Differential contribution of excitatory and inhibitory neurons in shaping neurovascular coupling in different epileptic neural states.

Understanding the neurovascular coupling (NVC) underlying hemodynamic changes in epilepsy is crucial to properly interpreting functional brain imaging signals associated with epileptic events. However, how excitatory and inhibitory neurons affect vascular responses in different epileptic states remains unknown. We conducted real-time in vivo measurements of cerebral blood flow (CBF), vessel diameter, and excitatory and inhibitory neuronal calcium signals during recurrent focal seizures. During preictal states, decreases in CBF and arteriole diameter were closely related to decreased γ-band local field potential (LFP) power, which was linked to relatively elevated excitatory and reduced inhibitory neuronal activity levels. Notably, this preictal condition was followed by a strengthened ictal event. In particular, the preictal inhibitory activity level was positively correlated with coherent oscillating activity specific to inhibitory neurons. In contrast, ictal states were characterized by elevated synchrony in excitatory neurons. Given these findings, we suggest that excitatory and inhibitory neurons differentially contribute to shaping the ictal and preictal neural states, respectively. Moreover, the preictal vascular activity, alongside with the γ-band, may reflect the relative levels of excitatory and inhibitory neuronal activity, and upcoming ictal activity. Our findings provide useful insights into how perfusion signals of different epileptic states are related in terms of NVC.

Longitudinal study of hemodynamics and dendritic membrane potential changes in the mouse cortex following a soft cranial window installation.

The soft cranial window using polydimethylsiloxane allows direct multiple access to neural tissue during long-term monitoring. However, the chronic effects of soft window installation on the brain have not been fully studied. Here, we investigate the long-term effects of soft window installation on sensory-evoked cerebral hemodynamics and neuronal activity. We monitored the brain tissue immunocytohistology for 6 weeks postinstallation. Heightened reactive astrocytic and microglia levels were found at 2 weeks postinstallation. By 6 weeks postinstallation, mice had expression levels similar to those of normal animals. We recorded sensory-evoked hemodynamics of the barrel cortex and LFP during whisker stimulation at these time points. Animals at 6 weeks postinstallation showed stronger hemodynamic responses and focalized barrel mapping than 2-week postoperative mice. LFP recordings of 6-week postoperative mice also showed higher neural activity at the barrel column corresponding to the stimulated whisker. Furthermore, the expression level of interleukin- 1 ß was highly upregulated at 2 weeks postinstallation. When we treated animals postoperatively with minocycline plus N-acetylcystein, a drug-suppressing inflammatory cytokine, these animals did not show declined hemodynamic responses and neuronal activities. This result suggests that neuroinflammation following soft window installation may alter hemodynamic and neuronal responses upon sensory stimulation.