scholarly journals Impaired Interval Timing and Spatial–Temporal Integration in Mice Deficient in CHL1, a Gene Associated with Schizophrenia

2013 ◽  
Vol 1 (1) ◽  
pp. 21-38 ◽  
Author(s):  
Mona Buhusi ◽  
Ioana Scripa ◽  
Christina L. Williams ◽  
Catalin V. Buhusi
Keyword(s):  
Spatial Information ◽  
Neurodevelopmental Disorder ◽  
Temporal Integration ◽  
Gene Mutations ◽  
Interval Timing ◽  
Reference Memory ◽  
Synaptic Function ◽  
Temporal Information ◽  
Adult Brain ◽  
Central Platform

Interval timing is crucial for decision-making and motor control and is impaired in many neuropsychiatric disorders, including schizophrenia — a neurodevelopmental disorder with a strong genetic component. Several gene mutations, polymorphisms or rare copy number variants have been associated with schizophrenia. L1 cell adhesion molecules (L1CAMs) are involved in neurodevelopmental processes, and in synaptic function and plasticity in the adult brain. Mice deficient in the Close Homolog to L1 (CHL1) adhesion molecule show alterations of hippocampal and thalamo-cortical neuroanatomy as well as deficits in sensorimotor gating and exploratory behavior. We analyzed interval timing and attentional control of temporal and spatial information in male CHL1 deficient (KO) mice and wild type (WT) controls. In a 20-s peak-interval timing procedure (standard and reversed), KO mice showed a maintained leftward shift of the response function relative to WT, indicative of a deficit in memory encoding/decoding. In trials with 2, 5, or 10-s gaps, KO mice shifted their peak times less than WT controls at longer gap durations, suggesting a decreased (attentional) effect of interruptions. In the spatial–temporal task, KO mice made more working and reference memory errors than controls, suggestive of impaired use of spatial and/or temporal information. When the duration spent on the central platform of the maze was manipulated, WT mice showed fewer spatial errors at the trained duration than at shorter or longer durations, indicative of discrimination based upon spatial–temporal integration. In contrast, performance was similar at all tested durations in KO mice, indicative of control by spatial cues, but not by temporal cues. These results suggest that CHL1 KO mice selectively attend to the more relevant cues of the task, and fail to integrate more complex spatial–temporal information, possibly as a result of reduced memory capacity related to hippocampal impairment, and altered temporal-integration mechanisms possibly due to thalamo-cortical anomalies.

scholarly journals The Role of Spatio-Temporal Information to Govern the COVID-19 Pandemic: A European Perspective

2021 ◽  
Vol 10 (3) ◽  
pp. 166
Author(s):  
Hartmut Müller ◽  
Marije Louwsma
Keyword(s):  
European Union ◽  
Spatial Distribution ◽  
Spatial Information ◽  
National Level ◽  
Temporal Information ◽  
The European Union ◽  
Member States ◽  
Heavy Burden ◽  
Spatio Temporal

The Covid-19 pandemic put a heavy burden on member states in the European Union. To govern the pandemic, having access to reliable geo-information is key for monitoring the spatial distribution of the outbreak over time. This study aims to analyze the role of spatio-temporal information in governing the pandemic in the European Union and its member states. The European Nomenclature of Territorial Units for Statistics (NUTS) system and selected national dashboards from member states were assessed to analyze which spatio-temporal information was used, how the information was visualized and whether this changed over the course of the pandemic. Initially, member states focused on their own jurisdiction by creating national dashboards to monitor the pandemic. Information between member states was not aligned. Producing reliable data and timeliness reporting was problematic, just like selecting indictors to monitor the spatial distribution and intensity of the outbreak. Over the course of the pandemic, with more knowledge about the virus and its characteristics, interventions of member states to govern the outbreak were better aligned at the European level. However, further integration and alignment of public health data, statistical data and spatio-temporal data could provide even better information for governments and actors involved in managing the outbreak, both at national and supra-national level. The Infrastructure for Spatial Information in Europe (INSPIRE) initiative and the NUTS system provide a framework to guide future integration and extension of existing systems.

