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1.
Eur J Med Genet ; 64(5): 104193, 2021 May.
Article in English | MEDLINE | ID: mdl-33746037

ABSTRACT

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder of motile cilia. With few exceptions, PCD is an autosomal recessive condition, and there are over 40 genes associated with the condition. We present a case of a newborn female with clinical features of PCD, specifically the Kartagener syndrome phenotype, due to variants in TTC25. This gene has been previously associated with PCD in three families. Two multi-gene panels performed as a neonate and at two years of age were uninformative. Exome sequencing was performed by the Care4Rare Canada Consortium on a research basis, and an apparent homozygous intronic variant (TTC25:c.1145+1G > A) was identified that was predicted to abolish the canonical splice donor activity of exon 8. The child's mother was a heterozygous carrier of the variant. The paternal sample did not show the splice variant, and homozygosity was observed across the paternal locus. Microarray analysis showed a 50 kb heterozygous deletion spanning the genes TTC25 and CNP. This is the first example of a pathogenic gross deletion in trans with a splice variant, resulting in TTC25-related PCD.


Subject(s)
Carrier Proteins/genetics , Gene Deletion , Kartagener Syndrome/genetics , Carrier Proteins/metabolism , DNA Copy Number Variations , Female , Humans , Infant, Newborn , Kartagener Syndrome/pathology , RNA Splice Sites
2.
Neurogenetics ; 19(1): 61-65, 2018 01.
Article in English | MEDLINE | ID: mdl-29247375

ABSTRACT

Occipital cortical malformation is a rare neurodevelopmental disorder characterized by pachygyria and polymicrogyria of the occipital lobes as well as global developmental delays and seizures. This condition is due to biallelic, loss-of-function mutations in LAMC3 and has been reported in four unrelated families to date. We report an individual with global delays, seizures, and polymicrogyria that extends beyond the occipital lobes and includes the frontal, parietal, temporal, and occipital lobes. Next-generation sequencing identified a homozygous nonsense mutation in LAMC3: c.3190C>T (p.Gln1064*). This finding extends the cortical phenotype associated with LAMC3 mutations.


Subject(s)
Epilepsy/genetics , Laminin/genetics , Polymicrogyria/genetics , Adolescent , Brain/diagnostic imaging , Codon, Nonsense , Epilepsy/complications , Epilepsy/diagnostic imaging , Female , High-Throughput Nucleotide Sequencing , Humans , Polymicrogyria/complications , Polymicrogyria/diagnostic imaging
3.
Clin Genet ; 93(2): 301-309, 2018 02.
Article in English | MEDLINE | ID: mdl-28708278

ABSTRACT

The inherited peripheral neuropathies (IPNs) are characterized by marked clinical and genetic heterogeneity and include relatively frequent presentations such as Charcot-Marie-Tooth disease and hereditary motor neuropathy, as well as more rare conditions where peripheral neuropathy is associated with additional features. There are over 250 genes known to cause IPN-related disorders but it is estimated that in approximately 50% of affected individuals a molecular diagnosis is not achieved. In this study, we examine the diagnostic utility of whole-exome sequencing (WES) in a cohort of 50 families with 1 or more affected individuals with a molecularly undiagnosed IPN with or without additional features. Pathogenic or likely pathogenic variants in genes known to cause IPN were identified in 24% (12/50) of the families. A further 22% (11/50) of families carried sequence variants in IPN genes in which the significance remains unclear. An additional 12% (6/50) of families had variants in novel IPN candidate genes, 3 of which have been published thus far as novel discoveries (KIF1A, TBCK, and MCM3AP). This study highlights the use of WES in the molecular diagnostic approach of highly heterogeneous disorders, such as IPNs, places it in context of other published neuropathy cohorts, while further highlighting associated benefits for discovery.


