Zika virus encephalitis causes transient reduction of functional cortical connectivity

Area of Science:

• Neuroscience
• Immunology
• Virology

Background:

• Assessing long-term cognitive effects of viral infections like Zika virus (ZIKV) is challenging.
• Functional cortical connectivity offers a potential method to evaluate brain network integrity during and after infection.

Purpose of the Study:

• To investigate the impact of ZIKV encephalitis on functional cortical connectivity using widefield optical imaging.
• To correlate changes in cortical connectivity with synaptic integrity and neuroinflammation during ZIKV infection and recovery.

Main Methods:

• Widefield optical imaging was employed to measure cortical functional connectivity (FC) in mice with ZIKV infection.
• Analysis included assessing neuronal numbers, presynaptic terminals, myeloid cell activation, and cytokine RNA transcription.

Main Results:

• Acute ZIKV infection decreased interhemispheric cortical connectivity and presynaptic terminals, correlating with myeloid cell activation.
• During recovery, synaptic terminals and cortical connectivity were restored, though hippocampal injury and spatial deficits persisted.
• The degree of myeloid cell activation during acute infection predicted synapse and FC recovery.

Conclusions:

• Synaptic integrity in the cortex is crucial for functional brain networks, detectable by widefield optical imaging.
• The immune response and neuroinflammation significantly influence brain network integrity following viral encephalitis.
• While cortical networks show recovery, persistent hippocampal injury suggests complex long-term neurological consequences of ZIKV infection.