scholarly journals Loss of Non-Apoptotic Role of Caspase-3 in the PINK1 Mouse Model of Parkinson’s Disease

2019 ◽  
Vol 20 (14) ◽  
pp. 3407 ◽  
Author(s):  
Paola Imbriani ◽  
Annalisa Tassone ◽  
Maria Meringolo ◽  
Giulia Ponterio ◽  
Graziella Madeo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Synaptic Plasticity ◽  
Mouse Model ◽  
Caspase 3 ◽  
Cysteine Proteases ◽  
Synaptic Function ◽  
Adult Brain ◽  
Striatal Slices

Caspases are a family of conserved cysteine proteases that play key roles in multiple cellular processes, including programmed cell death and inflammation. Recent evidence shows that caspases are also involved in crucial non-apoptotic functions, such as dendrite development, axon pruning, and synaptic plasticity mechanisms underlying learning and memory processes. The activated form of caspase-3, which is known to trigger widespread damage and degeneration, can also modulate synaptic function in the adult brain. Thus, in the present study, we tested the hypothesis that caspase-3 modulates synaptic plasticity at corticostriatal synapses in the phosphatase and tensin homolog (PTEN) induced kinase 1 (PINK1) mouse model of Parkinson’s disease (PD). Loss of PINK1 has been previously associated with an impairment of corticostriatal long-term depression (LTD), rescued by amphetamine-induced dopamine release. Here, we show that caspase-3 activity, measured after LTD induction, is significantly decreased in the PINK1 knockout model compared with wild-type mice. Accordingly, pretreatment of striatal slices with the caspase-3 activator α-(Trichloromethyl)-4-pyridineethanol (PETCM) rescues a physiological LTD in PINK1 knockout mice. Furthermore, the inhibition of caspase-3 prevents the amphetamine-induced rescue of LTD in the same model. Our data support a hormesis-based double role of caspase-3; when massively activated, it induces apoptosis, while at lower level of activation, it modulates physiological phenomena, like the expression of corticostriatal LTD. Exploring the non-apoptotic activation of caspase-3 may contribute to clarify the mechanisms involved in synaptic failure in PD, as well as in view of new potential pharmacological targets.

scholarly journals Interval Timing by Long-Range Temporal Integration

2011 ◽  
Vol 5 ◽  
Author(s):  
Patrick Simen ◽  
Fuat Balci ◽  
Laura deSouza ◽  
Jonathan D. Cohen ◽  
Philip Holmes
Keyword(s):  
Long Range ◽  
Temporal Integration ◽  
Interval Timing

scholarly journals A time-stamp mechanism may provide temporal information necessary for egocentric to allocentric spatial transformations

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Avner Wallach ◽  
Erik Harvey-Girard ◽  
James Jaeyoon Jun ◽  
André Longtin ◽  
Len Maler
Keyword(s):  
Spatial Learning ◽  
Spatial Organization ◽  
Spatial Information ◽  
Spatial Relations ◽  
Temporal Information ◽  
Accurate Estimation ◽  
Neural Recordings ◽  
Brain Circuitry ◽  
Learning Circuits ◽  
Thalamic Region

Learning the spatial organization of the environment is essential for most animals’ survival. This requires the animal to derive allocentric spatial information from egocentric sensory and motor experience. The neural mechanisms underlying this transformation are mostly unknown. We addressed this problem in electric fish, which can precisely navigate in complete darkness and whose brain circuitry is relatively simple. We conducted the first neural recordings in the preglomerular complex, the thalamic region exclusively connecting the optic tectum with the spatial learning circuits in the dorsolateral pallium. While tectal topographic information was mostly eliminated in preglomerular neurons, the time-intervals between object encounters were precisely encoded. We show that this reliable temporal information, combined with a speed signal, can permit accurate estimation of the distance between encounters, a necessary component of path-integration that enables computing allocentric spatial relations. Our results suggest that similar mechanisms are involved in sequential spatial learning in all vertebrates.

