177 research outputs found

    Population-level neural correlates of flexible avoidance learning in medial prefrontal cortex

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    The medial prefrontal cortex (mPFC) has been proposed to link sensory inputs and behavioral outputs to mediate the execution of learned behaviors. However, how such a link is implemented has remained unclear. To measure prefrontal neural correlates of sensory stimuli and learned behaviors, we performed population calcium imaging during a novel tone-signaled active avoidance paradigm in mice. We developed a novel analysis approach based on dimensionality reduction and decoding that allowed us to identify and isolate population activity patterns related the tone stimulus, learned avoidance actions and general motion. While tone-related activity was not informative about behavior, avoidance-related activity was predictive of upcoming avoidance actions. Moreover, avoidance-related activity distinguished between two different learned avoidance actions, consistent with a model in which mPFC contributes to the selection between different goal-directed actions. Overall, our results suggest that mPFC circuit dynamics transform sensory inputs into specific behavioral outputs through distributed population-level computations

    SARS-CoV-2 viral shedding and transmission dynamics : implications of WHO COVID-19 discharge guidelines

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    This work was supported through the Alliance for Accelerating Excellence in Science in Africa (AESA), a funding, agenda-setting, programme management initiative of the African Academy of Sciences (AAS), the African- Union Development Agency (AUDA-NEPAD), founding and funding global partners and through a resolution of the summit of African Union Heads of Governments.The evolving nature of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has necessitated periodic revisions of COVID-19 patient treatment and discharge guidelines. Since the identification of the first COVID-19 cases in November 2019, the World Health Organization (WHO) has played a crucial role in tackling the country-level pandemic preparedness and patient management protocols. Among others, the WHO provided a guideline on the clinical management of COVID-19 patients according to which patients can be released from isolation centers on the 10th day following clinical symptom manifestation, with a minimum of 72 additional hours following the resolution of symptoms. However, emerging direct evidence indicating the possibility of viral shedding 14 days after the onset of symptoms called for evaluation of the current WHO discharge recommendations. In this review article, we carried out comprehensive literature analysis of viral shedding with specific focus on the duration of viral shedding and infectivity in asymptomatic and symptomatic (mild, moderate, and severe forms) COVID-19 patients. Our literature search indicates that even though, there are specific instances where the current protocols may not be applicable ( such as in immune-compromised patients there is no strong evidence to contradict the current WHO discharge criteria.Publisher PDFPeer reviewe

    Direct Observation of Propagating Gigahertz Coherent Guided Acoustic Phonons in Free Standing Single Copper Nanowires

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    We report on gigahertz acoustic phonon waveguiding in free-standing single copper nanowires studied by femtosecond transient reflectivity measurements. The results are discussed on the basis of the semianalytical resolution of the Pochhammer and Chree equation. The spreading of the generated Gaussian wave packet of two different modes is derived analytically and compared with the observed oscillations of the sample reflectivity. These experiments provide a unique way to independently obtain geometrical and material characterization. This direct observation of coherent guided acoustic phonons in a single nano-object is also the first step toward nanolateral size acoustic transducer and comprehensive studies of the thermal properties of nanowires

    Ab initio Pseudopotential Plane-wave Calculations of the Electronic Structure of YBa_2Cu_3O_7

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    We present an ab initio pseudopotential local density functional calculation for stoichiometric high-Tc cuprate YBa_2Cu_3O_7 using the plane-wave basis set. We have overcome well-known difficulties in applying pseudopotential methods to first-row elements, transition metals, and rare-earth materials by carefully generating norm-conserving pseudopotentials with excellent transferability and employing an extremely efficient iterative diagonalization scheme optimized for our purpose. The self-consistent band structures, the total and site-projected densities of states, the partial charges and their symmetry-decompositions, and some characteristic charge densities near E_f are presented. We compare our results with various existing (F)LAPW and (F)LMTO calculations and establish that the ab initio pseudopotential method is competitive with other methods in studying the electronic structure of such complicated materials as high-Tc cuprates. [8 postscript files in uuencoded compressed form]Comment: 14 pages, RevTeX v3.0, 8 figures (appended in postscript file), SNUTP 94-8

    TOM40 Mediates Mitochondrial Dysfunction Induced by α-Synuclein Accumulation in Parkinson's Disease.

