scholarly journals Excitatory postsynaptic calcium transients at Aplysia sensory–motor neuron synapses allow for quantal examination of synaptic strength over multiple days in culture

2021 ◽  
Vol 28 (9) ◽  
pp. 277-290
Author(s):  
Tyler W. Dunn ◽  
Wayne S. Sossin
Keyword(s):  
Motor Neuron ◽  
Release Site ◽  
Synaptic Strength ◽  
Synaptic Contacts ◽  
Homosynaptic Depression ◽  
Quantal Size ◽  
Synaptic Changes ◽  
The Individual ◽  
Postsynaptic Calcium

A more thorough description of the changes in synaptic strength underlying synaptic plasticity may be achieved with quantal resolution measurements at individual synaptic sites. Here, we demonstrate that by using a membrane targeted genetic calcium sensor, we can measure quantal synaptic events at the individual synaptic sites of Aplysia sensory neuron to motor neuron synaptic connections. These results show that synaptic strength is not evenly distributed between all contacts in these cultures, but dominated by multiquantal sites of synaptic contact, likely clusters of individual synaptic sites. Surprisingly, most synaptic contacts were not found opposite presynaptic varicosities, but instead at areas of pre- and postsynaptic contact with no visible thickening of membranes. The release probability, quantal size, and quantal content can be measured over days at individual synaptic contacts using this technique. Homosynaptic depression was accompanied by a reduction in release site probability, with no evidence of individual synaptic site silencing over the course of depression. This technique shows promise in being able to address outstanding questions in this system, including determining the synaptic changes that maintain long-term alterations in synaptic strength that underlie memory.

scholarly journals Excitatory postsynaptic calcium transients at Aplysia sensory-motor neuron synapses allow for quantal examination of synaptic strength over multiple days in culture

2021 ◽  
Author(s):  
Tyler W Dunn ◽  
Wayne S Sossin
Keyword(s):  
Motor Neuron ◽  
Ampa Receptors ◽  
Synaptic Contact ◽  
Synaptic Strength ◽  
Calcium Transients ◽  
Calcium Sensor ◽  
Synaptic Contacts ◽  
Quantal Size ◽  
Sensory Motor ◽  
Postsynaptic Calcium

AbstractThe ability to monitor changes in strength at individual synaptic contacts is required to test the hypothesis that specialized synapses maintain changes in synaptic strength that underlie memory. Measuring excitatory post-synaptic calcium transients through calcium permeable AMPA receptors is one way to monitor synaptic strength at individual synaptic contacts. Using a membrane targeted genetic calcium sensor, we demonstrate that one can measure synaptic events at individual synaptic contacts in Aplysia sensory-motor neuron synapses. These results show that synaptic strength is not evenly distributed between all contacts in these cultures, but dominated by multiquantal sites of synaptic contact. The probability, quantal size and quantal content can be measured over days at individual synaptic contacts using this technique. Surprisingly, most synaptic contacts were not found opposite presynaptic varicosities, but instead at areas of pre- and post-synaptic contact with no visible thickening of membranes. This technique shows promise in being able to address whether specialized synapses maintain synaptic strength underlying memory.

A Statistical Theory of Long-Term Potentiation and Depression

2001 ◽  
Vol 13 (1) ◽  
pp. 87-111 ◽  
Author(s):  
John M. Beggs
Keyword(s):  
Response Curve ◽  
Long Term Potentiation ◽  
Synaptic Strength ◽  
Excitatory Synapses ◽  
Field Potentials ◽  
Postsynaptic Activity ◽  
Term Potentiation ◽  
Synaptic Changes ◽  
Cortical Slices