A two-stream network with joint spatial-temporal distance for video-based person re-identification

2020 ◽  
Vol 39 (3) ◽  
pp. 3769-3781
Author(s):  
Zhisong Han ◽  
Yaling Liang ◽  
Zengqun Chen ◽  
Zhiheng Zhou
Keyword(s):  
Spatial Information ◽  
Temporal Information ◽  
Temporal Distance ◽  
Spatial Distance ◽  
Weighted Sum ◽  
Stream Network ◽  
Spatial Features ◽  
Public Datasets ◽  
Types Of Information ◽  
Temporal Information Extraction

Video-based person re-identification aims to match videos of pedestrians captured by non-overlapping cameras. Video provides spatial information and temporal information. However, most existing methods do not combine these two types of information well and ignore that they are of different importance in most cases. To address the above issues, we propose a two-stream network with a joint distance metric for measuring the similarity of two videos. The proposed two-stream network has several appealing properties. First, the spatial stream focuses on multiple parts of a person and outputs robust local spatial features. Second, a lightweight and effective temporal information extraction block is introduced in video-based person re-identification. In the inference stage, the distance of two videos is measured by the weighted sum of spatial distance and temporal distance. We conduct extensive experiments on four public datasets, i.e., MARS, PRID2011, iLIDS-VID and DukeMTMC-VideoReID to show that our proposed approach outperforms existing methods in video-based person re-ID.

scholarly journals L-type voltage-gated calcium channel regulation of in vitro human cortical neuronal networks

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
William Plumbly ◽  
Nick Brandon ◽  
Tarek Z. Deeb ◽  
Jeremy Hall ◽  
Adrian J. Harwood
Keyword(s):  
Calcium Channel ◽  
Neuronal Networks ◽  
Gene Mutations ◽  
Synaptic Function ◽  
Neuronal Firing ◽  
Network Activity ◽  
Electrode Arrays ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channel

Abstract The combination of in vitro multi-electrode arrays (MEAs) and the neuronal differentiation of stem cells offers the capability to study human neuronal networks from patient or engineered human cell lines. Here, we use MEA-based assays to probe synaptic function and network interactions of hiPSC-derived neurons. Neuronal network behaviour first emerges at approximately 30 days of culture and is driven by glutamate neurotransmission. Over a further 30 days, inhibitory GABAergic signalling shapes network behaviour into a synchronous regular pattern of burst firing activity and low activity periods. Gene mutations in L-type voltage gated calcium channel subunit genes are strongly implicated as genetic risk factors for the development of schizophrenia and bipolar disorder. We find that, although basal neuronal firing rate is unaffected, there is a dose-dependent effect of L-type voltage gated calcium channel inhibitors on synchronous firing patterns of our hiPSC-derived neural networks. This demonstrates that MEA assays have sufficient sensitivity to detect changes in patterns of neuronal interaction that may arise from hypo-function of psychiatric risk genes. Our study highlights the utility of in vitro MEA based platforms for the study of hiPSC neural network activity and their potential use in novel compound screening.

Angelman Syndrome

2017 ◽  
Author(s):  
Kristin W. Barañano
Keyword(s):  
Angelman Syndrome ◽  
Expressive Language ◽  
Neurodevelopmental Disorder ◽  
Synaptic Function ◽  
Gait Disorder ◽  
Ataxic Gait ◽  
Synaptic Circuits ◽  
Ubiquitin E3 Ligase ◽  
Time Treatment

Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by maternal deficiency of the epigenetically imprinted gene UBE3A. It is characterized by severe developmental delay, an ataxic gait disorder, an apparent happy demeanor with frequent smiling or laughing, and severe expressive language impairments. Understanding the neurobiology of AS has focused on understanding how UBE3A is regulated by neuronal activity, as well as the targets of its ubiquitin E3 ligase activity. This has led to a model of the role of UBE3A in the regulation of experience-dependent sculpting of synaptic circuits. At this time, treatment is largely supportive, but efforts directed toward reversing the epigenetic silencing machinery may lead to improved synaptic function in AS patients.

