Three-dimensional spatial selectivity of hippocampal neurons during space flight

Background: Processing of the amyloid-β protein precursor (AβPP) is neurophysiologically important due to the resulting fragments that regulate synapse biology, as well as potentially harmful due to generation of the 42 amino acid long amyloid β-peptide (Aβ 42), which is a key player in Alzheimer’s disease. Objective: Our aim was to clarify the subcellular locations of the amyloidogenic AβPP processing in primary neurons, including the intracellular pools of the immediate substrate, AβPP C-terminal fragment (APP-CTF) and the product (Aβ 42). To overcome the difficulties of resolving these compartments due to their small size, we used super-resolution microscopy. Methods: Mouse primary hippocampal neurons were immunolabelled and imaged by stimulated emission depletion (STED) microscopy, including three-dimensional, three-channel imaging and image analyses. Results: The first (β-secretase) and second (γ-secretase) cleavages of AβPP were localized to functionally and distally distinct compartments. The β-secretase cleavage was observed in early endosomes, where we were able to show that the liberated N- and C-terminal fragments were sorted into distinct vesicles budding from the early endosomes in soma. Lack of colocalization of Aβ 42 and APP-CTF in soma suggested that γ-secretase cleavage occurs in neurites. Indeed, APP-CTF was, in line with Aβ 42 in our previous study, enriched in the presynapse but absent from the postsynapse. In contrast, full-length AβPP was not detected in either the pre- or the postsynaptic side of the synapse. Furthermore, we observed that endogenously produced and endocytosed Aβ 42 were localized in different compartments. Conclusion: These findings provide critical super-resolved insight into amyloidogenic AβPP processing in primary neurons.

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Analysis of Three-Dimensional Spatial Selectivity for Rician Channel

Radioengineering ◽

10.13164/re.2018.0249 ◽

2018 ◽

Vol 27 (1) ◽

pp. 249-255 ◽

Cited By ~ 1

Author(s):

D. Du ◽

X. Zeng ◽

X. Jian ◽

F. Yu ◽

L. Miao

Keyword(s):

Three Dimensional ◽

Spatial Selectivity ◽

Rician Channel

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Hippocampal Place-Cell Firing During Movement in Three-Dimensional Space

Journal of Neurophysiology ◽

10.1152/jn.2001.85.1.105 ◽

2001 ◽

Vol 85 (1) ◽

pp. 105-116 ◽

Cited By ~ 44

Author(s):

James J. Knierim ◽

Bruce L. McNaughton

Keyword(s):

Hippocampal Neurons ◽

Horizontal Plane ◽

Three Dimensional ◽

Place Cell ◽

Place Cells ◽

Limbic Cortex ◽

Head Direction ◽

Head Direction Cells ◽

Recording Apparatus ◽

Place Fields

“Place” cells of the rat hippocampus are coupled to “head direction” cells of the thalamus and limbic cortex. Head direction cells are sensitive to head direction in the horizontal plane only, which leads to the question of whether place cells similarly encode locations in the horizontal plane only, ignoring the z axis, or whether they encode locations in three dimensions. This question was addressed by recording from ensembles of CA1 pyramidal cells while rats traversed a rectangular track that could be tilted and rotated to different three-dimensional orientations. Cells were analyzed to determine whether their firing was bound to the external, three-dimensional cues of the environment, to the two-dimensional rectangular surface, or to some combination of these cues. Tilting the track 45° generally provoked a partial remapping of the rectangular surface in that some cells maintained their place fields, whereas other cells either gained new place fields, lost existing fields, or changed their firing locations arbitrarily. When the tilted track was rotated relative to the distal landmarks, most place fields remapped, but a number of cells maintained the same place field relative to the x-y coordinate frame of the laboratory, ignoring the z axis. No more cells were bound to the local reference frame of the recording apparatus than would be predicted by chance. The partial remapping demonstrated that the place cell system was sensitive to the three-dimensional manipulations of the recording apparatus. Nonetheless the results were not consistent with an explicit three-dimensional tuning of individual hippocampal neurons nor were they consistent with a model in which different sets of cells are tightly coupled to different sets of environmental cues. The results are most consistent with the statement that hippocampal neurons can change their “tuning functions” in arbitrary ways when features of the sensory input or behavioral context are altered. Understanding the rules that govern the remapping phenomenon holds promise for deciphering the neural circuitry underlying hippocampal function.