The synaptic phenomena of long-term potentiation (LTP) and long-term depression (LTD) have been intensively studied for over twenty-five years. Although many diverse aspects of these forms of plasticity have been observed, no single theory has offered a unifying explanation for them. Here, a statistical “bin” model is proposed to account for a variety of features observed in LTP and LTD experiments performed with field potentials in mammalian cortical slices. It is hypothesized that long-term synaptic changes will be induced when statistically unlikely conjunctions of pre- and postsynaptic activity occur. This hypothesis implies that finite changes in synaptic strength will be proportional to information transmitted by conjunctions and that excitatory synapses will obey a Hebbian rule (Hebb, 1949). Using only one set of constants, the bin model offers an explanation as to why synaptic strength decreases in a decelerating manner during LTD induction (Mulkey & Malenka, 1992); why the induction protocols for LTP and LTD are asymmetric (Dudek & Bear, 1992; Mulkey & Malenka, 1992); why stimulation over a range of frequencies produces a frequency-response curve similar to that proposed by the BCM theory (Bienenstock, Cooper, & Munro, 1982; Dudek & Bear, 1992); and why this curve would shift as postsynaptic activity is changed (Kirkwood, Rioult, & Bear, 1996). In addition, the bin model offers an alternative to the BCM theory by predicting that changes in postsynaptic activity will produce vertical shifts in the curve rather than merely horizontal shifts.

scholarly journals Isoform specificity of PKMs during long-term facilitation in Aplysia is mediated through stabilization by KIBRA

2019 ◽  
Author(s):  
Larissa Ferguson ◽  
Jiangyuan Hu ◽  
Diancai Cai ◽  
Shanping Chen ◽  
Tyler W Dunn ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Motor Neuron ◽  
Sensory Neuron ◽  
Adaptor Protein ◽  
Alpha Helix ◽  
Synaptic Strength ◽  
Dominant Negative ◽  
Isoform Specificity ◽  
Long Term Facilitation

AbstractPersistent activity of protein kinase M (PKM), the truncated form of protein kinase C (PKC), can maintain long-term changes in synaptic strength in many systems including the hermaphrodite marine mollusk, Aplysia californica. Moreover, different types of long-term facilitation (LTF) in cultured Aplysia sensorimotor synapses rely on the activities of different PKM isoforms in the presynaptic sensory neuron and postsynaptic motor neuron. When the atypical PKM isoform was required, the kidney and brain expressed adaptor protein (KIBRA) was also required. Here, we explore how this isoform specificity is established. We find that PKM overexpression in the motor neuron, but not the sensory neuron, is sufficient to increase synaptic strength and that this activity is not isoform specific. KIBRA is not the rate-limiting step in facilitation since overexpression of KIBRA is neither sufficient to increase synaptic strength, nor to prolong a form of PKM-dependent intermediate synaptic facilitation. However, the isoform specificity of dominant negative (DN)-PKMs to erase LTF is correlated with isoform specific competition for stabilization by KIBRA. We identify a new conserved region of KIBRA. Different splice isoforms in this region stabilize different PKMs based on the isoform-specific sequence of an alpha-helix ‘handle’ in the PKMs. Thus, specific stabilization of distinct PKMs by different isoforms of KIBRA can explain the isoform specificity of PKMs during LTF in Aplysia.Significance StatementLong lasting changes in synaptic plasticity associated with memory formation are maintained by persistent protein kinases. We have previously shown in the Aplysia sensorimotor model that distinct isoforms of persistently active protein kinase Cs (PKMs) maintain distinct forms of long-lasting synaptic changes, even when both forms are expressed in the same motor neuron. Here, we show that, while the effects of overexpression of PKMs in not isoform specific, isoform specificity is defined by a ‘handle’ helix in PKMs that confers stabilization by distinct splice forms in a previously undefined domain of the adaptor protein KIBRA. Thus, we define new regions in both KIBRA and PKMs that define the isoform specificity for maintaining synaptic strength in distinct facilitation paradigms.

The Acceptance of Party Unity in Parliamentary Democracies

2017 ◽  
Author(s):  
David M. Willumsen
Keyword(s):  
Political Parties ◽  
Costs And Benefits ◽  
Parliamentary Democracies ◽  
Survey Questions ◽  
Ideal Policy ◽  
Central Argument ◽  
The Individual ◽  
Policy Incentives

