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Developing manufacturing methods that are scalable and compatible with a roll-to-roll process with low waste of material has become a pressing need to transfer organic photovoltaics (OPVs) to a viable renewable energy source. For this purpose, various spray printing methods have been proposed. Among them, electrospray (ES) is an attractive option due to its negligible material waste, tunable droplet size, and tolerance to the substrate defects and roughness. Conventional ES with a circular spray footprint often makes the droplets well separated and unlikely to merge, giving rise to "coffee rings" which cause a rough and flawed film morphology. Here, a quadrupole electrode is introduced to generate a compressing electric field that squeezes the conical ES profile into the shape of a thin sheet. The numerical simulation and experimental data of the trajectories of sprayed droplets show that the quadrupole apparatus can effectively increase the long axis to short axis ratio of the oval spray footprint and hence bring droplets closer to each other and make the merging more likely for the deposited droplets. By promoting the merging of droplets, individual coffee rings are also suppressed. Thus, the quadrupole ES offers untapped opportunities for effectively reducing voids and improving the flatness of the ES-printed active layer. The devices with a PM6:N3 active layer printed by the sheet ES exhibited the highest power conversion efficiency (PCE) of up to 15.98%, which is a noticeable improvement over that (14.85%) of counterparts fabricated by a conventional conical ES. This is the highest PCE reported for ES-printed OPVs and is one of the most efficient spray-deposited OPVs so far. In addition, the all-spray-printed devices reached a PCE of 14.55%, which is also among the most efficient all-spray-printed OPVs.
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Many patients of advanced Parkinson's disease (PD) suffer from intractable axial symptoms (severe gait and postural impairments), which were recently speculated to be more relevant to cholinergic degeneration in the brainstem than dopaminergic degeneration in the substantia nigra compacta (SNc). To investigate the role of the cholinergic cells of the pedunculopontine tegmental nucleus (PPTg) on motor deficits, especially the axial motor impairments, we measured and analyzed the gait performance of sham lesion rats, SNc dopaminergic lesion rats, PPTg cholinergic lesion rats, and combined lesion rats by using the CatWalk system. Motor performance of PPTg cholinergic lesion rats was also tested on the rotarod. Independent loss of cholinergic neurons in the PPTg did not induce gait disturbance in CatWalk, but PPTg lesion rats showed motor impairments on the rotarod when the demands of the motor task increased. Both SNc lesion rats and combined lesion rats displayed significant changes in many gait parameters, but the terminal dual stance increased much higher in combined lesion group than SNc lesion group. Furthermore, combined lesion rats showed more severe freezing of gait (FOG) than SNc lesion rats during behavioral re-evaluations after lesion. These results suggest that the PPTg cholinergic neurons play a vital role in the occurrence of FOG in PD.
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Acetilcolina/metabolismo , Neuronas Colinérgicas/efectos de los fármacos , Marcha/efectos de los fármacos , Enfermedad de Parkinson/metabolismo , Núcleo Tegmental Pedunculopontino/efectos de los fármacos , Núcleo Tegmental Pedunculopontino/metabolismo , Animales , Colina O-Acetiltransferasa/inmunología , Dopamina/metabolismo , Inmunotoxinas/inmunología , Inmunotoxinas/farmacología , Masculino , Trastornos Motores/inducido químicamente , Trastornos Motores/complicaciones , Oxidopamina/farmacología , Enfermedad de Parkinson/complicaciones , Porción Compacta de la Sustancia Negra/efectos de los fármacos , Porción Compacta de la Sustancia Negra/metabolismo , Ratas , Prueba de Desempeño de Rotación con Aceleración ConstanteRESUMEN
The present study attempts to cultivate Porphyridium purpureum under different scale-up conditions for further development and commercialization of microalgae-derived PUFAs such as ARA and EPA. Different temperatures (25, 30, and 35 °C) and light intensities (70, 165, and 280 µmol/m2s) were applied to the 50 L pilot-scale cultivation of P. purpureum in ASW. The cultivation under the light intensity of 280 µmol/m2s at 35 °C obtained biomass concentration up to 9.52 g/L, total fatty acid content to 56.82 mg/g, and ARA content to 22.29 mg/g. While the maximum EPA content of 7.00 mg/g was achieved under the light intensity of 280 µmol/m2s at 25 °C and the highest ratio of UFAs to TFAs of 74.66% was also obtained in this trial. Both biomass concentration and TFAs content were improved by increasing light intensity and temperature. Moreover, the ratio of ARA to EPA was enhanced by increasing cultivation temperature under the light intensity of 280 µmol/m2s. In contrast with flask culture, the conversion of linoleic acid (C18:2) to ARA was enhanced in scale-up culture, leading to more ARA content. Phosphate limitation enhanced the synthesis of lipid and LPUFAs. Moreover, the biomass concentration and biosynthesis of palmitic acid were preferred by sufficient C (NaHCO3).
