GABA, not glutamate, controls the activity of substantia nigra reticulata neurons in awake, unrestrained rats

Substantia nigra pars reticulata (SNr) receives both GABAergic and glutamatergic (GLU) inputs that are believed to act together to regulate neuronal activity in this structure. To examine the role of these inputs, single-unit recording was coupled with iontophoresis of GLU and GABA in rats under two conditions: awake, unrestrained and under chloral hydrate anesthesia. Although GABA potently inhibited SNr cells in both conditions, freely moving rats showed lower sensitivity than anesthetized animals. Likewise, GLU effectively induced excitations in most SNr neurons in anesthetized animals but was much less effective in awake, unrestrained animals in terms of both the number of sensitive cells and the magnitude of GLU-induced excitation. These findings, along with consistent excitations induced by bicuculline in awake, unrestrained rats, suggest that modulation of GABA inhibitory input, not the opposing actions of GLU and GABA, is the primary factor that regulates the activity state of SNr neurons

Pallidal origin of GABA release within the substantia nigra pars reticulata during high-frequency stimulation of the subthalamic nucleus

High-frequency stimulation of the subthalamic nucleus (HFS-STN) is an effective treatment for alleviating the motor symptoms of parkinsonian patients. However, the neurochemical basis of its effects remains unknown. We showed previously that 1 h of HFS-STN in normal rats increases extracellular glutamate (Glu) level in the output nuclei of the STN, the globus pallidus (GP), and the substantia nigra pars reticulata (SNr), consistent with an increase in the activity of STN neurons. HFS-STN also increases GABA levels in the SNr, but the origin of this increase is unclear. We investigated the effectiveness of HFS-STN for improving Parkinson's disease symptoms, using intracerebral microdialysis to determine the extracellular Glu and GABA levels of the GP and SNr in response to HFS-STN in anesthetized hemiparkinsonian rats [6-hydroxydopamine lesion of the substantia nigra pars compacta (SNc)]. Basal levels of Glu and GABA in the GP and SNr were significantly higher in hemiparkinsonian than in intact rats. HFS-STN did not affect extracellular Glu level in the SNr of hemiparkinsonian rats but doubled the level of GABA. Ibotenic acid lesion of the GP abolished the increase in GABA levels in the SNr induced by HFS-STN in SNc-lesioned rats. These results provide neurochemical confirmation of the hyperactivity of the STN after dopaminergic denervation and suggest that the therapeutic effects of HFS-STN may result partly from the stimulation of pallidonigral fibers, thereby revealing a potential role for pallidal GABA in the inhibition of basal ganglial output structures during HFS-STN

Action Potential Waveform Variability Limits Multi-Unit Separation in Freely Behaving Rats

Extracellular multi-unit recording is a widely used technique to study spontaneous and evoked neuronal activity in awake behaving animals. These recordings are done using either single-wire or mulitwire electrodes such as tetrodes. In this study we have tested the ability of single-wire electrodes to discriminate activity from multiple neurons under conditions of varying noise and neuronal cell density. Using extracellular single-unit recording, coupled with iontophoresis to drive cell activity across a wide dynamic range, we studied spike waveform variability, and explored systematic differences in single-unit spike waveform within and between brain regions as well as the influence of signal-to-noise ratio (SNR) on the similarity of spike waveforms. We also modelled spike misclassification for a range of cell densities based on neuronal recordings obtained at different SNRs. Modelling predictions were confirmed by classifying spike waveforms from multiple cells with various SNRs using a leading commercial spike-sorting system. Our results show that for single-wire recordings, multiple units can only be reliably distinguished under conditions of high recording SNR (≥4) and low neuronal density (≈20,000/ mm3). Physiological and behavioural changes, as well as technical limitations typical of awake animal preparations, reduce the accuracy of single-channel spike classification, resulting in serious classification errors. For SNR <4, the probability of misclassifying spikes approaches 100% in many cases. Our results suggest that in studies where the SNR is low or neuronal density is high, separation of distinct units needs to be evaluated with great caution

Imagined gait modulates neuronal network dynamics in the human pedunculopontine nucleus

The pedunculopontine nucleus (PPN) is a part of the mesencephalic locomotor region and is thought to be important for the initiation and maintenance of gait. Lesions of the PPN induce gait deficits, and the PPN has therefore emerged as a target for deep brain stimulation for the control of gait and postural disability. However, the role of the PPN in gait control is not understood. Using extracellular single-unit recordings in awake patients, we found that neurons in the PPN discharged as synchronous functional networks whose activity was phase locked to alpha oscillations. Neurons in the PPN responded to limb movement and imagined gait by dynamically changing network activity and decreasing alpha phase locking. Our results indicate that different synchronous networks are activated during initial motor planning and actual motion, and suggest that changes in gait initiation in Parkinson's disease may result from disrupted network activity in the PPN

ETUDE PAR MICRODIALYSE DES VARIATIONS DE GLUTAMATE ET DE GABA DANS LA SUBSTANCE NOIRE ET LE GLOBUS PALLIDUS INDUITES PAR LA STIMULATION ELECTRIQUE DU NOYAU SUBTHALAMIQUE CHEZ LE RAT (DOCTORAT NEUROSCIENCES)

GRENOBLE1-BU Médecine pharm. (385162101) / SudocPARIS-BIUM (751062103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Organic optoelectronic diodes as tactile sensors for soft-touch applications

The distributed sense of touch forms an essential component that defines real-time perception and situational awareness in humans. Electronic skins are an emerging technology in conferring an artificial sense of touch for smart human-machine interfaces. However, assigning a conformably distributed sense of touch over a large area has been challenging to replicate in modern medical, social, and industrial robots. Herein, we present a new class of soft tactile sensors that exploit the mechanisms of triplet-triplet annihilation, exciton harvesting, and a small Stokes shift in conjugated organic semiconductors such as rubrene. By multiplexing the electroluminescence and photosensing modes, we show that a compact optoelectronic array of multifunctional rubrene/fullerene diodes can accurately measure pressure, position, and surface deformation applied to an overlying elastomeric layer. The dynamic range of sensing is defined by mechanical properties of the elastomer. Such optoelectronic approach paves the way for soft, conformal, and large-area compatible electronic skins for medicine and robotics.</p

Light detection in open-circuit voltage mode of organic photodetectors

Organic photodetectors (OPDs) are promising candidates for next-generation light sensors as they combine unique material properties with high-level performance in converting photons into electrical signals. However, low-level light detection with OPD is often limited by device dark current. Here, the open-circuit voltage (Voc) regime of OPDs is shown to be efficient for detecting low light signals (−2). It is established that the light-dependence of Voc exhibits two distinct regimes as function of irradiance: linear and logarithmic. Whereas the observed logarithmic regime is well understood in organic photovoltaic cells (OPVs), it is shown experimentally and theoretically that the linear regime is due to the non-infinite shunt resistance of the OPD device. Overall, OPDs composed of rubrene and fullerene show photovoltage light sensitivity across nine orders of magnitude with a detection limit as low as 400 pW cm−2. A photovoltage responsivity of 1.75 V m2 W−1 demonstrates highly efficient performance without the necessity to supress high dark current. This approach opens up new possibilities for resolving low light signals and provides simplified design rules for OPDs.</p