RESUMO
This article presents an experimental demonstration of a spectroscopic method based on the dispersion of the scattering spectrum from laser-illuminated liquid water collected through a rubidium atomic vapor prism cell. Resonant absorption at 780 nm suppresses Mie/Rayleigh scattering and the steep gradients in refractive index near the 780 nm absorption lines separate Brillouin scattering from Raman scattering in liquid water. The opposing spatial displacements of the Stokes and Anti-Stokes shifted Brillouin peaks yield a measurement of their spectral shifts and thus the temperature or salinity of the water. Performance of the prism cell was mapped with a frequency tunable laser for frequency offsets from the center of the rubidium absorption feature of between -15 GHz and 15 GHz and at rubidium cell temperatures between 148 °C and 177 °C. The experimental results are compared with a numerical model and show good agreement with the scattering peak displacements within experimental uncertainties of probe frequency and cell temperature. In the present configuration, the minimum detectable frequency shift is estimated to be 15.5 MHz. Experiments were conducted in water demonstrating the utility of this method for the measurement of water temperature. Liquid water LiDAR was suggested as one of the possible applications for this method and several ways to improve the experimental setup and cell temperature stability were identified.
RESUMO
This work reports the measurement of two-dimensional electron properties over a nanosecond scale integration time across a femtosecond laser-induced plasma filament in atmospheric pressure argon. Radial electron properties across the [Formula: see text] [Formula: see text]m diameter filament are obtained at discrete axial locations at 2.5 mm steps by one-dimensional high-resolution laser Thomson scattering with a spatial resolution of 10 [Formula: see text]m. These measurements reveal plasma structural information in the filament. The Thomson spectral lineshapes exhibit clear spectral sidebands with an [Formula: see text] parameter [Formula: see text], enabling the measurement of both electron temperature and density profiles. These measurements yield electron densities on the order of [Formula: see text]/m[Formula: see text] and electron temperatures of [Formula: see text] eV. Heating from the probe laser due to inverse bremsstrahlung is taken into account to correct the Thomson scattering electron temperature measurements. Under these conditions, electron-neutral collision induced bremsstrahlung becomes the dominant laser-induced plasma heating process associated with the probe laser. The measurements reveal structural features of the filament, including an asymmetrically skewed density structure in the axial direction and reversed radial distributions of electron density and temperature.
RESUMO
This Letter describes, to the best of our knowledge, a new approach to flow tagging, nitric oxide (NO) Ionization Induced Flow Tagging and Imaging (NiiFTI), and presents the first experimental demonstration for single-shot velocimetry in a near Mach 6 hypersonic flow at 250 kHz. The mean velocity of 860 m/s was measured with a single-shot standard deviation of as low as 3.4 m/s and mean velocity uncertainty of 5.5 m/s. NiiFTI is characterized by a long fluorescence lifetime of nitrogen with 1e decay of approximately 50 µs measured in air. The method relies on a single nanosecond laser combined with a high-speed camera, creating an opportunity for the utilization of a typical nitric oxide (NO) laser-induced fluorescence (LIF) experimental setup with minor modifications as well as pulse-burst lasers (PBLs) for ultrahigh repetition rates.
RESUMO
Suicide pacts among elderly couples afflicted by a terminal disease process present a significant challenge to emergency clinicians. If one member of the pair aborts their attempt, the surviving member of a dual suicide attempt can present a complex case with numerous clinical issues reflected by Hickam's dictum rather than by Occam's razor. Thus, emergency clinicians must keenly search for a multitude of concomitant but compounding conditions, potentially projected onto pre-existing comorbidities in an elderly population. The authors present a case of a suicide pact in which one member of the couple completed the attempt while the surviving member experienced carbon monoxide toxicity, compartment syndrome, rhabdomyolysis, and renal failure following her aborted suicide attempt.