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Ácido Araquidónico/metabolismo , Microalgas/metabolismo , Porphyridium/metabolismo , Biomasa , Luz , Microalgas/crecimiento & desarrollo , Fosfatos/metabolismo , Porphyridium/crecimiento & desarrollo , TemperaturaRESUMEN
BACKGROUND: The microalga Porphyridium purpureum within Rhodophyta abundantly produces several valuable proteins, polysaccharides, pigments and long-chain polyunsaturated fatty acid; it is especially effective in accumulating arachidonic acid (ARA). However, this high ARA yield is always achieved in conditions unfavourable for cell growth. In this study, we present a method for obtaining desirable ARA levels from P. purpureum while simultaneously promoting cell growth using appropriate concentrations of the growth hormone 5-Aminolevulinic acid (5-ALA). RESULTS: Both the biomass and the ARA content of P. purpureum were enhanced by stimulation with 20 mg/L 5-ALA, leading to an optimal ARA yield of 170.32 mg/L-a 70.82% increase compared with control conditions. This ARA yield is the highest ever reported for microalgae. Based on variations in the fatty acid composition, total lipids, total proteins, total carbohydrates and pigment content during the cultivation period, we propose that the accumulation of ARA stimulated by 5-ALA occurs at the expense of other UFAs and total proteins, which may be related to decreased zeaxanthin. Lipidomic analysis revealed that triacylglycerols (TAGs) accounted for 47.5 ± 3.6% of all detected lipids, followed by phosphatidylglycerol (PG) and digalactosyldiacylglycerol (DGDG). As the levels of the most abundant TAGs increased under 5-ALA promotion and because 78.1 ± 3.4% (by weight) of detected TAG-branched chains contained ARA, the increase of ARA was mainly caused by TAG accumulation. CONCLUSIONS: This work demonstrated a simple and effective strategy to promote both biomass and ARA yield in P. purpureum by introducing a small amount of 5-ALA. These results are helpful for understanding the microalgae metabolic pathways affected by phytohormones and for guiding the development of bioproducts from microalgae.
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Oscillatory activity has been well-studied in many structures within cortico-basal ganglia circuits, but it is not well understood within the pedunculopontine nucleus (PPN), which was recently introduced as a potential target for the treatment of gait and postural impairments in advanced stages of Parkinson's disease (PD). To investigate oscillatory activity in the PPN and its relationship with oscillatory activity in cortico-basal ganglia circuits, we simultaneously recorded local field potentials in the PPN, primary motor cortex (M1), and subthalamic nucleus (STN) of 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian rats during resting and walking. After analysis of power spectral density, coherence, and partial Granger causality, three major findings emerged: 1) after 6-OHDA lesions, beta band oscillations were enhanced in all three regions during walking; 2) the direction of information flow for beta oscillations among the three structures was STNâM1, STNâPPN, and PPNâM1; 3) after the treatment of levodopa, beta activity in the three regions was reduced significantly and the flow of beta band was also abrogated. Our results suggest that beta activity in the PPN is transmitted from the basal ganglia and probably comes from the STN, and the STN plays a dominant role in the network of causal interactions for beta activity. Thus, the STN may be a potential source of aberrant beta band oscillations in PD. Levodopa can inhibit beta activity in the PPN of parkinsonian rats but cannot relieve parkinsonian patients' axial symptoms clinically. Therefore, beta oscillations may not be the major cause of axial symptoms.
