Deep brain implantable microelectrode arrays for detection and functional localization of the subthalamic nucleus in rats with Parkinson’s disease

The subthalamic nucleus(STN)is considered the best target for deep brain stimulation treatments of Parkinson’s disease(PD).It is difficult to localize the STN due to its small size and deep location.Multichannel microelectrode arrays(MEAs)can rapidly and precisely locate the STN,which is important for precise stimulation.In this paper,16-channel MEAs modified with multiwalled carbon nanotube/poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)(MWCNT/PEDOT:PSS)nanocomposites were designed and fabricated,and the accurate and rapid identification of the STN in PD rats was performed using detection sites distributed at different brain depths.These results showed that nuclei in 6-hydroxydopamine hydrobromide(6-OHDA)-lesioned brains discharged more intensely than those in unlesioned brains.In addition,the MEA simultaneously acquired neural signals from both the STN and the upper or lower boundary nuclei of the STN.Moreover,higher values of spike firing rate,spike amplitude,local field potential(LFP)power,and beta oscillations were detected in the STN of the 6-OHDA-lesioned brain,and may therefore be biomarkers of STN localization.Compared with the STNs of unlesioned brains,the power spectral density of spikes and LFPs synchronously decreased in the delta band and increased in the beta band of 6-OHDA-lesioned brains.This may be a cause of sleep and motor disorders associated with PD.Overall,this work describes a new cellular-level localization and detection method and provides a tool for future studies of deep brain nuclei.

Impaired Spatial Firing Representations of Neurons in the Medial Entorhinal Cortex of the Epileptic Rat Using Microelectrode Arrays

Epilepsy severely impairs the cognitive behavior of patients.It remains unclear whether epilepsy-induced cognitive impairment is associated with neuronal activities in the medial entorhinal cortex(MEC),a region known for its involvement in spatial cognition.To explore this neural mechanism,we recorded the spikes and local field potentials from MEC neurons in lithium-pilocarpine-induced epileptic rats using self-designed microelectrode arrays.Through the open field test,we identified spatial cells exhibiting spatially selective firing properties and assessed their spatial representations in relation to the progression of epilepsy.Meanwhile,we analyzed theta oscillations and theta modulation in both excitatory and inhibitory neurons.Furthermore,we used a novel object recognition test to evaluate changes in spatial cognitive ability of epileptic rats.After the epilepsy modeling,the spatial tuning of various types of spatial cells had suffered a rapid and pronounced damage during the latent period(1 to 5 d).Subsequently,the firing characteristics and theta oscillations were impaired.In the chronic period(>10 d),the performance in the novel object experiment deteriorated.In conclusion,our study demonstrates the detrimental effect on spatial representations and electrophysiological properties of MEC neurons in the epileptic latency,suggesting the potential use of these changes as a"functional biomarker"for predicting cognitive impairment caused by epilepsy.

Detection of neuronal defensive discharge information transmission and characteristics in periaqueductal gray double-subregions using PtNP/PEDOT:PSS modified microelectrode arrays

Threatened animals respond with appropriate defensive behaviors to survive.It has been accepted that midbrain periaqueductal gray(PAG)plays an essential role in the circuitry system and organizes defensive behavioral responses.However,the role and correlation of different PAG subregions in the expression of different defensive behaviors remain largely unexplored.Here,we designed and manufactured a microelectrode array(MEA)to simultaneously detect the activities of dPAG and vPAG neurons in freely behaving rats.To improve the detection performance of the MEAs,PtNP/PEDOT:PSS nanocomposites were modified onto the MEAs.Subsequently,the predator odor was used to induce the rat’s innate fear,and the changes and information transmission in neuronal activities were detected in the dPAG and vPAG.Our results showed that the dPAG and vPAG participated in innate fear,but the activation degree was distinct in different defense behaviors.During flight,neuronal responses were stronger and earlier in the dPAG than the vPAG,while vPAG neurons responded more strongly during freezing.By applying high-performance MEA,it was revealed that neural information spread from the activated dPAG to the weakly activated vPAG.Our research also revealed that dPAG and vPAG neurons exhibited different defensive discharge characteristics,and dPAG neurons participated in the regulation of defense responses with burst-firing patterns.The slow activation and continuous firing of vPAG neurons cooresponded with the regulation of long-term freezing responses.The results demonstrated the important role of PAG neuronal activities in controlling different aspects of defensive behaviors and provided novel insights for investigating defense from the electrophysiological perspective.

Grid cell remapping under three-dimensional object and social landmarks detected by implantable microelectrode arrays for the medial entorhinal cortex

Grid cells with stable hexagonal firing patterns in the medial entorhinal cortex(MEC)carry the vital function of serving as a metric for the surrounding environment.Whether this mechanism processes only spatial information or involves nonspatial information remains elusive.Here,we fabricated an MEC-shaped microelectrode array(MEA)to detect the variation in neural spikes and local field potentials of the MEC when rats forage in a square enclosure with a planar,three-dimensional object and social landmarks in sequence.The results showed that grid cells exhibited rate remapping under social conditions in which spike firing fields closer to the social landmark had a higher firing rate.Furthermore,global remapping showed that hexagonal firing patterns were rotated and scaled when the planar landmark was replaced with object and social landmarks.In addition,when grid cells were activated,the local field potentials were dominated by the theta band(5–8 Hz),and spike phase locking was observed at troughs of theta oscillations.Our results suggest the pattern separation mechanism of grid cells in which the spatial firing structure and firing rate respond to spatial and social information,respectively,which may provide new insights into how the brain creates a cognitive map.

Wireless closed-loop deep brain stimulation using microelectrode array probes

Deep brain stimulation(DBS),including optical stimulation and electrical stimulation,has been demonstrated considerable value in exploring pathological brain activity and developing treatments for neural disorders.Advances in DBS microsystems based on implantable microelectrode array(MEA)probes have opened up new opportunities for closed-loop DBS(CL-DBS)in situ.This technology can be used to detect damaged brain circuits and test the therapeutic potential for modulating the output of these circuits in a variety of diseases simultaneously.Despite the success and rapid utilization of MEA probe-based CL-DBS microsystems,key challenges,including excessive wired communication,need to be urgently resolved.In this review,we considered recent advances in MEA probe-based wireless CL-DBS microsystems and outlined the major issues and promising prospects in this field.This technology has the potential to offer novel therapeutic options for psychiatric disorders in the future.