scholarly journals Proximodistal organization of the CA2 hippocampal area

2018 ◽  
Author(s):  
I. Fernandez-Lamo ◽  
D. Gomez-Dominguez ◽  
A. Sanchez-Aguilera ◽  
E. Cid ◽  
M. Valero ◽  
...  
Keyword(s):  
Social Memory ◽  
Single Cells ◽  
Memory Task ◽  
Gamma Oscillations ◽  
Synaptic Activity ◽  
Organizational Principle ◽  
Hippocampal Area ◽  
Surrounding Areas ◽  
And Function ◽  
Membrane Potential Fluctuations

The proximodistal axis is considered a major organizational principle of the hippocampus. Interfacing between the hippocampus and other brain systems, the CA2 region apparently breaks this rule. Apart from its specific role in social memory, CA2 has been involved in temporal and contextual memory but mechanisms remain elusive. Here, we used intracellular and extracellular recordings followed by neurochemical identification of single-cells to evaluate CA2 and surrounding areas in the rat. We found marked proximodistal trends of synaptic activity, as well as in subthreshold membrane potentials and phase-locked firing coupled to theta and gamma oscillations. Opposite proximodistal correlations between membrane potential fluctuations and theta sinks and sources at different layers revealed influences from up to three different generators. CA2 memory engrams established after a social memory task reflected these trends. We suggest that the structure and function of CA2 is segregated along the proximodistal hippocampal axis.

scholarly journals CA2 neuronal activity controls hippocampal low gamma and ripple oscillations

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Georgia M Alexander ◽  
Logan Y Brown ◽  
Shannon Farris ◽  
Daniel Lustberg ◽  
Caroline Pantazis ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Cognitive Functions ◽  
Social Memory ◽  
Experimental System ◽  
Gamma Oscillations ◽  
Neuronal Populations ◽  
Prefrontal Cortical ◽  
Network Oscillations ◽  
Hippocampal Area

Hippocampal oscillations arise from coordinated activity among distinct populations of neurons and are associated with cognitive functions. Much progress has been made toward identifying the contribution of specific neuronal populations in hippocampal oscillations, but less is known about the role of hippocampal area CA2, which is thought to support social memory. Furthermore, the little evidence on the role of CA2 in oscillations has yielded conflicting conclusions. Therefore, we sought to identify the contribution of CA2 to oscillations using a controlled experimental system. We used excitatory and inhibitory DREADDs to manipulate CA2 neuronal activity and studied resulting hippocampal-prefrontal cortical network oscillations. We found that modification of CA2 activity bidirectionally regulated hippocampal and prefrontal cortical low-gamma oscillations and inversely modulated hippocampal ripple oscillations in mice. These findings support a role for CA2 in low-gamma generation and ripple modulation within the hippocampus and underscore the importance of CA2 in extrahippocampal oscillations.

scholarly journals The long noncoding RNA Synage regulates synapse stability and neuronal function in the cerebellum

2021 ◽  
Author(s):  
Fei Wang ◽  
Qianqian Wang ◽  
Baowei Liu ◽  
Lisheng Mei ◽  
Sisi Ma ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Cerebellar Atrophy ◽  
Synaptic Activity ◽  
Motor Dysfunction ◽  
Cerebellar Development ◽  
Full Spectrum ◽  
Density Reduction ◽  
Adult Mice ◽  
Synapse Density ◽  
And Function

AbstractThe brain is known to express many long noncoding RNAs (lncRNAs); however, whether and how these lncRNAs function in modulating synaptic stability remains unclear. Here, we report a cerebellum highly expressed lncRNA, Synage, regulating synaptic stability via at least two mechanisms. One is through the function of Synage as a sponge for the microRNA miR-325-3p, to regulate expression of the known cerebellar synapse organizer Cbln1. The other function is to serve as a scaffold for organizing the assembly of the LRP1-HSP90AA1-PSD-95 complex in PF-PC synapses. Although somewhat divergent in its mature mRNA sequence, the locus encoding Synage is positioned adjacent to the Cbln1 loci in mouse, rhesus macaque, and human, and Synage is highly expressed in the cerebella of all three species. Synage deletion causes a full-spectrum cerebellar ablation phenotype that proceeds from cerebellar atrophy, through neuron loss, on to synapse density reduction, synaptic vesicle loss, and finally to a reduction in synaptic activity during cerebellar development; these deficits are accompanied by motor dysfunction in adult mice, which can be rescued by AAV-mediated Synage overexpression from birth. Thus, our study demonstrates roles for the lncRNA Synage in regulating synaptic stability and function during cerebellar development.