The central argument of this book is that voting unity in European legislatures is not primarily the result of the ‘disciplining’ power of the leadership of parliamentary parties, but rather the result of a combination of ideological homogeneity through self-selection into political parties and the calculations of individual legislators about their own long-term benefits. Despite the central role of policy preferences in the subsequent behaviour of legislators, preferences at the level of the individual legislator have been almost entirely neglected in the study of parliaments and legislative behaviour. The book measures these using an until now under-utilized resource: parliamentary surveys. Building on these, the book develops measures of policy incentives of legislators to dissent from their parliamentary parties, and show that preference similarity amongst legislators explains a very substantial proportion of party unity, yet alone cannot explain all of it. Analysing the attitudes of legislators to the demands of party unity, and what drives these attitudes, the book argues that what explains the observed unity (beyond what preference similarity would explain) is the conscious acceptance by MPs that the long-term benefits of belonging to a united party (such as increased influence on legislation, lower transaction costs, and better chances of gaining office) outweigh the short-terms benefits of always voting for their ideal policy outcome. The book buttresses this argument through the analysis of both open-ended survey questions as well as survey questions on the costs and benefits of belonging to a political party in a legislature.

scholarly journals Title I: Modernizing Definitions and Programs Under the Administration on Aging

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 714-715
Author(s):  
Marie Gualtieri
Keyword(s):  
Title I ◽  
Adult Population ◽  
Term Care ◽  
Older Americans ◽  
Aging Society ◽  
Program Adaptation ◽  
Older Americans Act ◽  
The Individual ◽  
Older Adult Population

Abstract The recent reauthorization of the Older Americans Act adds language and definitions to current issues facing the aging population. Specifically, Title I includes definitions related to program adaptation and coordination, workforce and long-term care issues, nutrition and social isolation, as well as family caregivers. Different from the last authorization, these definitions span beyond the individual experience to include other entities impacted by an aging society, such as the workforce and families. Overall, the Title I reauthorization seeks to modernize policy to reflect the current influx of the older adult population and its consequences.

scholarly journals Housing adaptations and housing accessibility problems among older adults with long-standing spinal cord injury

2020 ◽  
pp. 030802262097951
Author(s):  
Lizette Norin ◽  
Björn Slaug ◽  
Maria Haak ◽  
Susanne Iwarsson
Keyword(s):  
Older Adults ◽  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
Occupational Performance ◽  
Environmental Barriers ◽  
Cord Injury ◽  
Long Term Follow Up ◽  
Societal Level ◽  
The Individual

Introduction Adults with spinal cord injuries are living longer than previously, and a majority are living in ordinary housing in the community. Housing accessibility is important for maintaining independent occupational performance for this population, but knowledge in this area is insufficient. We investigated housing adaptations and current accessibility problems among older adults with long-standing (>10 years) spinal cord injuries. Method Data from home visits among 122 older adults with spinal cord injuries in Sweden were used. Housing adaptations and environmental barriers were descriptively analysed. Findings Kitchens, entrances, and hygiene areas were common locations for housing adaptations and environmental barriers that generated accessibility problems. The most common adaptations were ramps, wheelchair-accessible stovetops, and ceiling-lifts. Wall-mounted cupboards and high shelves (kitchen), inaccessible storage areas (outside the dwelling), and a lack of grab bars (hygiene area) generated the most accessibility problems. Conclusion Despite housing adaptations, there are considerable accessibility problems in the dwellings of older adults with long-standing spinal cord injuries in Sweden, indicating that long-term follow-up of the housing situation of this population is necessary. Focusing on accessible housing as a prerequisite for occupational performance is at the core of occupational therapy, deserving attention on the individual as well as the societal level.

scholarly journals Genetic Susceptibility to Periodontal Disease in Down Syndrome: A Case-Control Study

2021 ◽  
Vol 22 (12) ◽  
pp. 6274
Author(s):  
María Fernández ◽  
Alicia de de Coo ◽  
Inés Quintela ◽  
Eliane García ◽  
Márcio Diniz-Freitas ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Metabolic Pathways ◽  
Nominal Significance ◽  
Severe Periodontitis ◽  
Gene Level ◽  
Individual Marker ◽  
The Individual ◽  
Control Study ◽  
Marker Level