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Ritmo beta/fisiología , Corteza Motora/fisiopatología , Enfermedad de Parkinson/patología , Núcleo Tegmental Pedunculopontino/fisiopatología , Núcleo Subtalámico/fisiopatología , Caminata/fisiología , Animales , Antiparkinsonianos/farmacología , Antiparkinsonianos/uso terapéutico , Modelos Animales de Enfermedad , Levodopa/farmacología , Levodopa/uso terapéutico , Masculino , Oxidopamina/toxicidad , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson/fisiopatología , Ratas , Ratas Sprague-Dawley , Análisis Espectral , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Microalgal biomass as renewable energy source is believed to be of great potential for reliable and sustainable biofuels production. However, microalgal biomass production is pinned by harvesting and dewatering stage thus hindering the developing and growing microalgae biotechnology industries. Flotation technology applied in mineral industry could be potentially applied in microalgae harvesting and dewatering, however substantial knowledge on different flotation units is essential. This paper presents an overview on different flotation units as promising cost-effective technologies for microalgae harvesting thus bestowing for further research in development and commercialization of microalgae based biofuels. Dispersed air flotation was found to be less energy consuming. Moreover, Jameson cell flotation and dispersed ozone flotation are believed to be energy efficient microalgae flotation approaches. Microalgae harvesting and dewatering by flotation is still at embryonic stage, therefore extended studies with the focus on life cycle assessment, sustainability of the flotation unit, optimization of the operating parameters using different algal species is imperative. Though there are a number of challenges in microalgae harvesting and dewatering, with well designed and developed cultivation, harvesting/dewatering, extraction and conversion technologies, progressively, microalgae technology will be of great potential for biological carbon sequestration, biofuels and biochemicals production.
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Biocombustibles , Biotecnología/métodos , Microalgas/crecimiento & desarrollo , Biomasa , Cinética , Energía RenovableRESUMEN
Polyunsaturated fatty acids (PUFAs) are highly appreciated on their nutritive value for human health and aquaculture. P. purpureum, one of the red microalgae acknowledged as a promising accumulator of ARA, was chosen as the target algae in the present research. Effects of sodium bicarbonate (0.04-1.2 g/L), temperature (25, 30 and 33 °C) and phosphate (0.00-0.14 g/L) on biomass yield, total fatty acids (TFA) and arachidonic acid (ARA) accumulation were investigated systemically. NaHCO3 dose of 0.8 g/L and moderate temperature of 30 °C were preferred. In addition, TFA and ARA production were significantly enhanced by an appropriate concentration of phosphate, and the highest TFA yield of 666.38 mg/L and ARA yield of 159.74 mg/L were obtained at a phosphate concentration of 0.035 g/L. Interestingly, with phosphate concentration continuing to fall, UFA/TFA and ARA/EPA ratios were increased accordingly, suggesting that phosphate limitation promoted unsaturated fatty acids and arachidonic acid biosynthesis. Low concentration of phosphate may be favored to increase the enzymatic activities of ∆6-desaturase, which played a key role in catalyzing the conversion of C16:0 to C18:2, and thus the selectivity of UFA increased. Meanwhile, the increase of ARA selectivity could be attributed to ω6 pathway promotion and ∆17-desaturase activity inhibition with phosphate limitation. Phosphate limitation strategy enhanced unsaturated fatty acids and ARA biosynthesis in P. purpureum, and can be applied in commercial scale manufacturing and commercialization of ARA.