RESUMO
This work presents the first, to the best of our knowledge, experimental demonstration of slow light imaging spectroscopy for thermometry of liquid water. This novel technique for measuring temperature relies on detecting the spectral shift of Brillouin peaks in water using the temporal delay through a cell containing an atomic vapor. Stand-off sensing capabilities are achieved by time-domain measurements of Brillouin scattering tuned to be near a rubidium atomic resonance and passed through a cell filled with rubidium vapor. An injection seeded optical parametric oscillator (OPO) is demonstrated to be a versatile light source for slow light imaging spectroscopy applications. The narrow OPO pulse spectrum allows for a precise profiling of slow light features of rubidium and accurate tracking of the temperature dependence of Brillouin scattering spectral shift. A comparison between the experimental data and numerical simulation over a temperature range of 20 to 99 degrees Celsius shows a good agreement for both qualitative and quantitative results.
RESUMO
Animal models of human brain disorders permit researchers to explore disease mechanisms and to test potential therapies. However, therapeutic molecules derived from animal models often translate poorly to the clinic. Although human data may be more relevant, experiments on patients are constrained, and living tissue is unavailable for many disorders. Here, we compare work on animal models and on human tissue for three epileptic syndromes where human tissue is excised therapeutically: (1) acquired temporal lobe epilepsies, (2) inherited epilepsies associated with cortical malformations, and (3) peritumoral epilepsies. Animal models rest on assumed equivalencies between human brains and brains of mice, the most frequently used model animal. We ask how differences between mouse and human brains could influence models. General principles and compromises in model construction and validation are examined for a range of neurological diseases. Models may be judged on how well they predict novel therapeutic molecules or new mechanisms. The efficacy and safety of new molecules are evaluated in clinical trials. We judge new mechanisms by comparing data from work on animal models with data from work on patient tissue. In conclusion, we stress the need to cross-verify findings from animal models and from living human tissue to avoid the assumption that mechanisms are identical.
Assuntos
Epilepsia do Lobo Temporal , Epilepsia , Síndromes Epilépticas , Humanos , Animais , Camundongos , Epilepsia/genética , Epilepsia/terapia , Encéfalo , Modelos AnimaisRESUMO
Ultrasound is an essential tool for guidance of many minimally-invasive surgical and interventional procedures, where accurate placement of the interventional device is critical to avoid adverse events. Needle insertion procedures for anaesthesia, fetal medicine and tumour biopsy are commonly ultrasound-guided, and misplacement of the needle may lead to complications such as nerve damage, organ injury or pregnancy loss. Clear visibility of the needle tip is therefore critical, but visibility is often precluded by tissue heterogeneities or specular reflections from the needle shaft. This paper presents the in vitro and ex vivo accuracy of a new, real-time, ultrasound needle tip tracking system for guidance of fetal interventions. A fibre-optic, Fabry-Pérot interferometer hydrophone is integrated into an intraoperative needle and used to localise the needle tip within a handheld ultrasound field. While previous, related work has been based on research ultrasound systems with bespoke transmission sequences, the new system-developed under the ISO 13485 Medical Devices quality standard-operates as an adjunct to a commercial ultrasound imaging system and therefore provides the image quality expected in the clinic, superimposing a cross-hair onto the ultrasound image at the needle tip position. Tracking accuracy was determined by translating the needle tip to 356 known positions in the ultrasound field of view in a tank of water, and by comparison to manual labelling of the the position of the needle in B-mode US images during an insertion into an ex vivo phantom. In water, the mean distance between tracked and true positions was 0.7 ± 0.4 mm with a mean repeatability of 0.3 ± 0.2 mm. In the tissue phantom, the mean distance between tracked and labelled positions was 1.1 ± 0.7 mm. Tracking performance was found to be independent of needle angle. The study demonstrates the performance and clinical compatibility of ultrasound needle tracking, an essential step towards a first-in-human study.