Severe periodontitis is prevalent in Down syndrome (DS). This study aimed to identify genetic variations associated with periodontitis in individuals with DS. The study group was distributed into DS patients with periodontitis (n = 50) and DS patients with healthy periodontium (n = 36). All samples were genotyped with the “Axiom Spanish Biobank” array, which contains 757,836 markers. An association analysis at the individual marker level using logistic regression, as well as at the gene level applying the sequence kernel association test (SKAT) was performed. The most significant genes were included in a pathway analysis using the free DAVID software. C12orf74 (rs4315121, p = 9.85 × 10−05, OR = 8.84), LOC101930064 (rs4814890, p = 9.61 × 10−05, OR = 0.13), KBTBD12 (rs1549874, p = 8.27 × 10−05, OR = 0.08), PIWIL1 (rs11060842, p = 7.82 × 10−05, OR = 9.05) and C16orf82 (rs62030877, p = 8.92 × 10−05, OR = 0.14) showed a higher probability in the individual analysis. The analysis at the gene level highlighted PIWIL, MIR9-2, LHCGR, TPR and BCR. At the signaling pathway level, PI3K-Akt, long-term depression and FoxO achieved nominal significance (p = 1.3 × 10−02, p = 5.1 × 10−03, p = 1.2 × 10−02, respectively). In summary, various metabolic pathways are involved in the pathogenesis of periodontitis in DS, including PI3K-Akt, which regulates cell proliferation and inflammatory response.

scholarly journals Corruption, Taxation and the Impact on the Shadow Economy

Economies ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 18 ◽  
Author(s):  
Daniel Němec ◽  
Eva Kotlánová ◽  
Igor Kotlán ◽  
Zuzana Machová
Keyword(s):  
Tax Evasion ◽  
Capital Accumulation ◽  
Shadow Economy ◽  
Labour Force ◽  
Destructive Effect ◽  
Eu Member States ◽  
Initial Assumption ◽  
The Individual ◽  
The Impact

While assessing the economic impacts of corruption, the corruption-related transmission channels which influence taxation as such have to be duly considered. Taking the example of the Czech Republic, this article aims to evaluate the impacts corruption has on the size of the shadow economy as well as on the individual sources of long-term economic growth, making use of a transmission channel through which corruption affects the tax burden components. Using the method of an extended DSGE model, it confirms the initial assumption that an increase in perceived corruption supports the shadow economy’s growth, but at the same time, it demonstrates that corruption and especially its perception has a significantly different effect on two key areas—the capital accumulation and the labour force size. It further identifies another sector of the economy representing taxes which are prone to tax evasion while asserting that corruption has a much more destructive effect on this sector of the economy, offering generalized implications for other post-communist EU member states in a similar situation.

scholarly journals Detection of epileptic activity in presumably normal EEG

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Sara Baldini ◽  
Francesca Pittau ◽  
Gwenael Birot ◽  
Vincent Rochas ◽  
Miralena I Tomescu ◽  
...  
Keyword(s):  
Focal Epilepsy ◽  
Epileptic Activity ◽  
Scalp Eeg ◽  
Vigilance State ◽  
Explained Variance ◽  
Long Term Monitoring ◽  
Interictal Discharges ◽  
The Individual ◽  
Term Monitoring

Abstract Monitoring epileptic activity in the absence of interictal discharges is a major need given the well-established lack of reliability of patients’ reports of their seizures. Up to now, there are no other tools than reviewing the seizure diary; however, seizures may not be remembered or dismissed voluntarily. In the present study, we set out to determine if EEG voltage maps of epileptogenic activity in individual patients can help to identify disease activity, even if their scalp EEG appears normal. Twenty-five patients with pharmacoresistant focal epilepsy were included. For each patient, 6 min of EEG with spikes (yes-spike) and without visually detectable epileptogenic discharges (no-spike) were selected from long-term monitoring recordings (EEG 31–37 channels). For each patient, we identified typical discharges, calculated their average and the corresponding scalp voltage map (‘spike-map’). We then fitted the spike-map for each patient on their (i) EEG epochs with visible spikes, (ii) epochs without any visible spike and (iii) EEGs of 48 controls. The global explained variance was used to estimate the presence of the spike-maps. The individual spike-map occurred more often in the spike-free EEGs of patients compared to EEGs of healthy controls (P = 0.001). Not surprisingly, this difference was higher if the EEGs contained spikes (P < 0.001). In patients, spike-maps were more frequent per second (P < 0.001) but with a shorter mean duration (P < 0.001) than in controls, for both no-spike and yes-spike EEGs. The amount of spike-maps was unrelated to clinical variables, like epilepsy severity, drug load or vigilance state. Voltage maps of spike activity are present very frequently in the scalp EEG of patients, even in presumably normal EEG. We conclude that spike-maps are a robust and potentially powerful marker to monitor subtle epileptogenic activity.

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