Changes in hippocampal neuronal activity during and after unilateral selective hippocampal ischemia in vivo.

ABSTRACT

The hippocampal formation is one of the brain regions most sensitive to ischemic damage. However, there are no studies about changes in hippocampal neuronal activity during and after a selective unilateral hippocampal ischemia. We developed a novel unilateral cerebrovascular ischemia model in mice that selectively shuts down blood supply to the ipsilateral hippocampal formation. Using a modified version of the photothrombotic method, we stereotaxically targeted the initial ascending part of the longitudinal hippocampal artery in urethane anesthetized and rose bengal-injected mice. To block blood flow in the targeted artery, we photoactivated the rose bengal by illuminating the longitudinal hippocampal artery through an optical fiber inserted into the brain. In vivo field potential recordings in the CA1 region of the hippocampus before, during and after the induction of ischemia demonstrated a high-frequency discharge (HFD) reaching frequencies of >300 Hz and lasting 7-24 s during the illumination consistent with a massive synchronous neuronal activity. The HFD was invariably followed by a DC voltage shift and a decreased activity at both low (30-57 Hz)- and high (63-119 Hz)-gamma frequencies. This decrease in gamma activity lasted for the entire duration of the recordings (∼160 min) following ischemia. The contralateral hippocampus displayed HFDs but with different frequency spectra and without DC voltage shifts or long-lasting decreases in gamma oscillations. Our findings reveal for the first time the acute effects of unilateral hippocampal ischemia on ensemble hippocampal neuronal activities.