68 research outputs found
Visual experience induces long-term potentiation in the primary visual
Full text linkStimulus-specific response potentiation (SRP) is a robust form of experience-dependent plasticity that occurs in primary visual cortex. In awake mice, visual evoked potentials (VEPs) recorded in layer 4 of binocular visual cortex undergo increases in amplitude with repeated presentation of a sinusoidal grating stimulus over days. This effect is highly specific to the experienced stimulus. Here, we test whether the mechanisms of thalamocortical long-term potentiation (LTP), induced with a theta burst electrical stimulation (TBS) of the dorsal lateral geniculate nucleus, are sufficient to account for SRP. First, we demonstrate that LTP similarly enhances the amplitude of VEPs, but in a way that generalizes across multiple stimuli, spatial frequencies, and contrasts. Second, we show that LTP occludes the subsequent expression of SRP. Third, we reveal that previous SRP occludes TBS-induced LTP of the VEP evoked by the experienced stimulus, but not by unfamiliar stimuli. Finally, we show that SRP is rapidly and selectively reversed by local cortical infusion of a peptide that inhibits PKMζ, a constitutively active kinase known to maintain NMDA receptor-dependent LTP and memory. Thus, SRP is expressed by the same core mechanisms as LTP. SRP therefore provides a simple assay to assess the integrity of LTP in the intact nervous system. Moreover, the results suggest that LTP of visual cortex, like SRP, can potentially be exploited to improve vision.National Eye Institute (Grant R01 EY018323-01
Visual recognition memory: a view from V1
Full text linkAlthough work in primates on higher-order visual areas has revealed how the individual and concerted activity of neurons correlates with behavioral reports of object recognition, very little is known about the underlying mechanisms for visual recognition memory. Low-level vision, even as early as primary visual cortex (V1) and even in subjects as unsophisticated as rodents, promises to fill this void. Although this latter approach sacrifices interrogation of many of the most astounding features of visual recognition, it does provide experimental constraint, proximity to sensory input, and a wide range of interventional approaches. The tractability of rodent visual cortex promises to reveal the molecular mechanisms and circuits that are essential for a fundamental form of memory.National Eye Institute (Grant RO1EY023037
Experience-Dependent Equilibration of AMPAR-Mediated Synaptic Transmission during the Critical Period
Full text linkExperience-dependent synapse refinement is essential for functional optimization of neural circuits. However, how sensory experience sculpts excitatory synaptic transmission is poorly understood. Here, we show that despite substantial remodeling of synaptic connectivity, AMPAR-mediated synaptic transmission remains at equilibrium during the critical period in the mouse primary visual cortex. The maintenance of this equilibrium requires neurogranin (Ng), a postsynaptic calmodulin-binding protein important for synaptic plasticity. With normal visual experience, loss of Ng decreased AMPAR-positive synapse numbers, prevented AMPAR-silent synapse maturation, and increased spine elimination. Importantly, visual deprivation halted synapse loss caused by loss of Ng, revealing that Ng coordinates experience-dependent AMPAR-silent synapse conversion to AMPAR-active synapses and synapse elimination. Loss of Ng also led to sensitized long-term synaptic depression (LTD) and impaired visually guided behavior. Our synaptic interrogation reveals that experience-dependent coordination of AMPAR-silent synapse conversion and synapse elimination hinges upon Ng-dependent mechanisms for constructive synaptic refinement during the critical period.JPB FoundationWhitehall FoundationStanley Center for Psychiatric Research at Broad Institut
Visual recognition memory, manifested as long-term habituation, requires synaptic plasticity in V1
No full textFamiliarity with stimuli that bring neither reward nor punishment, manifested through behavioral habituation, enables organisms to detect novelty and devote cognition to important elements of the environment. Here we describe in mice a form of long-term behavioral habituation to visual grating stimuli that is selective for stimulus orientation. Orientation-selective habituation (OSH) can be observed both in exploratory behavior in an open arena and in a stereotyped motor response to visual stimuli in head-restrained mice. We found that the latter behavioral response, termed a 'vidget', requires V1. Parallel electrophysiological recordings in V1 revealed that plasticity, in the form of stimulus-selective response potentiation (SRP), occurred in layer 4 of V1 as OSH developed. Local manipulations of V1 that prevented and reversed electrophysiological modifications likewise prevented and reversed memory demonstrated behaviorally. These findings suggest that a form of long-term visual recognition memory is stored via synaptic plasticity in primary sensory cortex.Howard Hughes Medical InstituteNational Eye Institute (Grant RO1EY023037)Picower Institute for Learning and Memory (Innovation Fund)Picower Institute for Learning and Memory (Neurological Disorder Research Fund)JPB Foundation (Fellowship)National Institute of Mental Health (U.S.) (Training Grant 5T32MH074249)National Institute of Mental Health (U.S.) (Grant K99MH099654
The tort/contract boundary: great divide or grand illusion
Full text linkThis thesis considers the difference between contract and the tort of negligence. It compares the traditional view of the distinction with a more contemporary view, and concludes that the two areas of law are becoming interrelated. Three main aspects of contract and tort are compared; the nature of the liability, the scope of the liability and the extent of the remedy. The historical origins of the two areas of law are explored, as are the ideological concepts which underpin them. There is also an investigation of how the courts in the UK deal with the relationship between contract and tort in both contracts for services and contracts of service; these being two areas where there is a considerable overlap between contractual and tortious liability. The thesis argues that contract and the tort of negligence are based on common historical roots and underpinned by common ideologies. In both cases, the courts seek to decide liability on the basis of 'reasonableness', a subjective concept which is determined according to their own criteria. This is seen as related to such factors as the bargaining power of the litigants, and their opportunities to secure alternative means of protection against liability. It is suggested that this is more important than whether the action is brought in contract or tort. The nature of the contract/tort divide is considered in the alternative jurisdiction of New Zealand, in order to see how it deals with the problems posed. The thesis concludes by considering whether an alternative model could be constructed in order to explain the current nature of the relationship between contract and tort, and what type of relationship should exist
