The Continuity of Context: A Role for the Hippocampus

Tracking moment-to-moment change in input, and detecting change sufficient to require altering behavior is crucial to survival. We discuss how the brain evaluates change over time, focusing on hippocampus and its role in tracking context. We leverage the anatomy and physiology of the hippocampal longitudinal axis, re-entrant loops, and amorphous networks, to account for stimulus equivalence and the updating of an organism’s sense of its context. Place cells play a central role in tracking contextual continuities and discontinuities across multiple scales, a capacity beyond current models of pattern separation and completion. This perspective highlights the critical role of the hippocampus in both spatial cognition and episodic memory: tracking change and detecting boundaries separating one context, or episode, from another.

Characterizing spatial structures of larval fish assemblages at multiple scales in relation to environmental heterogeneity in the Strait of Georgia (British Columbia, Canada)

Canadian Journal of Fisheries and Aquatic Sciences ◽

10.1139/cjfas-2017-0194 ◽

2018 ◽

Vol 75 (11) ◽

pp. 1902-1914 ◽

Cited By ~ 1

Author(s):

Lu Guan ◽

John F. Dower ◽

Pierre Pepin

Keyword(s):

British Columbia ◽

Environmental Heterogeneity ◽

Multiple Scales ◽

Larval Fish ◽

Critical Role ◽

Multiscale Approach ◽

Spatial Structures ◽

Strait Of Georgia ◽

Medium Scale

Spatial structures of larval fish in the Strait of Georgia (British Columbia, Canada) were quantified in the springs of 2009 and 2010 to investigate linkages to environmental heterogeneity at multiple scales. By applying a multiscale approach, principal coordinate neighborhood matrices, spatial variability was decomposed into three predefined scale categories: broad scale (>40 km), medium scale (20∼40 km), and fine scale (<20 km). Spatial variations in larval density of the three dominant fish taxa with different early life histories (Pacific herring (Clupea pallasii), Pacific hake (Merluccius productus), and northern smoothtongue (Leuroglossus schmidti)) were mainly structured at broad and medium scales, with scale-dependent associations with environmental descriptors varying interannually and among species. Larval distributions in the central-southern Strait were mainly associated with salinity, temperature, and vertical stability of the top 50 m of the water column on the medium scale. Our results emphasize the critical role of local estuarine circulation, especially at medium spatial scale, in structuring hierarchical spatial distributions of fish larvae in the Strait of Georgia and suggest the role of fundamental differences in life-history traits in influencing the formation and maintenance of larval spatial structures.

A critical role for central vasopressin in regulation of fever during bacterial infection

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1992.263.6.r1235 ◽

1992 ◽

Vol 263 (6) ◽

pp. R1235-R1240

Author(s):

R. A. Cridland ◽

N. W. Kasting

Keyword(s):

Body Temperature ◽

Arginine Vasopressin ◽

Continuous Measurement ◽

Critical Role ◽

Experimental Models ◽

Bacterial Endotoxins ◽

Chronic Infusion ◽

Live Bacteria ◽

Previous investigations on the antipyretic properties of arginine vasopressin have used bacterial endotoxins or pyrogens to induce fever. Because these experimental models of fever fail to mimic all aspects of the responses to infection, we felt it was important to examine the role of endogenously released vasopressin as a neuromodulator in febrile thermoregulation during infection. Therefore the present study examines the effects of chronic infusion of a V1-receptor antagonist or saline (via osmotic minipumps into the ventral septal area of the brain) on a fever induced by injection of live bacteria. Telemetry was used for continuous measurement of body temperature in the awake unhandled rat. Animals infused with the V1-antagonist exhibited fevers that were greater in duration compared with those of saline-infused animals. These results support the hypothesis that vasopressin functions as an antipyretic agent or fever-reducing agent in brain. Importantly, they suggest that endogenously released vasopressin may play a role as a neuromodulator in natural fever.

Time-resolved neural reinstatement and pattern separation during memory decisions in human hippocampus

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1717088115 ◽

2018 ◽

Vol 115 (31) ◽

pp. E7418-E7427 ◽

Cited By ~ 17

Author(s):

Lynn J. Lohnas ◽

Katherine Duncan ◽

Werner K. Doyle ◽

Thomas Thesen ◽

Orrin Devinsky ◽

...

