Biology subjects

Hall, S. P.

Publications and source records attributed to Hall, S. P..

4 recordsLinked to original sources

bioRxiv2024

Cortical layer-specific and cell type-specific dendritic expression of Arc (Arg 3.1) in an in vitro model of slow-wave sleep

An abundance of evidence shows sleep homeostatically regulates synaptic plasticity and memory consolidation but the underlying molecular regulators of this important function of sleep have been difficult to directly elucidate. Arc is an immediate early gene that has a fundamental role in several aspects of synaptic plasticity including regulation and maintenance. Using a physiological brain slice model of slow-wave sleep, here we show that Arc protein has a characteristic spatial and cell-type specific distribution during persistent sleep-related delta oscillations in neocortical slices, which may correlate with aspects of sleep-dependent regulation of synaptic plasticity in cortical regions. In delta oscillating slices, Arc is highly expressed in layer 2/3 dendrites of the primary and secondary association cortex and this dendritic localisation is specific to intrinsically bursting cells (IB) whose cell bodies are in layer 5. Moreover, Arc immunopositive dendrites are clustered together arranged in a quasi hexagonal arrangement with a spacing of [~] 50 {micro}m between clusters. The cytoarchitectural distribution of Arc across the association cortex has implications for the mechanisms of sleep and for the synaptic homeostasis hypothesis regarding the function of sleep.

neuroscience↗

bioRxiv2018

Insoluble Aβ overexpression in an App knock-in mouse model alters microstructure and gamma oscillations in the prefrontal cortex, and social and anxiety-related behaviours

We studied two new App knock-in mice models of Alzheimers disease (AppNL-F and AppNL-G-F), which generate elevated levels of A{beta}40 and A{beta}42 without the confounds associated with APP overexpression. This enabled us to assess changes in anxiety-related and social behaviours, and neural alterations potentially underlying such changes, driven specifically by A{beta} accumulation. AppNL-G-F knock-in mice exhibited subtle deficits in tasks assessing social memory, but not in social motivation tasks. In anxiety-assessing tasks, AppNL-G-F knock-in mice exhibited: 1) increased thigmotaxis in the Open Field (OF), yet; 2) reduced closed-arm, and increased open-arm, time in the Elevated Plus Maze (EPM). Their ostensibly-anxiogenic OF profile, yet ostensibly-anxiolytic EPM profile, could hint at altered cortical mechanisms affecting decision-making (e.g. disinhibition), rather than simple core deficits in emotional motivation. Consistent with this possibility, alterations in microstructure, glutamatergic-dependent gamma oscillations, and glutamatergic gene expression were all observed in the prefrontal cortex, but not the amygdala, of AppNL-G-F knock-in mice. Thus, insoluble A{beta} overexpression drives prefrontal cortical alterations, potentially underlying changes in social and anxiety-related behavioural tasks.\n\nHighlightsO_LIAppNL-G-F KI mice displayed differing anxiety behaviours in two tests of anxiety.\nC_LIO_LIPrefrontal gamma was no longer NMDA-receptor dependent in AppNL-G-F KI mice.\nC_LIO_LIPrefrontal expression of Grin2b was reduced in AppNL-G-F KI mice.\nC_LIO_LIDTI found structural alterations in the hippocampus and prefrontal cortex in AppNL-G-F KI mice.\nC_LI

neuroscience↗

bioRxiv2018

Cross-fostering in rodents causes region-specific alterations in entorhinal cortical gamma rhythms associated with NMDA receptor dysfunction

There has recently been a large increase in the number of children placed in foster care in the United States and Europe. While this is the least worst scenario for those with a lack of appropriate biological care, it is recognised that these children are exposed to major stressors correlated with behavioural changes, particularly in the realm of social cognition into adulthood. Here we model foster care in rodents: rat pups are removed from their biological mother and placed with a non-genetically related dam. This prevented the entorhinal cortex from generating patterns of gamma rhythms required for normal parahippocampal function relevant to social interaction. These changes correlated with a reduction in NMDA receptor-mediated excitation, and changes in parvalbumin expression in interneurons. These data suggest that early life care delivered by a non-biological parent may disrupt social behaviour but, in contrast, generate neurobiological changes antagonistic to those currently associated with psychosis.\n\nSignificance StatementCross fostering is an effective approach for delineating the effect of environment from genetic influences upon behavior. This involves removal of pups from one mother and transfer to another lactating dam. This manipulation is considered as a mild form of early life stress, producing neurobehavioral changes such as alterations in social interaction. We demonstrate that cross fostering produces changes in the ability of cortical microcircuits to generate oscillatory rhythms, in particular the gamma rhythm, in brain regions important for social cognition. This reduction in gamma rhythmogenesis is related to a reduction in synaptic drive provided by the NMDA receptor. One implication of this work is that the modulation of NMDA receptors offers a potential therapeutic strategy for disorders involving impaired sociability.

neuroscience↗

bioRxiv2018

Levetiracetam and Rufinamide are effective at supressing spike and wave seizure activity in an in vitro model of absence epilepsy.

Spike-and-wave discharges (SpW) are seen in absence-type epilepsies. They are heterogeneous in terms of their clinical burden and their electrographic signature, which is used to classify different types of absence seizures; typical absence, in which SpW frequency is 3-4Hz and atypical absence, which shows a slower 1-2Hz frequency. Treatment of SpW varies dependent upon the syndrome, but both Valproic Acid (VPA) and Ethosuximide (ESM) are shown to be effective in controlling typical absence seizures. Other anti-epileptics (AEDs), Levetiracetam (LEV) and Rufinamide (RUF), have shown promise in treating absence epilepsies and their associated syndromes. Here we examine the efficacy of these AEDs on an in vitro model of SpW.\n\nBoth LEV and RUF show an effective reduction in both the number of SpW events and the spike component amplitude; VPA shows no effect, whilst ESM enhances the spike amplitude. Phenytoin exacerbates the SpW activity, increasing both the number of SpW, amplitude of the SpW and the number of spikes within each event. These data suggest that both LEV and RUF could be effective in the treatment of absence-type epilepsies. They also suggest this model could be an effective tool to test other AEDs aimed at treating atypical absence syndromes.

neuroscience↗