Subject(s)
Charcot-Marie-Tooth Disease/genetics , Exome Sequencing , High-Throughput Nucleotide Sequencing , Peripheral Nervous System Diseases/genetics , Acetyltransferases/genetics , Charcot-Marie-Tooth Disease/diagnosis , Charcot-Marie-Tooth Disease/pathology , Exome/genetics , Female , Humans , Intracellular Signaling Peptides and Proteins/genetics , Kinesins/genetics , Male , Mutation , Peripheral Nervous System Diseases/diagnosis , Peripheral Nervous System Diseases/pathology , Protein Serine-Threonine Kinases/genetics
4.
Clin Genet ; 92(3): 281-289, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28170084

ABSTRACT

BACKGROUND: Recent clinical whole exome sequencing (WES) cohorts have identified unanticipated multiple genetic diagnoses in single patients. However, the frequency of multiple genetic diagnoses in families is largely unknown. AIMS: We set out to identify the rate of multiple genetic diagnoses in probands and their families referred for analysis in two national research programs in Canada. MATERIALS & METHODS: We retrospectively analyzed WES results for 802 undiagnosed probands referred over the past 5 years in either the FORGE or Care4Rare Canada WES initiatives. RESULTS: Of the 802 probands, 226 (28.2%) were diagnosed based on mutations in known disease genes. Eight (3.5%) had two or more genetic diagnoses explaining their clinical phenotype, a rate in keeping with the large published studies (average 4.3%; 1.4 - 7.2%). Seven of the 8 probands had family members with one or more of the molecularly diagnosed diseases. Consanguinity and multisystem disease appeared to increase the likelihood of multiple genetic diagnoses in a family. CONCLUSION: Our findings highlight the importance of comprehensive clinical phenotyping of family members to ultimately provide accurate genetic counseling.


Subject(s)
Exome Sequencing , Family , Genetic Association Studies , Genetic Diseases, Inborn/diagnosis , Genetic Diseases, Inborn/genetics , Genetic Predisposition to Disease , Canada/epidemiology , Child, Preschool , Consanguinity , Female , Genetic Diseases, Inborn/epidemiology , Genetic Testing , Genotype , Humans , Male , Mutation , Pedigree , Phenotype , Retrospective Studies , Siblings , Exome Sequencing/methods
5.
Clin Genet ; 89(3): 275-84, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26283276

ABSTRACT

An accurate diagnosis is an integral component of patient care for children with rare genetic disease. Recent advances in sequencing, in particular whole-exome sequencing (WES), are identifying the genetic basis of disease for 25-40% of patients. The diagnostic rate is probably influenced by when in the diagnostic process WES is used. The Finding Of Rare Disease GEnes (FORGE) Canada project was a nation-wide effort to identify mutations for childhood-onset disorders using WES. Most children enrolled in the FORGE project were toward the end of the diagnostic odyssey. The two primary outcomes of FORGE were novel gene discovery and the identification of mutations in genes known to cause disease. In the latter instance, WES identified mutations in known disease genes for 105 of 362 families studied (29%), thereby informing the impact of WES in the setting of the diagnostic odyssey. Our analysis of this dataset showed that these known disease genes were not identified prior to WES enrollment for two key reasons: genetic heterogeneity associated with a clinical diagnosis and atypical presentation of known, clinically recognized diseases. What is becoming increasingly clear is that WES will be paradigm altering for patients and families with rare genetic diseases.


Subject(s)
Exome , Genes , Genetic Diseases, Inborn/diagnosis , Mutation , Sequence Analysis, DNA , Canada , Child , Genetic Diseases, Inborn/genetics , High-Throughput Nucleotide Sequencing , Humans
6.
Clin Genet ; 88(1): 34-40, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25046240

ABSTRACT

Whole-exome sequencing (WES) has transformed our ability to detect mutations causing rare diseases. FORGE (Finding Of Rare disease GEnes) and Care4Rare Canada are nation-wide projects focused on identifying disease genes using WES and translating this technology to patient care. Rare forms of epilepsy are well-suited for WES and we retrospectively selected FORGE and Care4Rare families with clinical descriptions that included childhood-onset epilepsy or seizures not part of a recognizable syndrome or an early-onset encephalopathy where standard-of-care investigations were unrevealing. Nine families met these criteria and a diagnosis was made in seven, and potentially eight, of the families. In the eight families we identified mutations in genes associated with known neurological and epilepsy disorders: ASAH1, FOLR1, GRIN2A (two families), SCN8A, SYNGAP1 and SYNJ1. A novel and rare mutation was identified in KCNQ2 and was likely responsible for the benign seizures segregating in the family though additional evidence would be required to be definitive. In retrospect, the clinical presentation of four of the patients was considered atypical, thereby broadening the phenotypic spectrum of these conditions. Given the extensive clinical and genetic heterogeneity associated with epilepsy, our findings suggest that WES may be considered when a specific gene is not immediately suspected as causal.