Effect of Acute Physical Activity on Interval Timing

2018 ◽  
Vol 6 (1) ◽  
pp. 14-31 ◽  
Author(s):  
Ceyda Sayalı ◽  
Ezgi Uslu ◽  
Melisa Menceloğlu ◽  
Reşit Canbeyli ◽  
Fuat Balcı
Keyword(s):  
Physical Activity ◽  
Temporal Integration ◽  
Interval Timing ◽  
Subjective Time ◽  
Reproduction Task ◽  
Movement Condition ◽  
Temporal Reproduction ◽  
Long Term Performance ◽  
Term Performance ◽  
Larger Sample

Timing is an integral part of physical activities. Walking as a routine form of physical activity might affect interval timing primarily in two different ways within the pacemaker–accumulator timing-theoretic framework: (1) by increasing the speed of the pacemaker due to its physiological effects; (2) by decreasing attention to time and consequently slowing the rate of temporal integration by serving as a secondary task. In order to elucidate the effect of movement on subjective time, in two different experiments we employed a temporal reproduction task conducted on the treadmill under four different encoding–decoding conditions: (1) encoding and reproducing (decoding) the duration while standing (rest); (2) encoding the duration at rest and reproducing it while moving: (3) both encoding and reproducing the duration while moving; and (4) encoding the duration while moving and reproducing it at rest. In the first experiment, participants were tested either in the 4 or the 8 km/h movement condition, whereas in the second experiment a larger sample was tested only in the 4 km/h movement condition. Data were de-trended to control for long-term performance drifts. In Experiment 1, overall durations encoded at rest and reproduced during motion were under-reproduced whereas durations encoded during motion and reproduced at rest were over-reproduced only in the 8 km/h condition. In Experiment 2, the same results were observed in the 4 km/h condition with a larger sample size. These effects on timing behavior provide support for the clock speed-driven effect of movement and contradicts the predictions of attention-based mediation.

Enhanced Hypoxia Susceptibility in Hippocampal Slices From a Mouse Model of Rett Syndrome

2009 ◽  
Vol 101 (2) ◽  
pp. 1016-1032 ◽  
Author(s):  
Marc Fischer ◽  
Julia Reuter ◽  
Florian J. Gerich ◽  
Belinda Hildebrandt ◽  
Sonja Hägele ◽  
...  
Keyword(s):  
Rett Syndrome ◽  
Molecular Mechanisms ◽  
Pyramidal Neurons ◽  
Neurodevelopmental Disorder ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Synaptic Function ◽  
Cell Swelling ◽  
Arterial Oxygen ◽  
Ca1 Pyramidal Neurons

Rett syndrome is a neurodevelopmental disorder caused by mutations in the X-chromosomal MECP2 gene encoding for the transcriptional regulator methyl CpG binding protein 2 (MeCP2). Rett patients suffer from episodic respiratory irregularities and reduced arterial oxygen levels. To elucidate whether such intermittent hypoxic episodes induce adaptation/preconditioning of the hypoxia-vulnerable hippocampal network, we analyzed its responses to severe hypoxia in adult Rett mice. The occurrence of hypoxia-induced spreading depression (HSD)—an experimental model for ischemic stroke—was hastened in Mecp2− /y males. The extracellular K+ rise during HSD was attenuated in Mecp2− /y males and the input resistance of CA1 pyramidal neurons decreased less before HSD onset. CA1 pyramidal neurons were smaller and more densely packed, but the cell swelling during HSD was unaffected. The intrinsic optical signal and the propagation of HSD were similar among the different genotypes. Basal synaptic function was intact, but Mecp2− /y males showed reduced paired-pulse facilitation and higher field potential/fiber volley ratios, but no increased seizure susceptibility. Synaptic failure during hypoxia was complete in all genotypes and the final degree of posthypoxic synaptic recovery indistinguishable. Cellular ATP content was normal in Mecp2− /y males, but their hematocrit was increased as was HIF-1α expression throughout the brain. This is the first study showing that in Rett syndrome, the susceptibility of telencephalic neuronal networks to hypoxia is increased; the underlying molecular mechanisms apparently involve disturbed K+ channel function. Such an increase in hypoxia susceptibility may potentially contribute to the vulnerability of male Rett patients who are either not viable or severely disabled.

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