Assuntos
Tecnologia de Fibra Óptica , Agulhas , Gravidez , Feminino , Humanos , Ultrassonografia , Imagens de Fantasmas , Água , Ultrassonografia de Intervenção/métodosRESUMO
A number of commentators have recently called for a re-examination of the purpose and value of undergraduate education, arguing that change is required if universities are to deliver the value in educational outcomes that students and communities now require for a changing and challenging world (for example, Aoun, 2017; Bok, 2020; Davidson, 2017; Fischman & Gardner, 2022). Indeed, some have argued that such change is necessary to stem an emerging crisis in universities' 'social license to operate' (Bok, 2020). In this paper, we review the case for undergraduate curriculum change and present a case study of one Australian university's engagement with this challenge, describing the reasons for change, the desired outcomes, and some early impacts on students' study patterns. The change took place at the University of Sydney over the period from 2014 to 2021 with a new undergraduate curriculum introduced for commencing students from 2018. Intended to prepare students for a changing world, the new curriculum sought a balance between graduates' expertise in a primary field of study and a set of broader capabilities that would support their capacity for future learning and for creative and effective engagement in life and career, including an understanding of broader intellectual landscapes; the skills for collaboration, invention, and influence; and the integration of knowledge with professional and personal ethics and values. The aspiration to develop such capabilities is shared with many universities around the world, and we describe here how the available evidence base was used to guide whole-of-University curriculum redesign in this case. We also identify areas where further research would be of value.
RESUMO
Of the 13 known independent zoonoses of simian immunodeficiency viruses to humans, only one, leading to human immunodeficiency virus (HIV) type 1(M) has become pandemic, causing over 80 million human infections. To understand the specific features associated with pandemic human-to-human HIV spread, we compared replication of HIV-1(M) with non-pandemic HIV-(O) and HIV-2 strains in myeloid cell models. We found that non-pandemic HIV lineages replicate less well than HIV-1(M) owing to activation of cGAS and TRIM5-mediated antiviral responses. We applied phylogenetic and X-ray crystallography structural analyses to identify differences between pandemic and non-pandemic HIV capsids. We found that genetic reversal of two specific amino acid adaptations in HIV-1(M) enables activation of TRIM5, cGAS and innate immune responses. We propose a model in which the parental lineage of pandemic HIV-1(M) evolved a capsid that prevents cGAS and TRIM5 triggering, thereby allowing silent replication in myeloid cells. We hypothesize that this capsid adaptation promotes human-to-human spread through avoidance of innate immune response activation.
Assuntos
Infecções por HIV , HIV-1 , Vírus da Imunodeficiência Símia , Animais , Humanos , Filogenia , Vírus da Imunodeficiência Símia/metabolismo , Capsídeo/metabolismo , HIV-1/genética , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Infecções por HIV/epidemiologia , Infecções por HIV/metabolismo , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Fibromuscular dysplasia (FMD) is a non-atherosclerotic, non-inflammatory disorder of the arterial wall muscular layer which can lead to arterial stenosis, occlusion, and dissection. Clinical presentations of FMD vary depending on the arterial territories involved, often leading to diagnostic challenges. This case report describes an exceptionally unusual presentation of FMD, not previously described, affecting a previously fit and well 37-year-old female presenting with bilateral renal infarction, sequential vertebral artery dissections, mesenteric ischaemia, and the requirement for continued renal replacement. This report highlights how unusual presentations of FMD can mask the underlying diagnosis. Early consideration of FMD in a differential diagnosis can guide an effective management strategy, including appropriate imaging and multi-speciality involvement.