Subject(s)
Epilepsy/genetics , Genetic Predisposition to Disease , Mutation , Adolescent , Adult , Brain Diseases/genetics , Child , Child, Preschool , DNA Mutational Analysis , Exome , Female , Humans , Infant , Infant, Newborn , Male , Pedigree , Phenotype , Retrospective Studies
7.
Radiat Prot Dosimetry ; 167(4): 552-61, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25433049

ABSTRACT

This paper describes modelling, application and validation of a filtration technique for a linear slot-scanning digital X-ray system to reduce radiation dose to paediatric patients while preserving diagnostic image quality. A dose prediction model was implemented, which calculates patient entrance doses using variable input parameters. Effective dose is calculated using a Monte Carlo simulation. An added filter of 1.8-mm aluminium was predicted to lower the radiation dose significantly. An objective image quality study was conducted using detective quantum efficiency (DQE). The PTW Normi 4FLU test phantom was used for quantitative assessment, showing that image contrast and spatial resolution were maintained with the proposed filter. A paediatric cadaver full-body imaging trial assessed the diagnostic quality of the images and measured the dose reduction using a 1.8-mm aluminium filter. Assessment by radiologists indicated that diagnostic quality was maintained with the added filtration, despite a reduction in DQE. A new filtration technique for full-body paediatric scanning on the Lodox Statscan has been validated, reducing entrance dose for paediatric patients by 36 % on average and effective dose by 27 % on average, while maintaining image quality.


Subject(s)
Filtration/instrumentation , Phantoms, Imaging , Radiation Injuries/prevention & control , Radiographic Image Enhancement/instrumentation , Whole Body Imaging/instrumentation , Aluminum/chemistry , Cadaver , Female , Humans , Infant , Infant, Newborn , Male , Monte Carlo Method , Radiation Dosage , Whole-Body Counting , X-Rays
8.
Article in English | MEDLINE | ID: mdl-24110192

ABSTRACT

This paper examines the effect that a 1.8 mm aluminium filter has on paediatric patient dose and image quality for linear slot scanning radiography (LSSR). A dynamic dose prediction model for LSSR accurately predicted the dose reduction effects of added aluminium filtration. A cadaver imaging study was carried out to assess the effects of filtration on image quality. With 1.8 mm added aluminium filtration, no visible degradation to image contrast or clarity was found, and in some cases the aluminium filtration improved the image quality as judged by radiologists.


Subject(s)
Aluminum/chemistry , Radiographic Image Enhancement/methods , Filtration , Humans , Infant , Infant, Newborn , Phantoms, Imaging , Radiation Dosage , Radiation Injuries/prevention & control
9.
Philos Trans A Math Phys Eng Sci ; 371(1990): 20120151, 2013 May 13.
Article in English | MEDLINE | ID: mdl-23547228

ABSTRACT

A new and simplified method for the solution of linear constant coefficient fractional differential equations of any commensurate order is presented. The solutions are based on the R-function and on specialized Laplace transform pairs derived from the principal fractional meta-trigonometric functions. The new method simplifies the solution of such fractional differential equations and presents the solutions in the form of real functions as opposed to fractional complex exponential functions, and thus is directly applicable to real-world physics.

10.
Indian J Clin Biochem ; 25(1): 92-8, 2010 Jan.
Article in English | MEDLINE | ID: mdl-23105892

ABSTRACT

The aim of this study was to design an audit questionnaire that focuses on the management of the technical activities in a Diagnostic Pathology Laboratory. The ISO 15189 Standard is written in such a way that it continually moves back and forth from topics where the auditor needs to question bench level staff, to topics where the auditor needs to question Technical Management Staff. This makes for a disjointed audit process - both Bench Staff and Technical Managers are repeatedly interrupted. The solution was to do a clause by clause analysis of the Standard and assign the major responsibility for the compliance to each clause to either Technical Managers or Bench Staff. The Clauses were then grouped under four topic headings regardless of whether they were a Section 4 or Section 5 Clause. Two questionnaires have emerged - the one described in this work and one directed primarily towards the activities of bench staff. There are 95 questions and it takes approximately two hours to complete.