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    Alpha-synuclein (α-Syn) accumulation/aggregation and mitochondrial dysfunction play prominent roles in the pathology of Parkinson's disease. We have previously shown that postmortem human dopaminergic neurons from PD brains accumulate high levels of mitochondrial DNA (mtDNA) deletions. We now addressed the question, whether alterations in a component of the mitochondrial import machinery -TOM40- might contribute to the mitochondrial dysfunction and damage in PD. For this purpose, we studied levels of TOM40, mtDNA deletions, oxidative damage, energy production, and complexes of the respiratory chain in brain homogenates as well as in single neurons, using laser-capture-microdissection in transgenic mice overexpressing human wildtype α-Syn. Additionally, we used lentivirus-mediated stereotactic delivery of a component of this import machinery into mouse brain as a novel therapeutic strategy. We report here that TOM40 is significantly reduced in the brain of PD patients and in α-Syn transgenic mice. TOM40 deficits were associated with increased mtDNA deletions and oxidative DNA damage, and with decreased energy production and altered levels of complex I proteins in α-Syn transgenic mice. Lentiviral-mediated overexpression of Tom40 in α-Syn-transgenic mice brains ameliorated energy deficits as well as oxidative burden. Our results suggest that alterations in the mitochondrial protein transport machinery might contribute to mitochondrial impairment in α-Synucleinopathies

    SARS-CoV-2 Viral Shedding and Transmission Dynamics: Implications of WHO COVID-19 Discharge Guidelines

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    The evolving nature of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has necessitated periodic revisions of COVID-19 patient treatment and discharge guidelines. Since the identification of the first COVID-19 cases in November 2019, the World Health Organization (WHO) has played a crucial role in tackling the country-level pandemic preparedness and patient management protocols. Among others, the WHO provided a guideline on the clinical management of COVID-19 patients according to which patients can be released from isolation centers on the 10th day following clinical symptom manifestation, with a minimum of 72 additional hours following the resolution of symptoms. However, emerging direct evidence indicating the possibility of viral shedding 14 days after the onset of symptoms called for evaluation of the current WHO discharge recommendations. In this review article, we carried out comprehensive literature analysis of viral shedding with specific focus on the duration of viral shedding and infectivity in asymptomatic and symptomatic (mild, moderate, and severe forms) COVID-19 patients. Our literature search indicates that even though, there are specific instances where the current protocols may not be applicable ( such as in immune-compromised patients there is no strong evidence to contradict the current WHO discharge criteria

    Efficient Temporal Processing of Naturalistic Sounds

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    In this study, we investigate the ability of the mammalian auditory pathway to adapt its strategy for temporal processing under natural stimulus conditions. We derive temporal receptive fields from the responses of neurons in the inferior colliculus to vocalization stimuli with and without additional ambient noise. We find that the onset of ambient noise evokes a change in receptive field dynamics that corresponds to a change from bandpass to lowpass temporal filtering. We show that these changes occur within a few hundred milliseconds of the onset of the noise and are evident across a range of overall stimulus intensities. Using a simple model, we illustrate how these changes in temporal processing exploit differences in the statistical properties of vocalizations and ambient noises to increase the information in the neural response in a manner consistent with the principles of efficient coding

    Feedforward Inhibition and Synaptic Scaling – Two Sides of the Same Coin?

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    Feedforward inhibition and synaptic scaling are important adaptive processes that control the total input a neuron can receive from its afferents. While often studied in isolation, the two have been reported to co-occur in various brain regions. The functional implications of their interactions remain unclear, however. Based on a probabilistic modeling approach, we show here that fast feedforward inhibition and synaptic scaling interact synergistically during unsupervised learning. In technical terms, we model the input to a neural circuit using a normalized mixture model with Poisson noise. We demonstrate analytically and numerically that, in the presence of lateral inhibition introducing competition between different neurons, Hebbian plasticity and synaptic scaling approximate the optimal maximum likelihood solutions for this model. Our results suggest that, beyond its conventional use as a mechanism to remove undesired pattern variations, input normalization can make typical neural interaction and learning rules optimal on the stimulus subspace defined through feedforward inhibition. Furthermore, learning within this subspace is more efficient in practice, as it helps avoid locally optimal solutions. Our results suggest a close connection between feedforward inhibition and synaptic scaling which may have important functional implications for general cortical processing
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