RESUMO
The type one interferon induced restriction factor Myxovirus resistance B (MxB) restricts HIV-1 nuclear entry evidenced by inhibition of 2-LTR but not linear forms of viral DNA. The HIV-1 capsid is the key determinant of MxB sensitivity and cofactor binding defective HIV-1 capsid mutants P90A (defective for cyclophilin A and Nup358 recruitment) and N74D (defective for CPSF6 recruitment) have reduced dependency on nuclear transport associated cofactors, altered integration targeting preferences and are not restricted by MxB expression. This has suggested that nuclear import mechanism may determine MxB sensitivity. Here we have use genetics to separate HIV-1 nuclear import cofactor dependence from MxB sensitivity. We provide evidence that MxB sensitivity depends on HIV-1 capsid conformation, rather than cofactor recruitment. We show that depleting CPSF6 to change nuclear import pathway does not impact MxB sensitivity, but mutants that recapitulate the effect of Cyclophilin A binding on capsid conformation and dynamics strongly impact MxB sensitivity. We demonstrate that HIV-1 primary isolates have different MxB sensitivities due to cytotoxic T lymphocyte (CTL) selected differences in Gag sequence but similar cofactor dependencies. Overall our work demonstrates a complex relationship between cyclophilin dependence and MxB sensitivity likely driven by CTL escape. We propose that cyclophilin binding provides conformational flexibility to HIV-1 capsid facilitating simultaneous evasion of capsid-targeting restriction factors including TRIM5 as well as MxB.
Assuntos
Capsídeo/química , HIV-1/fisiologia , Proteínas de Resistência a Myxovirus/química , Transporte Ativo do Núcleo Celular , HIV-1/química , HumanosRESUMO
Microglia exhibit multiple, phenotype-dependent motility patterns often triggered by purinergic stimuli. However, little data exist on motility of human microglia in pathological situations. Here we examine motility of microglia stained with a fluorescent lectin in tissue slices from female and male epileptic patients diagnosed with mesial temporal lobe epilepsy or cortical glioma (peritumoral cortex). Microglial shape varied from ramified to amoeboid cells predominantly in regions of high neuronal loss or closer to a tumor. Live imaging revealed unstimulated or purine-induced microglial motilities, including surveillance movements, membrane ruffling, and process extension or retraction. At different concentrations, ADP triggered opposing motilities. Low doses triggered process extension. It was suppressed by P2Y12 receptor antagonists, which also reduced process length and surveillance movements. Higher purine doses caused process retraction and membrane ruffling, which were blocked by joint application of P2Y1 and P2Y13 receptor antagonists. Purinergic effects on motility were similar for all microglia tested. Both amoeboid and ramified cells from mesial temporal lobe epilepsy or peritumoral cortex tissue expressed P2Y12 receptors. A minority of microglia expressed the adenosine A2A receptor, which has been linked with process withdrawal of rodent cells. Laser-mediated tissue damage let us test the functional significance of these effects. Moderate damage induced microglial process extension, which was blocked by P2Y12 receptor antagonists. Overall, the purine-induced motility of human microglia in epileptic tissue is similar to that of rodent microglia in that the P2Y12 receptor initiates process extension. It differs in that retraction is triggered by joint activation of P2Y1/P2Y13 receptors.SIGNIFICANCE STATEMENT Microglial cells are brain-resident immune cells with multiple functions in healthy or diseased brains. These diverse functions are associated with distinct phenotypes, including different microglial shapes. In the rodent, purinergic signaling is associated with changes in cell shape, such as process extension toward tissue damage. However, there are little data on living human microglia, especially in diseased states. We developed a reliable technique to stain microglia from epileptic and glioma patients to examine responses to purines. Low-intensity purinergic stimuli induced process extension, as in rodents. In contrast, high-intensity stimuli triggered a process withdrawal mediated by both P2Y1 and P2Y13 receptors. P2Y1/P2Y13 receptor activation has not previously been linked to microglial morphological changes.