11.
Undersea Hyperb Med ; 34(5): 341-8, 2007.
Article in English | MEDLINE | ID: mdl-18019085

ABSTRACT

The main technological problem associated with measuring gas exchange in submerged divers breathing from a self-contained underwater breathing apparatus (SCUBA) involves simulating ambient water pressure on the expired side of the SCUBA regulator without causing regulator free-flow. This report presents a method to acquire expired gas from exercising divers for analysis at the surface using a standard metabolic measurement system. We did this using a flat collapsible tube downstream from the expiration valve of the regulator. We tested 12 divers while swimming on the surface and during SCUBA at 1.8 m (6 ft) underwater using a tethered swim/counter weight system to provide graded exercise to exhaustion. Peak minute ventilation was not significantly different between surface swimming and SCUBA, but peak oxygen consumption (VO2) was lower (p < 0.0001) during SCUBA than for surface swimming. There was a significant correlation (p = 0.0002) between peak VO2 during SCUBA and surface swimming. These results show that VO2 and ventilation can be accurately measured in SCUBA divers during underwater exercise and the new and simple technique will be useful to those interested in the energy requirements of diving activities in shallow water.


Subject(s)
Breath Tests/methods , Diving/physiology , Oxygen Consumption/physiology , Adult , Breath Tests/instrumentation , Equipment Design , Humans , Male , Swimming/physiology
12.
Neuroimage ; 28(1): 256-67, 2005 Oct 15.
Article in English | MEDLINE | ID: mdl-16027012

ABSTRACT

Different patterns of prefrontal activation are commonly found in studies of episodic and source memory (typically anterior and lateral) compared to those found in studies of autobiographical memory (typically ventromedial). We investigated a proposal that the former pattern reflects contextual interference when retrieving events that occurred in similar contexts. We used virtual reality to simulate contextually varied life-like events, in which subjects received distinct objects from a number of people in a number of locations. We compared fMRI data from two experiments in which the number of events per context varied. The first experiment (Burgess, N., Maguire, E.A., Spiers, H.J., and O'Keefe, J. 2001. A temporoparietal and prefrontal network for retrieving the spatial context of lifelike events. Neuroimage 14, 439-453) involved 16 objects received from one of two people in one of two locations. The second experiment involved 20 objects, each received from a different person in a different location. The first experiment showed extensive bilateral activation of anterior and lateral prefrontal cortex, as well as a medial temporal and parietal network characteristic of both autobiographical and episodic memory. In the second study, the prefrontal activations were largely absent, while the medial parietal and temporal activations remained, and a ventromedial prefrontal area was additionally activated. Direct comparisons revealed large areas of significantly reduced activation in BA10, with lesser reductions in lateral prefrontal regions. We suggest that involvement of these prefrontal regains in episodic and source memory reflects the use of paradigms involving many events and few sources rather than any fundamental processing requirement of contextual retrieval in the absence of interference.


Subject(s)
Memory/physiology , Prefrontal Cortex/physiology , Adolescent , Adult , Contrast Sensitivity , Cues , Data Interpretation, Statistical , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Middle Aged , Models, Neurological
13.
J Appl Physiol (1985) ; 95(2): 591-601, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12716872

ABSTRACT

Orthostatic reflexes were examined at 375 m and after 60 min of exposure in a hypobaric chamber at 3660 m using a 20-min 70 degrees head-up tilt (HUT) test. Mean arterial blood pressure, R wave-R wave interval (RRI), and mean cerebral blood flow velocity (MFV) were examined with coarse-graining spectral analysis. Of 14 subjects, 7 at 375 m and 12 at 3660 m were presyncopal. Immediately on arrival to high altitude, breathing frequency and MFV increased, and endtidal PCO2, RRI, RRI complexity, and the parasympathetic nervous system indicator decreased. MFV was similar in HUT at both altitudes. The sympathetic nervous system indicator increased with tilt at 3660 m, whereas parasympathetic nervous system indicator decreased with tilt at both altitudes. Multiple regression analysis of supine variables from either 375 or 3660 m and the time to presyncope at 3660 m indicated that, after 1 h of exposure, increased presyncope at altitude was the result of 1). ineffective peripheral vasoconstriction, despite increased cardiac sympathetic nervous system activity with HUT, and 2). insufficient cerebral perfusion owing to cerebral vasoconstriction as the result of hypoxic hyperventilation-induced hypocapnia.