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Ácido Araquidónico/biosíntesis , Ácidos Grasos Insaturados/metabolismo , Fosfatos/metabolismo , Porphyridium/metabolismo , Biomasa , TemperaturaRESUMEN
The pedunculopontine nucleus (PPN) is connected to spinal, cerebellar and cerebral motor control structures and can be activated with external electrodes. Intrinsic cholinergic neuronal degeneration in the PPN is associated with postural instabilities and gait disturbances (PIGD) in advanced Parkinson's disease (PD). Clinical studies have demonstrated that PPN stimulation may improve PIGD. We investigated this claim and the underlying mechanisms using the 6-hydroxydopamine (6-OHDA) hemilesion model of PD. In this study, gait-related parameters, including the base of support (BOS), stride length, and maximum contact area, were analyzed via CatWalk gait analysis following PPN-low frequency stimulation (LFS) of rats with unilateral 6-OHDA lesions. Additionally, neurotransmitter concentrations in the ventrolateral thalamic nucleus (VL) were measured by microdialysis and liquid chromatography-mass spectrometry (LC-MS). Our data revealed that unilateral 6-OHDA lesions of the medial forebrain bundle (MFB) induced significant gait deficits. PPN-LFS significantly improved the BOS (hindlimb) and maximum contact area (impaired forelimb) scores, whereas no other gait parameters were significantly affected. Unilateral 6-OHDA MFB lesions significantly decreased acetylcholine (ACh) and moderately decreased noradrenaline (NA) concentrations in the VL. PPN-LFS mildly reversed the ACh loss in the VL in the lesioned rats but did not alter the NA levels. Taken together, our data indicate that PPN-LFS is useful for treating gait deficits of PD and that these effects are probably mediated by a rebalancing of ACh levels in the PPN-VL pathway. Thus, our findings provide possible insight into the mechanisms underlying PIGD in PD.
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Marcha , Neurotransmisores/metabolismo , Oxidopamina , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/fisiopatología , Núcleo Tegmental Pedunculopontino/fisiopatología , Núcleos Talámicos Ventrales/metabolismo , Núcleos Talámicos Ventrales/fisiopatología , Acetilcolina/metabolismo , Animales , Estimulación Eléctrica , Masculino , Norepinefrina/metabolismo , Enfermedad de Parkinson/etiología , Ratas Sprague-DawleyRESUMEN
In this study, different light intensities (80, 160, 240 and 320 µmol/m(2) s) and various mediums including control medium (CM), N/P rich medium (NPM), N rich medium (NM), and P rich medium (PM) were applied for cultivation of Chlorella sp. It was revealed that cultivation of Chlorella sp. in CM under the light intensity of 320 µmol/m(2) s led to a lipid content up to 30% enhancement, which was higher than the results of other cases. A rather high unsaturated fatty acid (UFA) content of 7.5% and unsaturated fatty acid/total fatty acid (UFA/TFA) ratio of 0.73 were obtained under 320 µmol/m(2) s in CM, indicating that the CM-320 system was applicable for the generation of UFA. Moreover, Chlorella sp. cultivated in PM under 320 µmol/m(2) s provided higher TFA content (7.3%), which was appropriate for biofuel production.
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Chlorella/metabolismo , Ácidos Grasos Insaturados/metabolismo , Luz , Metabolismo de los Lípidos , Nitrógeno/metabolismo , Fósforo/metabolismo , Chlorella/crecimiento & desarrolloRESUMEN
OBJECTIVE: The aim of this study was to investigate voluntary wheel running behavior in the unilateral 6-hydroxydopamine (6-OHDA) rat model. METHODS: Male Sprague-Dawley rats were assigned to 2 groups : 6-OHDA group (n=17) and control group (n=8). The unilateral 6-OHDA rat model was induced by injection of 6-OHDA into unilateral medial forebrain bundle using a stereotaxic instrument. Voluntary wheel running activity was assessed per day in successfully lesioned rats (n=10) and control rats. Each behavioral test lasted an hour. The following parameters were investigated during behavioral tests : the number of running bouts, the distance moved in the wheel, average peak speed in running bouts and average duration from the running start to the peak speed. RESULTS: The number of running bouts and the distance moved in the wheel were significantly decreased in successfully lesioned rats compared with control rats. In addition, average peak speed in running bouts was decreased, and average duration from the running start to the peak speed was increased in lesioned animals, which might indicate motor deficits in these rats. These behavioral changes were still observed 42 days after lesion. CONCLUSION: Voluntary wheel running behavior is impaired in the unilateral 6-OHDA rat model and may represent a useful tool to quantify motor deficits in this model.
