In vivo imaging of neuronal calcium during electrode implantation: Spatial and temporal mapping of damage and recovery

Abstract

Implantable electrode devices enable long-term electrophysiological recordings for brain-machine interfaces and basic neuroscience research. Implantation of these devices, however, leads to neuronal damage and progressive neural degeneration that can lead to device failure. The present study uses in vivo two-photon microscopy to study the calcium activity and morphology of neurons before, during, and one month after electrode implantation to determine how implantation trauma injures neurons. We show that implantation leads to prolonged, elevated calcium levels in neurons within 150 μm of the electrode interface. These neurons show signs of mechanical distortion and mechanoporation after implantation, suggesting that calcium influx is related to mechanical trauma. Further, calcium-laden neurites develop signs of axonal injury at 1-3 h post-insert. Over the first month after implantation, physiological neuronal calcium activity increases, suggesting that neurons may be recovering. By defining the mechanisms of neuron damage after electrode implantation, our results suggest new directions for therapies to improve electrode longevity.

In vivo microstimulation with cathodic and anodic asymmetric waveforms modulates spatiotemporal calcium dynamics in cortical neuropil and pyramidal neurons of male mice

“…In fact, even increasing the duration of the return phase can reduce the tissue safety [70]. We have observed gas bubble formation under two-photon imaging when stimulating beyond the normal safety limits (indicative of the potential exceeding the water window) [40]; no gas bubble formation was observed in the present study; however, other irreversible reactions could have occurred [70]. Because stimulation waveform has the potential to improve spatial selectivity of neuronal activation it will be important to evaluate the safety of these waveforms for both electrode and tissue damage.…”

“…Subjects (n = 5-6 biological replicates) were housed in 12h light/dark cycles with free access to food and water. Acute surgery and electrode implantation followed a protocol previously published [24,[40][41][42][43][44][45][46][47][48][49]. Mice were initially anesthetized with ketamine/xylazine (75mg/kg;7mg/kg) intraperitoneally (IP) and updated with ketamine (40 mg/kg) as needed (~ every hour).…”

Enhanced Cerebral Blood Volume under Normobaric Hyperoxia in the J20-hAPP Mouse Model of Alzheimer’s Disease

“…In our acute experimental sessions, the intactness of NVC was masked by the technical procedure used and a mismatch between neural activity and haemodynamic response was recorded ( Figure S2). As described briefly 9 , insertion of an electrode into the mouse brain can cause cortical spreading depression (CSD) to occur across the cortex 29 . CSD is characterised by prolonged vasoconstriction that can persist for some time (in some cases over an hour) and this generally dampens haemodynamic responses and overall cerebral blood flow across a wide area of the cerebral cortex 30 .…”

The role of oligodendrocytes and their progenitors on neural interface technology: A novel perspective on tissue regeneration and repair

“…Indeed, vascular pericytes, which promote angiogenesis through the release of VEGFs and MMPs, have been observed near implanted electrodes [26, 142, 143]. Insertion causes dimpling of the surface of the brain, displacing and compressing cells and blood vessels, and can persist for hours after insertion [10, 19, 144–146]. Increased strain has been correlated with increased cell death in neurons and astrocytes as well as production of IL-1β via ERK signaling pathways in astrocytes [147–149].…”

“…Insertion of a microelectrode array into the brain induces cortical spreading depression in neurons, a global calcium activating event that can lead to neuronal injury and cell death [265]. Although the impact of CSDs on oligodendrocytes and their precursors are unknown, spreading depolarizations in the cortex are accompanied by glutamate-induced excitotoxic events that can be detrimental to oligodendrocyte viability [266].…”