Subject(s)
Adaptation, Physiological , Altitude , Hypotension, Orthostatic/etiology , Hypotension, Orthostatic/physiopathology , Adult , Baroreflex , Blood Flow Velocity , Blood Pressure , Cerebrovascular Circulation , Female , Heart Rate , Humans , Hyperventilation/etiology , Hyperventilation/physiopathology , Incidence , Male , Respiration , Syncope/epidemiology , Syncope/physiopathology , Tilt-Table Test
14.
J Clin Hypertens (Greenwich) ; 3(6): 354-61, 2001.
Article in English | MEDLINE | ID: mdl-11723357

ABSTRACT

Caffeine use is widespread, and its consumption increases during periods of stress. Caffeine raises blood pressure by elevating vascular resistance, and this effect is larger and more prolonged in hypertensive patients than in normotensive. The pressor response to caffeine occurs equally in persons at rest and under stress. The elevated baseline pressures of the hypertensive patient are therefore increased by both caffeine and stress, potentially leading to undesirably high pressures. Such combined effects on blood pressure may potentially confound the evaluation of hypertension, and possibly reduce the effectiveness of antihypertensive therapy. These effects are not abolished by pharmacologic tolerance to caffeine, as tolerance may not be complete with daily intake. The contribution of caffeine's effects to the development of hypertension warrants continued study, and caffeine use by patients merits consideration in terms of assessment and management of this disorder.


Subject(s)
Caffeine/pharmacology , Stress, Physiological , Blood Pressure/drug effects , Blood Pressure/physiology , Feeding Behavior , Humans , Hypertension/physiopathology , Hypertension/therapy , Life Style , Risk Factors , United States/epidemiology
15.
Brain ; 124(Pt 12): 2476-89, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11701601

ABSTRACT

A large-scale virtual reality town was used to test the topographical and episodic memory of patients with unilateral temporal lobe damage. Seventeen right and 13 left temporal lobectomy patients were compared with 16 healthy matched control subjects. After they had explored the town, subjects' topographical memory was tested by requiring them to navigate to specific locations in the town. The ability to recognize scenes from and draw maps of the virtual town was also assessed. Following the topographical memory tests, subjects followed a route around the same town but now collected objects from two different characters in two different locations. Episodic memory for various aspects of these events was then assessed by paired forced-choice recognition tests. The results showed an interaction between laterality and test type such that the right temporal lobectomy (RTL) patients were worse on tests of topographical memory, and the left temporal lobectomy (LTL) patients worse on tests of context-dependent episodic memory. Specifically, the RTL group was impaired on navigation, scene recognition and map drawing relative to control subjects. They were also impaired on recognition of objects in the episodic memory task. The LTL group was impaired relative to control subjects on their memory for contextual aspects of the events, such as who gave them the objects, the order in which objects were received and the locations in which they received them. They were also mildly impaired on topographical memory, but less so than the RTL group. These results suggest that topographical memory is predominately mediated by structures in the right medial temporal lobe, whereas the context-dependent aspects of episodic memory in this non-verbal test are more dependent on the left medial temporal lobe.


Subject(s)
Epilepsy/physiopathology , Epilepsy/surgery , Memory Disorders/physiopathology , Temporal Lobe/physiopathology , Temporal Lobe/surgery , Adult , Female , Functional Laterality , Humans , Male , Memory Disorders/etiology , Recognition, Psychology , Space Perception , User-Computer Interface
16.
Perception ; 30(1): 61-72, 2001.
Article in English | MEDLINE | ID: mdl-11257978