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Gait deficits are important clinical symptoms of Parkinson's disease (PD) but are rarely studied. In this study we made three different rat PD models by administration of 6-hydroxydopamine into caudate putamen (CPU), medial forebrain bundle (MFB) and substantia nigra compact (SNC). We evaluated the gait changes in these models by using a computer-assisted CatWalk system. Correlations of gait parameters with tyrosine hydroxylase protein levels in the CPU and SNC were also investigated. The gait readouts were significantly impaired in both the MFB and SNC groups. However, the MFB group showed a more pronounced impairment than the SNC group. In contrast, only mild and incomplete gait impairment occurred in the CPU group. In addition, some gait parameters demonstrated close correlation with the protein levels of TH. This paper suggests that the 6-hydroxydopamine-induced MFB model is more propitious to study gait dysfunction than the other two models and the CatWalk system can provide reliable and objective criteria to stratify gait changes arising from 6-hydroxydopamine lesioned rats. These findings may hold promise in the study of PD disease progression and new therapeutic methods.
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Marcha , Enfermedad de Parkinson/fisiopatología , Animales , Recuento de Células , Masculino , Neuronas/patología , Oxidopamina , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Putamen/metabolismo , Ratas Sprague-Dawley , Sustancia Negra/metabolismo , Sustancia Negra/patología , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
BACKGROUND: The ability to encode noxious stimulus intensity is essential for the neural processing of pain perception. It is well accepted that the intensity information is transmitted within both sensory and affective pathways. However, it remains unclear what the encoding patterns are in the thalamocortical brain regions, and whether the dual pain systems share similar responsibility in intensity coding. RESULTS: Multichannel single-unit recordings were used to investigate the activity of individual neurons and neuronal ensembles in the rat brain following the application of noxious laser stimuli of increasing intensity to the hindpaw. Four brain regions were monitored, including two within the lateral sensory pain pathway, namely, the ventral posterior lateral thalamic nuclei and the primary somatosensory cortex, and two in the medial pathway, namely, the medial dorsal thalamic nuclei and the anterior cingulate cortex. Neuron number, firing rate, and ensemble spike count codings were examined in this study. Our results showed that the noxious laser stimulation evoked double-peak responses in all recorded brain regions. Significant correlations were found between the laser intensity and the number of responsive neurons, the firing rates, as well as the mass spike counts (MSCs). MSC coding was generally more efficient than the other two methods. Moreover, the coding capacities of neurons in the two pathways were comparable. CONCLUSION: This study demonstrated the collective contribution of medial and lateral pathway neurons to the noxious intensity coding. Additionally, we provide evidence that ensemble spike count may be the most reliable method for coding pain intensity in the brain.
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Potenciales de Acción/fisiología , Nocicepción/fisiología , Nociceptores/metabolismo , Dolor/fisiopatología , Animales , Conducta Animal , Recuento de Células , Electrodos , Giro del Cíngulo/patología , Giro del Cíngulo/fisiopatología , Rayos Láser , Núcleo Talámico Mediodorsal/patología , Núcleo Talámico Mediodorsal/fisiopatología , Vías Nerviosas , Nociceptores/patología , Dolor/patología , Estimulación Física , Ratas , Corteza Somatosensorial/patología , Corteza Somatosensorial/fisiopatología , Núcleos Talámicos Ventrales/patología , Núcleos Talámicos Ventrales/fisiopatologíaRESUMEN
The question pursued in this study was when neural activity appears in the cortico-basal ganglia system that could predict alternate behavioral responses in a reaction time (RT) task. In this protocol, rats first performed a nose poke to initiate a trial, depressed a lever when presented, and then released the lever after a tone cue. Multiple-channel, single-unit recordings (up to 62 units) were obtained simultaneously from the prefrontal cortex, the dorsal medial striatum, the globus pallidus, and the substantia nigra pars reticulata in a single rat during a session. Results indicated that (1) global alterations of neural activity appeared in clusters, which was associated with different behavioral components and observed in each of the targeted areas; (2) small independent subsets of neurons responded differently between error (lever was released before tone presentation) and correct trials (lever was released within 0.5s after tone onset) during these behavioral episodes; (3) significant correlations between RTs and single units activities were found in the early preparation phases of the task. The results reveal that complex early preparatory activity exists several seconds before the final movements in a RT task, which may determine executive functions leading to rapid decoding of alternate behavioral performances.
