Abstract
Multielectrodes have been used with great success to simultaneously record the activity of neuronal populations in awake, behaving animals. In particular, there is great promise in the use of this technique to allow the control of neuroprosthetic devices by human patients. However, it is crucial to fully characterize the tissue response to the chronic implants in animal models ahead of the initiation of human clinical trials. Here we evaluated the effects of unilateral multielectrode implants on the motor cortex of rats weekly recorded for 1–6 months using several histological methods to assess metabolic markers, inflammatory response, immediate-early gene (IEG) expression, cytoskeletal integrity and apoptotic profiles. We also investigated the correlations between each of these features and firing rates, to estimate the impact of post-implant time on neuronal recordings. Overall, limited neuronal loss and glial activation were observed on the implanted sites. Reactivity to enzymatic metabolic markers and IEG expression were not significantly different between implanted and non-implanted hemispheres. Multielectrode recordings remained viable for up to 6 months after implantation, and firing rates correlated well to the histochemical and immunohistochemical markers. Altogether, our results indicate that chronic tungsten multielectrode implants do not substantially alter the histological and functional integrity of target sites in the cerebral cortex.
Highlights
The use of chronic multielectrodes for recording the activity of neuronal populations in awake behaving animals [1,2,3,4,5,6] represented a great step forward in our understanding of the function of the brain
Electrophysiology On average, 72621 neuronal units per session were chronically recorded in each animal
Waveforms from 72 neuronal units recorded 1 month after array implantation are illustrated in the top left panel of Figure 1A, with a decay of around 45% of units recorded after 3 months and around 85% after 6 months (1 month: 72621; 3 months: 39611; 6 months: 1163.2; mean6SD)
Summary
The use of chronic multielectrodes for recording the activity of neuronal populations in awake behaving animals [1,2,3,4,5,6] represented a great step forward in our understanding of the function of the brain. An important prerequisite for any invasive brain machine interface is to maintain a stable signal in the CNS for the longest time possible without causing either structural, cellular or metabolic changes capable of compromising the device’s performance and/or resulting in tissue degeneration around the implanted electrode [15] For this reason, laboratories around the world have tested different materials and designs for microwire arrays in rodents [16,17], non-human primates [14,18,19] and humans [20]. The local activation of glial cells due to chronic electrode implants usually causes electrode encapsulation [28], and the resulting increase in electrical impedance of the recording tip over time [29] This process presumably leads to an initial improvement of extracellular signal’s selectivity, followed by a progressive decrease in the number of recorded neurons, until the complete cessation of signal [29]
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