We present a high electrode density and high channel count CMOS (complementary metal-oxide-semiconductor) active neural probe containing 1344 neuron sized recording pixels (20 µm × 20 µm) and 12 reference pixels (20 µm × 80 µm), densely packed on a 50 µm thick, 100 µm wide, and 8 mm long shank. The active electrodes or pixels consist of dedicated in-situ circuits for signal source amplification, which are directly located under each electrode. The probe supports the simultaneous recording of all 1356 electrodes with sufficient signal to noise ratio for typical neuroscience applications. For enhanced performance, further noise reduction can be achieved while using half of the electrodes (678). Both of these numbers considerably surpass the state-of-the art active neural probes in both electrode count and number of recording channels. The measured input referred noise in the action potential band is 12.4 µVrms, while using 678 electrodes, with just 3 µW power dissipation per pixel and 45 µW per read-out channel (including data transmission).
Glutamate and γ-aminobutyric acid (GABA) transporters play important roles in balancing excitatory and inhibitory signals in the brain. Increasing evidence suggest that they may act concertedly to regulate extracellular levels of the neurotransmitters. Here we present evidence that glutamate uptake-induced release of GABA from astrocytes has a direct impact on the excitability of pyramidal neurons in the hippocampus. We demonstrate that GABA, synthesized from the polyamine putrescine, is released from astrocytes by the reverse action of glial GABA transporter (GAT) subtypes GAT-2 or GAT-3. GABA release can be prevented by blocking glutamate uptake with the non-transportable inhibitor DHK, confirming that it is the glutamate transporter activity that triggers the reversal of GABA transporters, conceivably by elevating the intracellular Na+ concentration in astrocytes. The released GABA significantly contributes to the tonic inhibition of neurons in a network activity-dependent manner. Blockade of the Glu/GABA exchange mechanism increases the duration of seizure-like events in the low-[Mg2+] in vitro model of epilepsy. Under in vivo conditions the increased GABA release modulates the power of gamma range oscillation in the CA1 region, suggesting that the Glu/GABA exchange mechanism is also functioning in the intact hippocampus under physiological conditions. The results suggest the existence of a novel molecular mechanism by which astrocytes transform glutamatergic excitation into GABAergic inhibition providing an adjustable, in situ negative feedback on the excitability of neurons.
Objective . The extraction and identification of single-unit activities in intracortically recorded electric signals have a key role in basic neuroscience, but also in applied fields, like in the development of high-accuracy brain–computer interfaces. The purpose of this paper is to present our current results on the detection, classification and prediction of neural activities based on multichannel action potential recordings. Approach . Throughout our investigations, a deep learning approach utilizing convolutional neural networks and a combination of recurrent and convolutional neural networks was applied, with the latter used in case of spike detection and the former used for cases of sorting and predicting spiking activities. Main results . In our experience, the algorithms applied prove to be useful in accomplishing the tasks mentioned above: our detector could reach an average recall of 69%, while we achieved an average accuracy of 89% in classifying activities produced by more than 20 distinct neurons. Significance . Our findings support the concept of creating real-time, high-accuracy action potential based BCIs in the future, providing a flexible and robust algorithmic background for further development.
Sleep spindles are a cardinal feature in human NREM sleep and may be important for memory consolidation. We studied the intracortical organization of spindles in men and women by recording spontaneous sleep spindles from different cortical layers using linear microelectrode arrays. Two patterns of spindle generation were identified using visual inspection, and confirmed with factor analysis. Spindles (10–16 Hz) were largest and most common in upper and middle channels, with limited involvement of deep channels. Many spindles were observed in only upper or only middle channels, but approximately half occurred in both. In spindles involving both middle and upper channels, the spindle envelope onset in middle channels led upper by ∼25–50 ms on average. The phase relationship between spindle waves in upper and middle channels varied dynamically within spindle epochs, and across individuals. Current source density analysis demonstrated that upper and middle channel spindles were both generated by an excitatory supragranular current sink while an additional deep source was present for middle channel spindles only. Only middle channel spindles were accompanied by deep low (25–50 Hz) and high (70–170 Hz) gamma activity. These results suggest that upper channel spindles are generated by supragranular pyramids, and middle channel by infragranular. Possibly, middle channel spindles are generated by core thalamocortical afferents, and upper channel by matrix. The concurrence of these patterns could reflect engagement of cortical circuits in the integration of more focal (core) and distributed (matrix) aspects of memory. These results demonstrate that at least two distinct intracortical systems generate human sleep spindles.SIGNIFICANCE STATEMENTBursts of ∼14 Hz oscillations, lasting ∼1 s, have been recognized for over 80 years as cardinal features of mammalian sleep. Recent findings suggest that they play a key role in organizing cortical activity during memory consolidation. We used linear microelectrode arrays to study their intracortical organization in humans. We found that spindles could be divided into two types. One mainly engages upper layers of the cortex, which are considered to be specialized for associative activity. The other engages both upper and middle layers, including those devoted to sensory input. The interaction of these two spindle types may help organize the interaction of sensory and associative aspects of memory consolidation.
Rhythmic slow waves characterize brain electrical activity during natural deep sleep and under anesthesia, reflecting the synchronous membrane potential fluctuations of neurons in the thalamocortical network. Strong evidence indicates that the neocortex plays an important role in the generation of slow wave activity (SWA), however, contributions of individual cortical layers to theSWAgeneration are still unclear. The anatomically correct laminar profiles ofSWAwere revealed under ketamine/xylazine anesthesia, with combined local field potential recordings, multiple‐unit activity (MUA), current source density (CSD) and time‐frequency analyses precisely co‐registered with histology. The up‐state related negative field potential wave showed the largest amplitude in layerIV, theCSDwas largest in layers I andIII, whereasMUAwas maximal in layer V, suggesting spatially dissociated firing and synaptic/transmembrane processes in the rat somatosensory cortex. Up‐state related firing could start in virtually any layers (III–VI) of the cortex, but were most frequently initiated in layer V. However, in a subset of experiments, layerIVwas considerably active in initiating up‐state relatedMUAeven in the absence of somatosensory stimulation. Somatosensory stimulation further strengthened up‐state initiation in layerIV. Our results confirm that cortical layer V firing may have a major contribution to the up‐state generation of ketamine/xylazine‐inducedSWA, however, thalamic influence through the thalamorecipient layerIVcan also play an initiating role, even in the absence of sensory stimulation.