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Ganglios Basales/fisiología , Lóbulo Frontal/fisiología , Neuronas/fisiología , Desempeño Psicomotor/fisiología , Tiempo de Reacción/fisiología , Animales , Condicionamiento Operante/fisiología , Masculino , Valor Predictivo de las Pruebas , Ratas , Ratas Sprague-DawleyRESUMEN
Deep brain stimulation (DBS) has been used in the clinic to treat Parkinson's disease (PD) and other neuropsychiatric disorders. Our previous work has shown that DBS in the subthalamic nucleus (STN) can improve major motor deficits, and induce a variety of neural responses in rats with unilateral dopamine (DA) lesions. In the present study, we examined the effect of STN DBS on reaction time (RT) performance and parallel changes in neural activity in the cortico-basal ganglia regions of partially bilateral DA- lesioned rats. We recorded neural activity with a multiple-channel single-unit electrode system in the primary motor cortex (MI), the STN, and the substantia nigra pars reticulata (SNr) during RT test. RT performance was severely impaired following bilateral injection of 6-OHDA into the dorsolateral part of the striatum. In parallel with such behavioral impairments, the number of responsive neurons to different behavioral events was remarkably decreased after DA lesion. Bilateral STN DBS improved RT performance in 6-OHDA lesioned rats, and restored operational behavior-related neural responses in cortico-basal ganglia regions. These behavioral and electrophysiological effects of DBS lasted nearly an hour after DBS termination. These results demonstrate that a partial DA lesion-induced impairment of RT performance is associated with changes in neural activity in the cortico-basal ganglia circuit. Furthermore, STN DBS can reverse changes in behavior and neural activity caused by partial DA depletion. The observed long-lasting beneficial effect of STN DBS suggests the involvement of the mechanism of neural plasticity in modulating cortico-basal ganglia circuits.
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Trastornos del Conocimiento/terapia , Estimulación Encefálica Profunda/métodos , Trastornos del Movimiento/terapia , Enfermedad de Parkinson/terapia , Núcleo Subtalámico/fisiología , Animales , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/fisiopatología , Estimulación Encefálica Profunda/instrumentación , Modelos Animales de Enfermedad , Terapia por Estimulación Eléctrica/métodos , Electrodos Implantados , Electrofisiología/métodos , Masculino , Corteza Motora/fisiopatología , Trastornos del Movimiento/etiología , Trastornos del Movimiento/fisiopatología , Vías Nerviosas/patología , Vías Nerviosas/fisiopatología , Plasticidad Neuronal/fisiología , Oxidopamina/toxicidad , Enfermedad de Parkinson/fisiopatología , Ratas , Ratas Sprague-Dawley , Recuperación de la Función/fisiología , Sustancia Negra/fisiopatología , Núcleo Subtalámico/cirugía , Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Despite the wide-spread use of morphine and related opioid agonists in clinic and their powerful analgesic effects, our understanding of the neural mechanisms underlying opioid analgesia at supraspinal levels is quite limited. The present study was designed to investigate the modulative effect of morphine on nociceptive processing in the medial and lateral pain pathways using a multiple single-unit recording technique. Pain evoked neuronal activities were simultaneously recorded from the primary somatosensory cortex (SI), ventral posterolateral thalamus (VPL), anterior cingulate cortex (ACC), and medial dorsal thalamus (MD) with eight-wire microelectrode arrays in awake rats. RESULTS: The results showed that the noxious heat evoked responses of single neurons in all of the four areas were depressed after systemic injection of 5 mg/kg morphine. The depressive effects of morphine included (i) decreasing the neuronal response magnitude; (ii) reducing the fraction of responding neurons, and (iii) shortening the response duration. In addition, the capability of cortical and thalamic neural ensembles to discriminate noxious from innocuous stimuli was decreased by morphine within both pain pathways. Meanwhile, morphine suppressed the pain-evoked changes in the information flow from medial to lateral pathway and from cortex to thalamus. These effects were completely blocked by pre-treatment with the opiate receptor antagonist naloxone. CONCLUSION: These results suggest that morphine exerts analgesic effects through suppressing both sensory and affective dimensions of pain.
