Biology subjects

Poll, S.

Publications and source records attributed to Poll, S..

6 recordsLinked to original sources

bioRxiv2024

Deficiency of actin depolymerizing factors ADF/Cfl1 in microglia decreases motility and impairs memory

Microglia are highly motile cells that play a crucial role in the central nervous system in health and disease. Here we show that actin depolymerizing factors ADF and Cofilin1 (Cfl1) are key factors of microglia integrity and function. We found a profound morphological phenotype in absence of ADF and Cfl1 in microglia. In vivo two-photon imaging of microglia with ADF/Cfl1-KO revealed reduced microglial fine processes motility and impaired microglia migration towards a laser-induced lesion. We found increased accumulation of stabilized F-actin and altered microtubule dynamics in ADF/Cfl1-KO microglia, indicating that ADF/Cfl1 are necessary for microglial cytoskeleton dynamics. Interestingly, microglial ADF/Cfl1-deficiency decreased learning and memory, suggesting that impaired microglial cytoskeleton dynamics affect neuronal functions relevant for cognition. Our results reveal a fundamental role of ADF/Cfl1 in microglia function and underscore the importance of these innate immune cells for higher cognitive functions.

neuroscience↗

bioRxiv2024

Three-photon in vivo imaging of neurons and glia in the medial prefrontal cortex with sub-cellular resolution

The medial prefrontal cortex (mPFC) is important for higher cognitive functions, including working memory, decision making, and emotional control. In vivo recordings of neuronal activity in the mPFC have been achieved via invasive electrical and optical approaches. Here we apply low invasive three-photon in vivo imaging in the mPFC of the mouse at unprecedented depth. Specifically, we measure neuronal and astrocytic Ca2+-transient parameters in awake head-fixed mice up to a depth of 1700 {micro}m. Furthermore, we longitudinally record dendritic spine density (0.41 {+/-}0.07 {micro}m-1) deeper than 1 mm for a week. Using 1650 nm wavelength to excite red fluorescent microglia, we quantify their processes motility (58.9 {+/-}2% turnover rate) at previously unreachable depths (1100 {micro}m). We establish three-photon imaging of the mPFC enabling neuronal and glial recordings with subcellular resolution that will pave the way for novel discoveries in this brain region.

neuroscience↗

bioRxiv2020

Elevated expression of complement C4 in the mouse prefrontal cortex causes schizophrenia-associated phenotypes

Accumulating evidence supports immune involvement in the pathogenesis of schizophrenia, a severe psychiatric disorder. In particular, high expression variants of C4, a gene of the innate immune complement system, were shown to confer susceptibility to schizophrenia. However, how elevated C4 expression may impact brain circuits remains largely unknown. We used in utero electroporation to overexpress C4 in the mouse prefrontal cortex (PFC). We found reduced glutamatergic input to pyramidal cells of juvenile and adult, but not of newborn C4-overexpressing (C4-OE) mice, together with decreased spine density, which mirrors spine loss observed in the schizophrenic cortex. Using time-lapse two-photon imaging in vivo, we observed that these deficits were associated with decreased dendritic spine gain and elimination in juvenile C4-OE mice, which may reflect poor formation and/or stabilization of immature spines. In juvenile and adult C4-OE mice we found evidence for NMDA receptor hypofunction, another schizophrenia-associated phenotype, and synaptic accumulation of calcium-permeable AMPA receptors. Alterations in cortical GABAergic networks have been repeatedly associated with schizophrenia. We found that functional GABAergic transmission was reduced in C4-OE mice, in line with diminished GABA release probability from parvalbumin interneurons, lower GAD67 expression and decreased intrinsic excitability in parvalbumin interneurons. These cellular abnormalities were associated with working memory impairment. Our results substantiate the causal relationship between an immunogenetic risk factor and several distinct cortical endophenotypes of schizophrenia, and shed light on the underlying cellular mechanisms.

neuroscience↗

bioRxiv2019

Microglia motility depends on neuronal activity andpromotes structural plasticity in the hippocampus

Microglia, the resident immune cells of the brain, play a complex role in health and disease. They actively survey the brain parenchyma by physically interacting with other cells and structurally shaping the brain. Yet, the mechanisms underlying microglia motility and their significance for synapse stability, especially during adulthood, remain widely unresolved. Here we investigated the impact of neuronal activity on microglia motility and its implication for synapse formation and survival. We used repetitive two-photon in vivo imaging in the hippocampus of awake mice to simultaneously study microglia motility and their interaction with synapses. We found that microglia process motility depended on neuronal activity. Simultaneously, more dendritic spines emerged in awake compared to anesthetized mice. Interestingly, microglia contact rates with individual dendritic spines were associated with their stability. These results suggest that microglia are not only sensing neuronal activity, but participate in synaptic rewiring of the hippocampus during adulthood, which has profound relevance for learning and memory processes.

neuroscience↗

bioRxiv2018

Restoring memory by optogenetic synchronization of hippocampal oscillations in an Alzheimer’s disease mouse model

Disrupted neural oscillations are a feature of Alzheimers disease (AD). We observed reduced frequency of theta oscillations in the hippocampal local field potential (LFP) in a mouse model of beta-amyloidosis. By restoring the temporal organization of theta oscillations using LFP-guided closed-loop optogenetic stimulation of parvalbumin-positive interneurons, we could rescue memory deficits of APP/PS1 mice in the novel object recognition test.

neuroscience↗

bioRxiv2018

Memory trace superimposition impairs recall in a mouse model of AD

Learning and memory processes depend on the hippocampus and are impaired in Alzheimers disease (AD). Active neuronal ensembles form an engram by encoding information during learning. Their reactivation is required for memory recall. However, it remains unresolved whether the engram in CA1 principal neurons is impaired under AD-like conditions. We used two-photon in vivo imaging to visualize the expression of the immediate early gene c-fos within CA1 neurons during contextual fear conditioning and retrieval. Surprisingly, we identified engrams in wild-type mice and in the mouse model of AD indicating intact memory formation. However, under AD-like conditions engrams were superimposed by a high number of newly recruited fosGFP+ neurons during memory recall. This superimposition resembled the network configuration of wild-type mice exposed to a novel context. Artificial superimposition of the memory trace during recall in wild-type mice was sufficient to induce memory impairment. Thus, we propose superimposition of the CA1 memory trace as a mechanism for memory impairment in a mouse model of AD.\n\nHighlightsO_LIDecreased fosGFP expression in direct vicinity to amyloid-{beta} plaques\nC_LIO_LIIntact engram in CA1 of APP/PS1 mice\nC_LIO_LIImpurity of the retrieval network in CA1 is sufficient to impair memory recall\nC_LI\n\nPoll et al. present a novel mechanism for memory impairment in a mouse model of AD. The potential memory trace was found intact in the CA1 region of the hippocampus. However, excessive neuronal activity during retrieval, was superimposing the memory trace in a mouse model of AD.

neuroscience↗