Assuntos
Epilepsia do Lobo Temporal/fisiopatologia , Glioma/fisiopatologia , Microglia/fisiologia , Receptores Purinérgicos P2Y12/fisiologia , Receptores Purinérgicos P2Y1/fisiologia , Receptores Purinérgicos P2/fisiologia , Neoplasias Supratentoriais/fisiopatologia , Difosfato de Adenosina/farmacologia , Adulto , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Forma Celular/efeitos dos fármacos , Extensões da Superfície Celular/efeitos dos fármacos , Extensões da Superfície Celular/fisiologia , Extensões da Superfície Celular/ultraestrutura , Epilepsia do Lobo Temporal/etiologia , Epilepsia do Lobo Temporal/patologia , Feminino , Glioma/patologia , Humanos , Microscopia Intravital , Masculino , Microglia/efeitos dos fármacos , Microglia/ultraestrutura , Pessoa de Meia-Idade , Lectinas de Plantas , Agonistas Purinérgicos/farmacologia , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Neoplasias Supratentoriais/patologia , Esclerose Tuberosa/complicaçõesRESUMO
Human microglia, as those of rodents, may possess multiple functional phenotypes. Here we present protocols to determine elements of these microglial phenotypes obtained after therapeutic excision of brain tissue from patients with epilepsies of the temporal lobe and cortical gliomas. This technique permits to identify microglia, to determine their shape and expression of state-specific markers, to measure resting and induced motilities, to define a human microglial transcriptome, and to determine how it changes after a seizure.
Assuntos
Biomarcadores Tumorais , Neoplasias Encefálicas , Epilepsia do Lobo Temporal , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glioma , Microglia , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Epilepsia do Lobo Temporal/genética , Epilepsia do Lobo Temporal/metabolismo , Epilepsia do Lobo Temporal/patologia , Glioma/genética , Glioma/metabolismo , Glioma/patologia , Humanos , Microglia/metabolismo , Microglia/patologiaRESUMO
We present an approach for the measurement of time evolving electric field profiles in atmospheric pressure plasma discharges using electric field induced second harmonic generation (E-FISH). While the E-FISH effect has been known of for some time, recent advances in laser and detection technology have allowed the method to be utilized for spatial measurements of an arbitrarily applied electric field. A cylindrical lens is used to focus the femtosecond laser light to a line and an intensified charge coupled device is used for detection, allowing for one-dimensional (1D) spatial resolution on the order of â¼50 µm. Measurements have been carried out verifying the spatial resolution using a spatially periodic, localized electric field. Calibrated 1D electric field measurements have been completed with a time resolution of 500 ps in a laminar cold atmospheric pressure plasma jet with argon core flow and N2 co-flow powered by a nanosecond (ns) pulse dielectric barrier discharge. The field was shown to propagate as an ionization wave, with a velocity of â¼0.3 mm/ns.
RESUMO
Lipid homeostasis is dysregulated in some neurodegenerative diseases and after brain injuries due to excess glutamate or lack of oxygen. However the kinetics and cell specificity of dysregulation in different groups of lipids during excitotoxic neuronal death are not clear. Here we examined the changes during excitotoxic neuronal death induced by injecting kainic acid (KA) into the CA1 region of mouse hippocampus. We compared neuronal loss and glial cell proliferation with changes in lipid-related transcripts and markers for different lipid groups, over 12 days after KA-treatment. As neurons showed initial signs of damage, transcripts and proteins linked to fatty acid oxidation were up-regulated. Cholesterol biosynthesis induced by transcripts controlled by the transcription factor Srebp2 seems to be responsible for a transient increase in neuronal free cholesterol at 1 to 2 days. In microglia, but not in neurons, Perilipin-2 associated lipid droplets were induced and properties of Nile red emissions suggest lipid contents change over time. After microglial expression of phagocytotic markers at 2 days, some neutral lipid deposits co-localized with lysosome markers of microglia and were detected within putative phagocytotic cups. These data delineate distinct lipid signals in neurons and glial cells during excitotoxic processes from initial neuronal damage to engagement of the lysosome-phagosome system.