Contrasting roles for parvalbumin-expressing inhibitory neurons in two forms of adult visual cortical plasticity
Full text linkThe roles played by cortical inhibitory neurons in experience-dependent plasticity are not well understood. Here we evaluate the participation of parvalbumin-expressing (PV+) GABAergic neurons in two forms of experience-dependent modification of primary visual cortex (V1) in adult mice: ocular dominance (OD) plasticity resulting from monocular deprivation and stimulus-selective response potentiation (SRP) resulting from enriched visual experience. These two forms of plasticity are triggered by different events but lead to a similar increase in visual cortical response. Both also require the NMDA class of glutamate receptor (NMDAR). However, we find that PV+ inhibitory neurons in V1 play a critical role in the expression of SRP and its behavioral correlate of familiarity recognition, but not in the expression of OD plasticity. Furthermore, NMDARs expressed within PV+ cells, reversibly inhibited by the psychotomimetic drug ketamine, play a critical role in SRP, but not in the induction or expression of adult OD plasticity.Howard Hughes Medical InstituteNational Eye Institute (5R01EYO23037)Picower Institute for Learning and Memory (Innovation Fund)National Institute of Mental Health (U.S.) (Training Grant 1T32MH074249)JPB Foundation. Junior Facutly Development Progra
Plasticity in the human central nervous system.
No full textLong-term potentiation (LTP) is a well-characterized form of synaptic plasticity that fulfils many of the criteria for a neural correlate of memory. LTP has been studied in a variety of animal models and, in rodents in particular, there is now a strong body of evidence demonstrating common underlying molecular mechanisms in LTP and memory. Results are beginning to emerge from studies of neural plasticity in humans. This review will summarize findings demonstrating that synaptic LTP can be induced in human CNS tissue and that rodent and human LTP probably share similar molecular mechanisms. We will also discuss the application of non-invasive stimulation techniques to awake human subjects to induce LTP-like long-lasting changes in localized neural activity. These techniques have potential therapeutic application in manipulating neural plasticity to treat a variety of conditions, including depression, Parkinson's disease, epilepsy and neuropathic pain
Stimulus-Selective Response Plasticity in the Visual Cortex: An Assay for the Assessment of Pathophysiology and Treatment of Cognitive Impairment Associated with Psychiatric Disorders
No full textLong-term potentiation (LTP) is a form of experimentally induced enhancement of chemical synaptic transmission that has long been proposed as a model of the endogenous processes of synaptic plasticity that mediate memory. There is a large body of evidence that the molecular mechanisms underlying experimentally induced LTP also subserve various forms of naturally occurring, experience-dependent synaptic plasticity in animals and humans. Here we describe a phenomenon called stimulus-specific response potentiation (SRP), which occurs in the primary visual cortex of mice as a result of repeated exposure to visual stimuli and is believed to reveal the mechanisms that underlie perceptual learning. We first describe evidence that SRP represents naturally occurring LTP of thalamo-cortical synaptic transmission. We then discuss the potential value of SRP as a preclinical assay for the assessment of putative drug treatments on synaptic plasticity. Stimulus-specific response potentiation is not only easy to assay and robust but captures features of feed-forward glutamatergic function and visual learning that are deficient in human psychiatric disorders, notably including schizophrenia. We suggest that phenomena analogous to SRP in humans are likely to be useful biomarkers of altered cortical LTP and of treatment response in diseases associated with impaired cognition
Synaptic plasticity, memory and the hippocampus: a neural network approach to causality
No full textTwo facts about the hippocampus have been common currency among neuroscientists for several decades. First, lesions of the hippocampus in humans prevent the acquisition of new episodic memories; second, activity-dependent synaptic plasticity is a prominent feature of hippocampal synapses. Given this background, the hypothesis that hippocampus-dependent memory is mediated, at least in part, by hippocampal synaptic plasticity has seemed as cogent in theory as it has been difficult to prove in practice. Here we argue that the recent development of transgenic molecular devices will encourage a shift from mechanistic investigations of synaptic plasticity in single neurons towards an analysis of how networks of neurons encode and represent memory, and we suggest ways in which this might be achieved. In the process, the hypothesis that synaptic plasticity is necessary and sufficient for information storage in the brain may finally be validated
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Rural life in English poetry of the mid-eighteenth century
Full text linkThis thesis examines several mid-eighteenth century poems, assessing their portrayal of rural life, its literary and historical significance, and the aesthetic and ideological issues it presents. An introductory essay on developments in rural poetry sets the scene for two extended essays. The first essay is a comparative reading of the subject of rural labour in three poems: James Thomson’s The Seasons (1726-44), Stephen Duck’s The Thresher’s Labour (1730, 1736) and Mary Collier’s The Woman’s Labour (1739). The viewpoints of a professional poet (Thomson), a farm labourer (Duck), and a working woman (Collier) are compared in relation to kinds of work all three address as well as to individual labouring subjects. The responses of the three poets to such related issues as folk traditions, forms of charity and other ‘compensations’, are also compared. Some surprising similarities as well as instructive differences are located; and an interesting picture of idealistic and realistic, male-oriented and female-oriented attitudes to labour and labour-related themes emerges
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