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Long-Term Culture of Rat Hippocampal Neurons at Low Density in Serum-Free Medium: Combination of the Sandwich Culture Technique with the Three-Dimensional Nanofibrous Hydrogel PuraMatrix

PLoS ONE ◽

10.1371/journal.pone.0102703 ◽

2014 ◽

Vol 9 (7) ◽

pp. e102703 ◽

Cited By ~ 20

Author(s):

Ai Kaneko ◽

Yoshiyuki Sankai

Keyword(s):

Hippocampal Neurons ◽

Three Dimensional ◽

Culture Technique ◽

Low Density ◽

Serum Free Medium ◽

Free Medium ◽

Serum Free ◽

Long Term Culture ◽

Sandwich Culture

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Multipath Directivity and Spatial Selectivity in Three-Dimensional Wireless Channels

IEEE Transactions on Antennas and Propagation ◽

10.1109/tap.2009.2021873 ◽

2009 ◽

Vol 57 (7) ◽

pp. 2147-2154

Author(s):

D.G. Valchev ◽

D. Brady

Keyword(s):

Wireless Channels ◽

Three Dimensional ◽

Spatial Selectivity

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Neuronal hibernation following hippocampal demyelination

Acta Neuropathologica Communications ◽

10.1186/s40478-021-01130-9 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Selva Baltan ◽

Safdar S. Jawaid ◽

Anthony M. Chomyk ◽

Grahame J. Kidd ◽

Jacqueline Chen ◽

...

Keyword(s):

Dendritic Spines ◽

Hippocampal Neurons ◽

Molecular Mechanisms ◽

Three Dimensional ◽

Long Term Potentiation ◽

Synaptic Function ◽

Mammalian Brain ◽

Gene Transcript ◽

Ca1 Neurons

AbstractCognitive dysfunction occurs in greater than 50% of individuals with multiple sclerosis (MS). Hippocampal demyelination is a prominent feature of postmortem MS brains and hippocampal atrophy correlates with cognitive decline in MS patients. Cellular and molecular mechanisms responsible for neuronal dysfunction in demyelinated hippocampi are not fully understood. Here we investigate a mouse model of hippocampal demyelination where twelve weeks of treatment with the oligodendrocyte toxin, cuprizone, demyelinates over 90% of the hippocampus and causes decreased memory/learning. Long-term potentiation (LTP) of hippocampal CA1 pyramidal neurons is considered to be a major cellular readout of learning and memory in the mammalian brain. In acute slices, we establish that hippocampal demyelination abolishes LTP and excitatory post-synaptic potentials of CA1 neurons, while pre-synaptic function of Schaeffer collateral fibers is preserved. Demyelination also reduced Ca2+-mediated firing of hippocampal neurons in vivo. Using three-dimensional electron microscopy, we investigated the number, shape (mushroom, stubby, thin), and post-synaptic densities (PSDs) of dendritic spines that facilitate LTP. Hippocampal demyelination did not alter the number of dendritic spines. Surprisingly, dendritic spines appeared to be more mature in demyelinated hippocampi, with a significant increase in mushroom-shaped spines, more perforated PSDs, and more astrocyte participation in the tripartite synapse. RNA sequencing experiments identified 400 altered transcripts in demyelinated hippocampi. Gene transcripts that regulate myelination, synaptic signaling, astrocyte function, and innate immunity were altered in demyelinated hippocampi. Hippocampal remyelination rescued synaptic transmission, LTP, and the majority of gene transcript changes. We establish that CA1 neurons projecting demyelinated axons silence their dendritic spines and hibernate in a state that may protect the demyelinated axon and facilitates functional recovery following remyelination.

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