Keyword(s):

Critical Role ◽

Pattern Separation ◽

Time Resolved ◽

Memory Processing ◽

Fine Grained ◽

Human Hippocampus ◽

Hippocampal Activity ◽

High Frequency Activity ◽

Occipitotemporal Cortex

Mnemonic decision-making has long been hypothesized to rely on hippocampal dynamics that bias memory processing toward the formation of new memories or the retrieval of old ones. Successful memory encoding may be best optimized by pattern separation, whereby two highly similar experiences can be represented by underlying neural populations in an orthogonal manner. By contrast, successful memory retrieval is thought to be supported by a recovery of the same neural pattern laid down during encoding. Here we examined how hippocampal pattern completion and separation emerge over time during memory decisions. We measured electrocorticography activity in the human hippocampus and posterior occipitotemporal cortex (OTC) while participants performed continuous recognition of items that were new, repeated (old), or highly similar to a prior item (similar). During retrieval decisions of old items, both regions exhibited significant reinstatement of multivariate high-frequency activity (HFA) associated with encoding. Further, the extent of reinstatement of encoding patterns during retrieval was correlated with the strength (HFA power) of hippocampal encoding. Evidence for encoding pattern reinstatement was also seen in OTC on trials requiring fine-grained discrimination of similar items. By contrast, hippocampal activity showed evidence for pattern separation during these trials. Together, these results underscore the critical role of the hippocampus in supporting both reinstatement of overlapping information and separation of similar events.

Measurement and Prediction of Sound Exposure Levels by University Wind Bands

Medical Problems of Performing Artists ◽

10.21091/mppa.2010.1006 ◽

2010 ◽

Vol 25 (1) ◽

pp. 29-34 ◽

Cited By ~ 4

Author(s):

Kris Chesky

Keyword(s):

Linear Regression Analysis ◽

Critical Role ◽

Significant Proportion ◽

Sound Exposure ◽

Sound Levels ◽

Wind Bands ◽

Exposure Levels ◽

The Mean ◽

The purpose of this study was to determine sound exposure levels generated in two college wind bands. Dosimeter data from a large sample of ensemble-based instructional activities (n = 43) was collected over time and processed to assess associations with predictor variables that may be relevant to this context, including indicators of time spend at various intensity levels, maximum and peak sound levels, degree of variability of sound levels over time, and the percentage of time playing music. The mean dose per event for the entire sample was 109.5% and ranged from 53.8% to 166.9%. Results of linear regression analysis revealed that regressors accounted for a significant proportion of the variance in dose (F = 128.42, p < 0.000) and a statistically significant and very large (96% variance accounted for) contribution to the prediction of dose. Findings implicate the critical role of the instructor and teaching pedagogy.

Resilience

Genes, brain, and emotions ◽

10.1093/oso/9780198793014.003.0020 ◽

2019 ◽

pp. 286-303 ◽

Cited By ~ 1

Author(s):

Rebecca Alexander ◽

Justine Megan Gatt

Keyword(s):

Well Being ◽

Neural Systems ◽

Dynamic Interactions ◽

Control Networks ◽

Effective Interventions ◽

Adaptive Recovery ◽

The Brain ◽

Insight Into ◽

Resilience refers to the process of adaptive recovery following adversity or trauma. It is likely to include an intertwined series of dynamic interactions between neural, developmental, environmental, genetic, and epigenetic factors over time. Neuroscientific research suggests the potential role of the brain’s threat and reward systems, as well as executive control networks. Developmental research provides insight into how the environment may affect these neural systems across the lifespan towards greater risk or resilience to stress. Genetic work has revealed numerous targets that alter key neurochemical systems in the brain to influence mental health. Current challenges include ambiguities in the definition and measurement of resilience and a simplified focus on resilience as the absence of psychopathology, irrespective of levels of positive mental functioning. Greater emphasis on understanding the protective aspects of resilience and related well-being outcomes are important to delineate the unique neurobiological factors that underpin this process, so that effective interventions can be developed to assist vulnerable populations and resilience promotion.

