Abstract
Influenza virus infection is one of common infectious diseases occurring worldwide. The human influenza virus can infect the central nervous system and cause brain dysfunctions affecting cognition and spatial memory. It has been previously shown that infection with the influenza viral protein within the hippocampus decreases Ca2+ influx and reduces excitatory postsynaptic currents. However, the neuronal properties of animals surviving neonatal infection have not been investigated. Using a mouse model of neonatal influenza infection, we performed thorough electrophysiological analyses of hippocampal neurotransmission. We found that animals surviving the infection exhibited reduced spontaneous transmission with no significant defects in evoked neurotransmission. Interestingly, the hippocampus of the infected group conducted synaptic transmission with less fidelity upon repeated stimulations and failed to generate action potentials faithfully upon step current injections primarily due to reduced Na+ influx. The reversal potential for the Na+ current was hyperpolarized and the activation of Na+ channels was slower in the infected group while the inactivation process was minimally disturbed. Taken together, our observations suggest that neonatally infected offsprings exhibit noticeable deficits at rest and severe failures when higher activity is required. This study provides insight into understanding the cellular mechanisms of influenza infection-associated functional changes in the brain.
Highlights
Serotonin and glutamate receptor expression in the frontal cortex[16]
When two consecutive stimulations were given in a pair with a very short time interval (50 ms), we observed no significant changes in the ratio of the amplitude of the two evoked EPSCs (eEPSCs) evoked by each stimulation between the control and neonatally infected animals (Fig. 2A, p > 0.8)
We found no significant difference in the ratio of AMPAR- vs. NMDAR-mediated eEPSCs, suggesting no primary postsynaptic deficits upon neonatal influenza infection (Fig. 2B, p > 0 .2)
Summary
Previous studies have suggested that influenza virus infection induces abnormalities in synaptic function[19,20,21]. The transduction of viral nucleoproteins (NP) into primary hippocampal neurons as well as influenza infection have been shown to decrease spontaneous excitatory activity and reduce Ca2+ currents in cultured hippocampal neurons[19,20]. We aimed to examine functional changes in the hippocampus at the synaptic level upon influenza infection by taking advantage of a mouse model of neonatal H1N1 viral infection[25]. We observed that the activation of the Na+ channels was slower and the reversal potential of the Na+ currents was hyperpolarized in the infected group, which could lead to deficits in brain function after neonatal influenza infection. Our results provide useful insight into the influenza infection-associated functional changes that have been observed in previous studies
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