CKAMP44 controls synaptic function and strength of relay neurons during early development of the dorsal lateral geniculate nucleus

Hetsch, Florian; Wang, Danni; Chen, Xufeng; Zhang, Jiong; Aslam, Muhammad; Kegel, Marcel; Tonner, Henrik; Grus, Franz H.; Engelhardt, Jakob von

doi:10.1113/jp283172

Cited by 4 publications

(1 citation statement)

References 42 publications

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“…The total number of cells used per age and region is given in Supplementary Material. References: Cerebellum P6-P10 38 , P10-P13 39 , P35-P43 40 ; Thalamus P9-P30 41 (B) The values of Branch Length (Lsegment), Branching Order and total process length are directly estimated from the morphology using the function stat_tree in the Trees Matlab Toolbox.…”

Section: Discussionmentioning

confidence: 99%

Diffusion MRS tracks distinct trajectories of neuronal development in the cerebellum and thalamus of rat neonates

Ligneul,

Qiu,

Clarke

et al. 2023

Preprint

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The brain develops in a nonuniform manner, with local bursts of plasticity. In mammals, the cerebellum remains in a vulnerable developmental state longer than the neocortex, making it a potential hotspot for neurodevelopmental disorders. Cerebellar neurons, and more particularly Purkinje cells, have an altered morphology in forms of autism spectrum disorders or in Down syndrome. However, it is currently impossible to non-invasively assess cerebellar cell-structure during early development. Here we use diffusion-weighted magnetic resonance spectroscopy in combination with microstructural modelling to longitudinally track cerebellar cell-specific development from P5 to P30 in rat neonates. Tracking metabolite diffusion allows us to probe cell-specific developmental trajectories. Additionally, by comparing different analytical and biophysical microstructural models we can follow the differential contribution of cell bodies and neurites during development. The thalamus served as a control region to assess the sensitivity of our method to microstructural differences between the regions. We found significant differences between cerebellar and thalamic metabolites diffusion properties. We report a decreased sphere fraction (or an increased neurite fraction) with age for taurine and total creatine in the cerebellum, marking dendritic growth. Surprisingly, we also report a U-shape trend for segment length (the distance between two embranchments in a dendritic tree) in the cerebellum with age matching morphometry of openly available 3D-Purkinje reconstructions. Results demonstrate that diffusion-weighted MRS probes early cerebellar neuronal development non-invasively.

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Section: Discussionmentioning

confidence: 99%

Diffusion MRS tracks distinct trajectories of neuronal development in the cerebellum and thalamus of rat neonates

Ligneul,

Qiu,

Clarke

et al. 2023

Preprint

View full text Add to dashboard Cite

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Exploring the role of AMPA receptor auxiliary proteins in synaptic functions and diseases

Qneibi,

Bdir,

Bdair

et al. 2024

The FEBS Journal

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α‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) ionotropic glutamate receptors (AMPARs) mediate rapid excitatory synaptic transmission in the mammalian brain, primarily driven by the neurotransmitter glutamate. The modulation of AMPAR activity, particularly calcium‐permeable AMPARs (CP‐AMPARs), is crucially influenced by various auxiliary subunits. These subunits are integral membrane proteins that bind to the receptor's core and modify its functional properties, including ion channel kinetics and receptor trafficking. This review comprehensively catalogs all known AMPAR auxiliary proteins, providing vital insights into the biochemical mechanisms governing synaptic modulation and the specific impact of CP‐AMPARs compared to their calcium‐impermeable AMPA receptor (CI‐AMPARs). Understanding the complex interplay between AMPARs and their auxiliary subunits in different brain regions is essential for elucidating their roles in cognitive functions such as learning and memory. Importantly, alterations in these auxiliary proteins' expression, function or interactions have been implicated in various neurological disorders. Aberrant signaling through CP‐AMPARs, in particular, is associated with severe synaptic dysfunctions across neurodevelopmental, neurodegenerative and psychiatric conditions. Targeting the distinct properties of AMPAR‐auxiliary subunit complexes, especially those involving CP‐AMPARs, could disclose new therapeutic strategies, potentially allowing for more precise interventions in treating complex neuronal disorders.

show abstract

Diffusion MRS tracks distinct trajectories of neuronal development in the cerebellum and thalamus of rat neonates

Ligneul,

Qiu,

Clarke

et al. 2024

Preprint

View full text Add to dashboard Cite

It is currently impossible to non-invasively assess cerebellar cell structure during early development. Here we propose a novel approach to non-invasively and longitudinally track cell-specific development using diffusion-weighted magnetic resonance spectroscopy in combination with microstructural modelling. Tracking metabolite diffusion allows us to probe cell-specific developmental trajectories in the cerebellum and thalamus of healthy rat neonates from post-natal day (P) 5 to P30. Additionally, by comparing different analytical and biophysical microstructural models we can follow the differential contribution of cell bodies and neurites during development. The thalamus serves as a control region to assess the sensitivity of our method to microstructural differences between the regions. We found significant differences between cerebellar and thalamic metabolites diffusion properties. For most metabolites, the signal attenuation is stronger in the thalamus, suggesting less restricted diffusion compared to the cerebellum. There is also a trend for lower signal attenuation and lower ADCs with increasing age, suggesting increasing restriction of metabolite diffusion. This is particularly striking for taurine in the thalamus. We use biophysical modelling to interpret these differences. We report a decreased sphere fraction (or an increased neurite fraction) with age for taurine and total creatine in the cerebellum, marking dendritic growth. Surprisingly, we also report a U-shape trend for segment length (the distance between two embranchments in a dendritic tree) in the cerebellum agreeing with age-matching morphometry of openly available 3D-Purkinje reconstructions. Results demonstrate that diffusion-weighted MRS probes early cerebellar neuronal development non-invasively.

show abstract

CKAMP44 controls synaptic function and strength of relay neurons during early development of the dorsal lateral geniculate nucleus

Abstract: support-information-section).

Cited by 4 publications

References 42 publications

Diffusion MRS tracks distinct trajectories of neuronal development in the cerebellum and thalamus of rat neonates

Diffusion MRS tracks distinct trajectories of neuronal development in the cerebellum and thalamus of rat neonates

Exploring the role of AMPA receptor auxiliary proteins in synaptic functions and diseases

Diffusion MRS tracks distinct trajectories of neuronal development in the cerebellum and thalamus of rat neonates

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