ABSTRACT

Detection of coherent motion versus noise is widely used as a measure of global visual-motion processing. To localise the human brain mechanisms involved in this performance, functional magnetic resonance imaging (fMRI) was used to compare brain activation during viewing of coherently moving random dots with that during viewing spatially and temporally comparable dynamic noise. Rates of reversal of coherent motion and coherent-motion velocities (5 versus 20 deg s-1) were also compared. Differences in local activation between conditions were analysed by statistical parametric mapping. Greater activation by coherent motion compared to noise was found in V5 and putative V3A, but not in V1. In addition there were foci of activation on the occipital ventral surface, the intraparietal sulcus, and superior temporal sulcus. Thus, coherent-motion information has distinctive effects in a number of extrastriate visual brain areas. The rate of motion reversal showed only weak effects in motion-sensitive areas. V1 was better activated by noise than by coherent motion, possibly reflecting activation of neurons with a wider range of motion selectivities. This activation was at a more anterior location in the comparison of noise with the faster velocity, suggesting that 20 deg s-1 is beyond the velocity range of the V1 representation of central visual field. These results support the use of motion-coherence tests for extrastriate as opposed to V1 function. However, sensitivity to motion coherence is not confined to V5, and may extend beyond the classically defined dorsal stream.


Subject(s)
Brain Mapping , Brain/physiology , Magnetic Resonance Imaging , Motion Perception/physiology , Brain/anatomy & histology , Computer Graphics , Humans , Psychophysics
18.
Hippocampus ; 11(6): 715-25, 2001.
Article in English | MEDLINE | ID: mdl-11811666

ABSTRACT

A virtual reality environment was used to test memory performance for simulated "real-world" spatial and episodic information in a 22-year-old male, Jon, who has selective bilateral hippocampal pathology caused by perinatal anoxia. He was allowed to explore a large-scale virtual reality town and was then tested on his memory for spatial layout and for episodes experienced. Topographical memory was tested by assessing his ability to navigate, recognize previously visited locations, and draw maps of the town. Episodic memory was assessed by testing the retrieval of simulated events which consisted of collecting objects from characters while following a route through the virtual town. Memory for the identity of objects, as well as for where they were collected, from whom, and in what order, was also tested. While the first task tapped simple recognition memory, the latter three tested memory for context. Jon was impaired on all topographical tasks and on his recall of the context-dependent questions. However, his recognition of objects from the virtual town, and of "topographical" scenes (as evaluated by standard neuropsychological tests), was not impaired. These findings are consistent with the view that the hippocampus is involved in navigation, recall of long term allocentric spatial information and context-dependent episodic memory, but not visual pattern matching.


Subject(s)
Brain Diseases/physiopathology , Brain Diseases/psychology , Dominance, Cerebral , Hippocampus/physiopathology , Memory/physiology , Pattern Recognition, Visual/physiology , Adult , Child , Discrimination, Psychological/physiology , Humans , Male , Mental Recall/physiology , Neuropsychological Tests , Recognition, Psychology/physiology , Space Perception/physiology , User-Computer Interface
19.
Hippocampus ; 10(4): 369-79, 2000.
Article in English | MEDLINE | ID: mdl-10985276

ABSTRACT

A model of place-cell firing is presented that makes quantitative predictions about specific place cells' spatial receptive fields following changes to the rat's environment. A place cell's firing rate is modeled as a function of the rat's location by the thresholded sum of the firing rates of a number of putative cortical inputs. These inputs are tuned to respond whenever an environmental boundary is at a particular distance and allocentric direction from the rat. The initial behavior of a place cell in any environment is simply determined by its set of inputs and its threshold; learning is not necessary. The model is shown to produce a good fit to the firing of individual place cells, and populations of place cells across environments of differing shape. The cells' behavior can be predicted for novel environments of arbitrary size and shape, or for manipulations such as introducing a barrier. The model can be extended to make behavioral predictions regarding spatial memory.


Subject(s)
Cerebral Cortex/physiology , Hippocampus/physiology , Models, Neurological , Space Perception/physiology , Afferent Pathways/physiology , Animals
20.
Biol Cybern ; 83(3): 301-12, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11007303

ABSTRACT

A computational model of the lesion and single unit data from navigation in rats is reviewed. The model uses external (visual) and internal (odometric) information from the environment to drive the firing of simulated hippocampal place cells. Constraints on the functional form of these inputs are drawn from experiments using an environment of modifiable shape. The place cell representation is used to guide navigation via the creation of a representation of goal location via Hebbian modification of synaptic strengths. The model includes consideration of the phase of firing of place cells with respect to the theta rhythm of hippocampal EEG. A series of predictions for behavioural and single-unit data in rats are derived from the input and output representations of the model.


Subject(s)
Behavior, Animal , Hippocampus , Models, Biological , Models, Theoretical , Neurons , Psychomotor Performance , Animals , Rats
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