Assuntos
Região CA1 Hipocampal/metabolismo , Perfilação da Expressão Gênica , Ácido Caínico/farmacologia , Gotículas Lipídicas/metabolismo , Lipídeos de Membrana/metabolismo , Microglia/metabolismo , Degeneração Neural/metabolismo , Neurônios/metabolismo , Animais , Biomarcadores/metabolismo , Região CA1 Hipocampal/citologia , Região CA1 Hipocampal/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Colesterol/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microscopia Eletrônica , Microscopia de Fluorescência por Excitação Multifotônica , Degeneração Neural/induzido quimicamente , Degeneração Neural/patologia , Neurônios/efeitos dos fármacos , Regulação para CimaRESUMO
A zero-dimensional kinetics simulation of femtosecond laser ionization in nitrogen is proposed that includes fast gas heating effects, electron scattering (elastic and inelastic) rate coefficients from BOLSIG+ and photoionization based on filamentation theory. Key rate coefficients possessing significant uncertainty are tuned (within the range of variation found in literature) to reproduce the time-varying signal acquired by a bandpass-filtered photomultiplier tube with good agreement up to several hundred nanoseconds. Separate spectral measurements calibrate the relative strength of signal components. Derived equations relate the model to experimental measurements in absolute units. Reactions contributing to the rate of change of important species are displayed in terms of absolute rate and relative fraction. In general, decreasing the gas density lengthens the duration of early reactions and delays the start of later reactions. The model agrees with data taken in a variable temperature and pressure free jet by an intensified camera. Results demonstrate that initial signal depends primarily on gas density and secondarily on gas temperature. The optimal (maximum) initial signal occurs at a gas density below atmospheric. Decreases in gas density alter the evolution of excited-state populations, postponing the peak (while reducing its value) and slowing the rate of decay. For the optimal case, populations are favorably shifted in time with respect to the gate delay (and width) to boost the signal. Reductions in gas temperature generally enhance initial signal due to elevated dissociative recombination of cluster ions (along with excited-state coupling from quenching and energy pooling).
RESUMO
Femtosecond laser tagging is demonstrated for the first time in R134a (1,1,1,2-Tetrafluoroethane) gas, and in mixtures of R134a with small quantities of air. A systematic study of this tagging method is explored through the adjustment of gas pressure, mixture ratio and laser properties. It is found that the signal strength and lifetime are greatest at low pressures for excitation at both the 400 nm and 800 nm laser wavelengths. The relative intensities of two spectral peaks in the near-UV emission change as a function of gas pressure and can potentially be used for local pressure measurements. Single shot precision in pure R134a and R134a with 5% air is demonstrated in quiescent gas and at the exit of a subsonic pipe flow. One standard deviation (68%) of the uncertainty lies within 5 m/s of the mean velocity in a low pressure quiescent flow using a delay time of 3µs, and 18 m/s in a 230 m/s flow using a delay of 5 µs. The parameter space of these results are chosen to mimic conditions used in the NASA Langley Research Center's Transonic Dynamics Tunnel. The precision and signal lifetime demonstrate the feasibility of using this technique for measuring flowfields that induce airfoil flutter.
RESUMO
Microglia, the immune cells of the brain, are highly plastic and possess multiple functional phenotypes. Differences in phenotype in different regions and different states of epileptic human brain have been little studied. Here we use transcriptomics, anatomy, imaging of living cells and ELISA measurements of cytokine release to examine microglia from patients with temporal lobe epilepsies. Two distinct microglial phenotypes were explored. First we asked how microglial phenotype differs between regions of high and low neuronal loss in the same brain. Second, we asked how microglial phenotype is changed by a recent seizure. In sclerotic areas with few neurons, microglia have an amoeboid rather than ramified shape, express activation markers and respond faster to purinergic stimuli. The repairing interleukin, IL-10, regulates the basal phenotype of microglia in the CA1 and CA3 regions with neuronal loss and gliosis. To understand changes in phenotype induced by a seizure, we estimated the delay from the last seizure until tissue collection from changes in reads for immediate early gene transcripts. Pseudotime ordering of these data was validated by comparison with results from kainate-treated mice. It revealed a local and transient phenotype in which microglia secrete the human interleukin CXCL8, IL-1B and other cytokines. This secretory response is mediated in part via the NRLP3 inflammasome.