Handbook of Research on Information Technology Management and Clinical Data Administration in Healthcare ◽

Anesthesia Information Management Systems (AIMS)

10.4018/978-1-60566-356-2.ch029 ◽

2011 ◽

pp. 465-481

Author(s):

Loren Riskin ◽

Christoph Egger-Halbeis ◽

Daniel Riskin

Keyword(s):

Operating Room ◽

Information Management ◽

Fundamental System ◽

Critical Role ◽

Management Systems ◽

Healthcare Information ◽

Operative Care ◽

Information Management Systems ◽

This chapter discusses the critical role of anesthesia information management systems (AIMS) in clinical tracking and operating room information management. It begins by reviewing the history and implementation of such systems and examines their current abilities and utilities. The current known benefits of AIMS, as documented by peer-reviewed literature, are examined. Possible additional benefits, both future and current, and the potential role of AIMS in future healthcare information management are discussed. Though AIMS vary greatly between individual systems and will continue to evolve over time, this chapter aims to highlight fundamental system features. The goal of this chapter is to broaden understanding of AIMS and their clinical utility, as they have an essential part of modern operative care.

Syk and Hrs Regulate TLR3-Mediated Antiviral Response in Murine Astrocytes

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/6927380 ◽

2019 ◽

Vol 2019 ◽

pp. 1-21 ◽

Cited By ~ 2

Author(s):

Matylda B. Mielcarska ◽

Magdalena Bossowska-Nowicka ◽

Karolina P. Gregorczyk-Zboroch ◽

Zbigniew Wyżewski ◽

Lidia Szulc-Dąbrowska ◽

...

Keyword(s):

Immune Responses ◽

Signaling Pathway ◽

Critical Role ◽

Antiviral Response ◽

Proteolytic Processing ◽

Viral Dsrna ◽

Kinase Substrate ◽

Tlr3 Signaling ◽

Toll-like receptors (TLRs) sense the presence of pathogen-associated molecular patterns. Nevertheless, the mechanisms modulating TLR-triggered innate immune responses are not yet fully understood. Complex regulatory systems exist to appropriately direct immune responses against foreign or self-nucleic acids, and a critical role of hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), endosomal sorting complex required for transportation-0 (ESCRT-0) subunit, has recently been implicated in the endolysosomal transportation of TLR7 and TLR9. We investigated the involvement of Syk, Hrs, and STAM in the regulation of the TLR3 signaling pathway in a murine astrocyte cell line C8-D1A following cell stimulation with a viral dsRNA mimetic. Our data uncover a relationship between TLR3 and ESCRT-0, point out Syk as dsRNA-activated kinase, and suggest the role for Syk in mediating TLR3 signaling in murine astrocytes. We show molecular events that occur shortly after dsRNA stimulation of astrocytes and result in Syk Tyr-342 phosphorylation. Further, TLR3 undergoes proteolytic processing; the resulting TLR3 N-terminal form interacts with Hrs. The knockdown of Syk and Hrs enhances TLR3-mediated antiviral response in the form of IFN-β, IL-6, and CXCL8 secretion. Understanding the role of Syk and Hrs in TLR3 immune responses is of high importance since activation and precise execution of the TLR3 signaling pathway in the brain seem to be particularly significant in mounting an effective antiviral defense. Infection of the brain with herpes simplex type 1 virus may increase the secretion of amyloid-β by neurons and astrocytes and be a causal factor in degenerative diseases such as Alzheimer’s disease. Errors in TLR3 signaling, especially related to the precise regulation of the receptor transportation and degradation, need careful observation as they may disclose foundations to identify novel or sustain known therapeutic targets.

Biallelic variants in the small optic lobe calpain CAPN15 are associated with congenital eye anomalies, deafness and other neurodevelopmental deficits

Human Molecular Genetics ◽

10.1093/hmg/ddaa198 ◽

2020 ◽

Vol 29 (18) ◽

pp. 3054-3063

Author(s):

Congyao Zha ◽

Carole A Farah ◽

Richard J Holt ◽

Fabiola Ceroni ◽

Lama Al-Abdi ◽

...

