A reliable method for intracranial electrode implantation and chronic electrical stimulation in the mouse brain

Abstract

BackgroundElectrical stimulation of brain structures has been widely used in rodent models for kindling or modeling deep brain stimulation used clinically. This requires surgical implantation of intracranial electrodes and subsequent chronic stimulation in individual animals for several weeks. Anchoring screws and dental acrylic have long been used to secure implanted intracranial electrodes in rats. However, such an approach is limited when carried out in mouse models as the thin mouse skull may not be strong enough to accommodate the anchoring screws. We describe here a screw-free, glue-based method for implanting bipolar stimulating electrodes in the mouse brain and validate this method in a mouse model of hippocampal electrical kindling.MethodsMale C57 black mice (initial ages of 6–8 months) were used in the present experiments. Bipolar electrodes were implanted bilaterally in the hippocampal CA3 area for electrical stimulation and electroencephalographic recordings. The electrodes were secured onto the skull via glue and dental acrylic but without anchoring screws. A daily stimulation protocol was used to induce electrographic discharges and motor seizures. The locations of implanted electrodes were verified by hippocampal electrographic activities and later histological assessments.ResultsUsing the glue-based implantation method, we implanted bilateral bipolar electrodes in 25 mice. Electrographic discharges and motor seizures were successfully induced via hippocampal electrical kindling. Importantly, no animal encountered infection in the implanted area or a loss of implanted electrodes after 4–6 months of repetitive stimulation/recording.ConclusionWe suggest that the glue-based, screw-free method is reliable for chronic brain stimulation and high-quality electroencephalographic recordings in mice. The technical aspects described this study may help future studies in mouse models.

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“…Two electrodes were placed in the medial hole onto the dura surface near the retrosplenial cortex, and the third electrode was placed in the lateral hole for ground. The electrodes were secured to the skull as described elsewhere (Jeffrey et al, 2013). After 7 days of recovery, ECoG recordings were made with a DP-311 differential amplifier (Warner Instruments, Hamden, CT) with high-pass/low-pass filters set at 0.1 and 300 Hz and digitized/recorded (Digidata 1400, pClamp 10; Molecular Devices, Sunnyvale, CA).…”

A novel combinational approach of microstimulation and bioluminescence imaging to study the mechanisms of action of cerebral electrical stimulation in mice

“…() and Jeffrey et al . (), for which a cranial window was created using cyanoacrylate glue or acrylic resin to anchor the electrodes and the electric pins to the skull (Jeffrey et al . ; Halpern et al .…”

“…() and Jeffrey et al . (), the electrical pins connecting the electrodes to the external stimulator are located directly above them, interposing between the scanner and the brain. To avoid this problem, we replaced the electrical pins by connectors that we placed at the rear of the skull, above the cerebellum (Fig.…”

Effects of neonatal hypoxic-ischemic episodes on late seizure outcomes in C57 black mice

“…Power spectral plots were generated by averaging with 50% window overlap and a spectral resolution of 0.3 Hz. EEG spikes were considered if they displayed amplitudes of ≥6 times of standard deviations of background EEG signals and base durations of 30-70 ms (Jeffrey et al, 2013;Lang et al, 2014). To determine the dominant frequency of the hippocampal theta rhythm, spectral plots were generated from 10-s EEG segments in individual mice during the period of movement or exploration behaviors.…”

“…Electrode implantation, EEG recordings and analysis were done as previously described (El-Hayek et al, 2011;Jeffrey et al, 2013Jeffrey et al, , 2014. Both post-HI and sham control animals received electrode implantation at 2-3 months of age.…”