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Morfina/farmacología , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiopatología , Dolor/fisiopatología , Animales , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/fisiopatología , Masculino , Neuronas/efectos de los fármacos , Neuronas/fisiología , Estimulación Física , Ratas , Ratas Sprague-Dawley , Temperatura , Factores de TiempoRESUMEN
BACKGROUND: Expectation is a very potent pain modulator in both humans and animals. There is evidence that pain transmission neurons are modulated by expectation preceding painful stimuli. Nonetheless, few studies have examined the influence of pain expectation on the pain-related neuronal activity and the functional connectivity within the central nociceptive network. RESULTS: This study used a tone-laser conditioning paradigm to establish the pain expectation in rats, and simultaneously recorded the anterior cingulate cortex (ACC), the medial dorsal thalamus (MD), and the primary somatosensory cortex (SI) to investigate the effect of pain expectation on laser-induced neuronal responses. Cross-correlation and partial directed coherence analysis were used to determine the functional interactions within and between the recorded areas during nociceptive transmission. The results showed that under anticipation condition, the neuronal activity to the auditory cue was significantly increased in the ACC area, whereas those to actual noxious stimuli were enhanced in all the recorded areas. Furthermore, neuronal correlations within and between these areas were significantly increased under conditions of expectation compared to those under non-expectation conditions, indicating an enhanced synchronization of neural activity within the pain network. In addition, information flow from the medial (ACC and MD) to the lateral (SI cortex) pain pathway increased, suggesting that the emotion-related neural circuits may modulate the neuronal activity in the somatosensory pathway during nociceptive transmission. CONCLUSION: These results demonstrate that the nociceptive processing in both medial and lateral pain systems is modulated by the expectation of pain.
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Nociceptores/fisiología , Dolor/metabolismo , Dolor/psicología , Transmisión Sináptica/fisiología , Animales , Masculino , Dimensión del Dolor , Ratas , Ratas Sprague-Dawley , Corteza Somatosensorial/fisiología , Tálamo/fisiologíaRESUMEN
Considerable evidence supports that pain is encoded in a large, widespread network that consists of the thalamus, cortex, as well as limbic system. However, the temporal properties of the neural matrix in pain processing were largely unknown. In the present study, we simultaneously recorded thalamic and cortical neuronal discharges elicited by brief noxious or innocuous electrical stimulus in awake rats. The discrimination performance of the neural ensembles in differentiating noxious from innocuous inputs was calculated using different window sizes at the millisecond and second level, respectively. The results demonstrated that coding information emerged in a quantum-like manner; the minimum spike-train length for discriminating noxious from innocuous inputs was 40 ms. The nociceptive coding activity was temporally dynamic, and could be preserved for a relatively long time (3-4 s) within the thalamocortical loops, independent of the initial brief stimuli. These results suggest that the nociceptive signals may be reverberatory within the thalamocortical loops, hence keeping the neurosignature for central pain representation.