Keyword(s):

Optic Lobe ◽

Critical Role ◽

Genetic Diagnosis ◽

Compound Heterozygous ◽

Clinical Genetic ◽

Eye Disorders ◽

Neurodevelopmental Deficits ◽

Independent Families ◽

Abstract Microphthalmia, coloboma and cataract are part of a spectrum of developmental eye disorders in humans affecting ~12 per 100 000 live births. Currently, variants in over 100 genes are known to underlie these conditions. However, at least 40% of affected individuals remain without a clinical genetic diagnosis, suggesting variants in additional genes may be responsible. Calpain 15 (CAPN15) is an intracellular cysteine protease belonging to the non-classical small optic lobe (SOL) family of calpains, an important class of developmental proteins, as yet uncharacterized in vertebrates. We identified five individuals with microphthalmia and/or coloboma from four independent families carrying homozygous or compound heterozygous predicted damaging variants in CAPN15. Several individuals had additional phenotypes including growth deficits, developmental delay and hearing loss. We generated Capn15 knockout mice that exhibited similar severe developmental eye defects, including anophthalmia, microphthalmia and cataract, and diminished growth. We demonstrate widespread Capn15 expression throughout the brain and central nervous system, strongest during early development, and decreasing postnatally. Together, these findings demonstrate a critical role of CAPN15 in vertebrate developmental eye disorders, and may signify a new developmental pathway.

Investigating the role of dendrites in pattern separation: A computational approach

10.14293/p2199-8442.1.sop-life.pdcx4w.v1 ◽

2015 ◽

Author(s):

Spyridon Chavlis ◽

Panagiotis C. Petrantonakis ◽

Panayiota Poirazi

Keyword(s):

Granule Cells ◽

Separation Efficiency ◽

Hamming Distance ◽

Morphological Characteristics ◽

Pattern Separation ◽

Biologically Relevant ◽

Preliminary Results ◽

Neuronal Types ◽

Objectives: In order to distinguish similar memories, it is experimentally confirmed that the hippocampus forms distinct representations of them. The ability of the brain to disambiguate memories is known as pattern separation. It has been proposed that dentate gyrus (DG) accomplishes this task, specifically through its principal cells, called granule cells (GCs). In this project we investigate the role of GC dendrites in pattern separation by modifying their biophysical and morphological characteristics. Methods & Results: We have implemented a morphologically simple, yet biologically relevant, computational model of the DG that implements pattern separation. The network consists of four well-studied neuronal types: granule, mossy, basket, and HIPP cells. The GC model consists of an integrate-and-fire somatic compartment connected to a variable numbers of active dendritic compartments. For simplicity reasons, without sacrificing detail, we used point neurons to simulate the remaining neuronal types. GCs major input from the Entorhinal Cortex (EC) is simulated as independent poisson spike trains at realistic firing frequencies. The output of the network corresponds to the spiking activity of GCs and is estimated on two highly overlapping input patterns. Pattern separation is accomplished when the similarity between these input patterns is greater than the similarity between the respective output patterns, as assessed by the Hamming Distance (HD) metric. Preliminary results show that there is a positive correlation between the separation efficiency and the number of GC dendrites. Conclusions: Our preliminary results suggest that dendrites of GC cells facilitate the pattern separation capabilities of the DG.

Heterozygous variants in KCNC2 cause a broad spectrum of epilepsy phenotypes associated with characteristic functional alterations

10.1101/2021.05.21.21257099 ◽

2021 ◽

Author(s):

Niklas Schwarz ◽

Simone Seiffert ◽

Manuela Pendziwiat ◽

Annika Rademacher ◽

Tobias Bruenger ◽

...

Keyword(s):

Functional Analysis ◽

De Novo ◽

Critical Role ◽

Specific Response ◽

Loss Of Function ◽

Causative Gene ◽

Characteristic Functional ◽

Research Collaborations ◽

Background KCNC2 encodes a member of the shaw-related voltage-gated potassium channel family (KV3.2), which are important for sustained high-frequency firing and optimized energy efficiency of action potentials in the brain. Methods Individuals with KCNC2 variants detected by exome sequencing were selected for clinical, further genetic and functional analysis. The cases were referred through clinical and research collaborations in our study. Four de novo variants were examined electrophysiologically in Xenopus laevis oocytes. Results We identified novel KCNC2 variants in 27 patients with various forms of epilepsy. Functional analysis demonstrated gain-of-function in severe and loss-of-function in milder phenotypes as the underlying pathomechanisms with specific response to valproic acid. Conclusion These findings implicate KCNC2 as a novel causative gene for epilepsy emphasizing the critical role of KV3.2 in the regulation of brain excitability with an interesting genotype-phenotype correlation and a potential concept for precision medicine.