mouse Hippocampal Neurons

Abstract

Mild traumatic brain injury (mTBI) represents a serious public health concern. Although much is understood about long-term changes in cell signaling and anatomical pathologies associated with mTBI, little is known about acute changes in neuronal function. Using large scale Ca²⁺ imaging in vivo, we characterized the intracellular Ca²⁺ dynamics in thousands of individual hippocampal neurons using a repetitive mild blast injury model in which blasts were directed onto the cranium of unanesthetized mice on two consecutive days. Immediately following each blast event, neurons exhibited two types of changes in Ca²⁺ dynamics at different time scales. One was a reduction in slow Ca²⁺ dynamics that corresponded to shifts in basal intracellular Ca²⁺ levels at a time scale of minutes, suggesting a disruption of biochemical signaling. The second was a reduction in the rates of fast transient Ca²⁺ fluctuations at the sub-second time scale, which are known to be closely linked to neural activity. Interestingly, the blast-induced changes in basal Ca²⁺ levels were independent of the changes in the rates of fast Ca²⁺ transients, suggesting that blasts had heterogeneous effects on different cell populations. Both types of changes recovered after ∼1 h. Together, our results demonstrate that mTBI induced acute, heterogeneous changes in neuronal function, altering intracellular Ca²⁺ dynamics across different time scales, which may contribute to the initiation of longer-term pathologies.