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Mapeo Encefálico , Corteza Cerebral/fisiología , Discriminación en Psicología/fisiología , Dolor/fisiopatología , Tálamo/fisiología , Animales , Conducta Animal/fisiología , Depresión de Propagación Cortical , Relación Dosis-Respuesta en la Radiación , Estimulación Eléctrica/efectos adversos , Masculino , Análisis Numérico Asistido por Computador , Dolor/etiología , Dolor/patología , Dimensión del Dolor , Ratas , Ratas Sprague-Dawley , Análisis Espectral , Factores de TiempoRESUMEN
Several rodent models of deep brain stimulation (DBS) have been developed in recent years. Electrophysiological and neurochemical studies have been performed to examine the mechanisms underlying the effects of DBS. In vitro studies have provided deep insights into the role of ion channels in response to brain stimulation. In vivo studies reveal neural responses in the context of intact neural circuits. Most importantly, recording of neural responses to behaviorally effective DBS in freely moving animals provides a direct means for examining how DBS modulates the basal ganglia thalamocortical circuits and thereby improves motor function. DBS can modulate firing rate, normalize irregular burst firing patterns and reduce low frequency oscillations associated with the Parkinsonian state. Our current efforts are focused on elucidating the mechanisms by which DBS effects on neural circuitry improve motor performance. New behavioral models and improved recording techniques will aide researchers conducting future DBS studies in a variety of behavioral modalities and enable new treatment strategies to be explored, such as closed-loop stimulations based on real time computation of ensemble neural activity.
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Ganglios Basales/fisiopatología , Estimulación Encefálica Profunda/métodos , Modelos Animales de Enfermedad , Enfermedad de Parkinson/terapia , Núcleo Subtalámico/fisiopatología , Animales , Ratones , Enfermedad de Parkinson/fisiopatología , RatasRESUMEN
Several rodent models of deep brain stimulation (DBS) have been developed in recent years. Electrophysiological and neurochemical studies have been performed to examine the mechanisms underlying the effects of DBS. In vitro studies have provided deep insights into the role of ion channels in response to brain stimulation. In vivo studies reveal neural responses in the context of intact neural circuits. Most importantly, recording of neural responses to behaviorally effective DBS in freely moving animals provides a direct means for examining how DBS modulates the basal ganglia thalamocortical circuits and thereby improves motor function. DBS can modulate firing rate, normalize irregular burst firing patterns and reduce low-frequency oscillations associated with the Parkinsonian state. Our current efforts are focused on elucidating the mechanisms by which DBS effects on neural circuitry improve motor performance. New behavioral models and improved recording techniques will aide researchers conducting future DBS studies in a variety of behavioral modalities and enable new treatment strategies to be explored, such as closed-loop stimulations based on real-time computation of ensemble neural activity.
Asunto(s)
Estimulación Encefálica Profunda/métodos , Modelos Animales de Enfermedad , Terapia por Estimulación Eléctrica , Neuronas/fisiología , Enfermedad de Parkinson/cirugía , Animales , Humanos , Neuronas/efectos de la radiación , Enfermedad de Parkinson/patología , RoedoresRESUMEN
Pain is a multidimensional phenomenon and processed in a neural network. The supraspinal, brain mechanisms are increasingly recognized in playing a major role in the representation and modulation of pain. The aim of the current study is to investigate the functional interactions between cortex and thalamus during nociceptive processing, by observing the pain-related information flow and neuronal correlations within thalamo-cortical pathways. Pain-evoked, single-neuron activity was recorded in awake Sprague-Dawley rats with a Magnet system. Eight-wire microarrays were implanted into four different brain regions, i.e., the primary somatosensory (SI) and anterior cingulate cortex (ACC), as well as ventral posterior (VP) and medial dorsal thalamus (MD). Noxious radiant heat was delivered to the rat hind paws on the side contralateral to the recording regions. A large number of responsive neurons were recorded in the four brain areas. Directed coherence analysis revealed that the amount of information flow was significantly increased from SI cortex to VP thalamus following noxious stimuli, suggesting that SI cortex has descending influence on thalamic neurons during pain processing. Moreover, more correlated neuronal activities indicated by crosscorrelation histograms were found between cortical and thalamic neurons, with cortical neurons firing ahead of thalamic units. On basis of the above findings, we propose that nociceptive responses are modulated by corticothalamic feedback during nociceptive transmission, which may be tight in the lateral pathway, while loose in the medial pathway.