Assuntos
Encéfalo/imunologia , Encéfalo/patologia , Epilepsia do Lobo Temporal/imunologia , Epilepsia do Lobo Temporal/patologia , Microglia/patologia , Adulto , Idoso , Animais , Epilepsia do Lobo Temporal/metabolismo , Feminino , Humanos , Interleucina-10/metabolismo , Masculino , Camundongos , Microglia/metabolismo , Pessoa de Meia-Idade , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fenótipo , Transcriptoma , Adulto JovemRESUMO
Pharmacoresistant epilepsy is a common neurological disorder in which increased neuronal intrinsic excitability and synaptic excitation lead to pathologically synchronous behavior in the brain. In the majority of experimental and theoretical epilepsy models, epilepsy is associated with reduced inhibition in the pathological neural circuits, yet effects of intrinsic excitability are usually not explicitly analyzed. Here we present a novel neural mass model that includes intrinsic excitability in the form of spike-frequency adaptation in the excitatory population. We validated our model using local field potential (LFP) data recorded from human hippocampal/subicular slices. We found that synaptic conductances and slow adaptation in the excitatory population both play essential roles for generating seizures and pre-ictal oscillations. Using bifurcation analysis, we found that transitions towards seizure and back to the resting state take place via Andronov-Hopf bifurcations. These simulations therefore suggest that single neuron adaptation as well as synaptic inhibition are responsible for orchestrating seizure dynamics and transition towards the epileptic state.
Assuntos
Adaptação Fisiológica/fisiologia , Epilepsia/fisiopatologia , Sistema Límbico/fisiopatologia , Convulsões/fisiopatologia , Adolescente , Adulto , Eletroencefalografia/métodos , Epilepsia/patologia , Feminino , Hipocampo/patologia , Hipocampo/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Neurológicos , Neurônios/fisiologia , Convulsões/patologia , Adulto JovemRESUMO
The presubiculum contains head direction cells that are crucial for spatial orientation. Here, we examined the connectivity and strengths of thalamic inputs to presubicular layer 3 neurons projecting to the medial entorhinal cortex in the mouse. We recorded pairs of projection neurons and interneurons while optogenetically stimulating afferent fibers from the anterior thalamic nuclei. Thalamic input differentially affects presubicular neurons: layer 3 pyramidal neurons and fast-spiking parvalbumin-expressing interneurons are directly and monosynaptically activated, with depressing dynamics, whereas somatostatin-expressing interneurons are indirectly excited, during repetitive anterior thalamic nuclei activity. This arrangement ensures that the thalamic excitation of layer 3 cells is often followed by disynaptic inhibition. Feedforward inhibition is largely mediated by parvalbumin interneurons, which have a high probability of connection to presubicular pyramidal cells, and it may enforce temporally precise head direction tuning during head turns. Our data point to the potential contribution of presubicular microcircuits for fine-tuning thalamic head direction signals transmitted to medial entorhinal cortex.SIGNIFICANCE STATEMENT How microcircuits participate in shaping neural inputs is crucial to understanding information processing in the brain. Here, we show how the presubiculum may process thalamic head directional information before transmitting it to the medial entorhinal cortex. Synaptic inputs from the anterior thalamic nuclei excite layer 3 pyramidal cells and parvalbumin interneurons, which mediate disynaptic feedforward inhibition. Somatostatin interneurons are excited indirectly. Presubicular circuits may switch between two regimens depending on the angular velocity of head movements. During immobility, somatostatin-pyramidal cell interactions could support maintained head directional firing with attractor-like dynamics. During rapid head turns, in contrast, parvalbumin-mediated feedforward inhibition may act to tune the head direction signal transmitted to medial entorhinal cortex.