scholarly journals Fragile X syndrome patient-derived neurons developing in the mouse brain show FMR1 -dependent phenotypes

2021 ◽  
Author(s):  
Marine A Krzisch ◽  
Hao A Wu ◽  
Bingbing Yuan ◽  
Troy W. Whitfield ◽  
X. Shawn Liu ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Neuronal Development ◽  
Fragile X ◽  
In Vitro Models ◽  
Synaptic Activity ◽  
Human Neurons ◽  
Induced Pluripotent ◽  
And Function ◽  
The Brain

Abnormal neuronal development in Fragile X syndrome (FXS) is poorly understood. Data on FXS patients remain scarce and FXS animal models have failed to yield successful therapies. In vitro models do not fully recapitulate the morphology and function of human neurons. Here, we co-injected neural precursor cells (NPCs) from FXS patient-derived and corrected isogenic control induced pluripotent stem cells into the brain of neonatal immune-deprived mice. The transplanted cells populated the brain and a proportion differentiated into neurons and glial cells. Single-cell RNA sequencing of transplanted cells revealed upregulated excitatory synaptic transmission and neuronal differentiation pathways in FXS neurons. Immunofluorescence analyses showed accelerated maturation of FXS neurons after an initial delay. Additionally, increased percentages of Arc- and Egr1-positive FXS neurons and wider dendritic protrusions of mature FXS striatal medium spiny neurons pointed to an increase in synaptic activity and synaptic strength as compared to control. This transplantation approach provides new insights into the alterations of neuronal development in FXS by facilitating physiological development of cells in a 3D context, and could be used to test new therapeutic compounds correcting neuronal development defects in FXS.

scholarly journals Theta and gamma hippocampal-neocortical oscillations during the episodic-like memory test: impairment in epileptogenic rats

2021 ◽  
Author(s):  
Anton E Malkov ◽  
Ludmila Shevkova ◽  
Alexandra Latyshkova ◽  
Valentina Kitchigina
Keyword(s):  
Episodic Memory ◽  
Memory Task ◽  
Gamma Oscillations ◽  
High Amplitude ◽  
Memory Test ◽  
Interictal Spikes ◽  
Paroxysmal Activity ◽  
Cortical Oscillations ◽  
Gamma Rhythms ◽  
Hippocampal Theta

Cortical oscillations in different frequency bands have been shown to be intimately involved in exploration of environment and cognition. Here, the local field potentials in the hippocampus, the medial prefrontal cortex (mPFC), and the medial entorhinal cortex (mEC) were recorded simultaneously in rats during the execution of the episodic-like memory task. The power of hippocampal theta (~4-10 Hz), slow gamma (~25-50 Hz), and fast gamma oscillations (~55-100 Hz) was analyzed in all structures examined. Particular attention was paid to the theta coherence between three mentioned structures. The modulation of the power of gamma rhythms by the phase of theta cycle during the execution of the episodic-like memory test by rats was also closely studied. Healthy rats and rats one month after kainate-induced status epilepticus (SE) were examined. Paroxysmal activity in the hippocampus (high amplitude interictal spikes), excessive excitability of animals, and the death of hippocampal and dentate granular cells in rats with kainate-evoked SE were observed, which indicated the development of seizure focus in the hippocampus (epileptogenesis). One month after SE, the rats exhibited a specific impairment of episodic memory for the what-where-when triad: unlike healthy rats, epileptogenic SE animals did not identify the objects during the test. This impairment was associated with the changes in the characteristics of theta and gamma rhythms and specific violation of theta coherence and theta/gamma coupling in these structures in comparison with the healthy animals. We believe that these disturbances in the cortical areas play a role in episodic memory dysfunction in kainate-treated animals. These findings can shed light on the mechanisms of cognitive deficit during epileptogenesis.

Long-term Memory Upscales Volume of Postsynaptic Densities in the Process that Requires Autophosphorylation of αCaMKII

2019 ◽  
Vol 30 (4) ◽  
pp. 2573-2585 ◽  
Author(s):  
Małgorzata Alicja Śliwińska ◽  
Anna Cały ◽  
Malgorzata Borczyk ◽  
Magdalena Ziółkowska ◽  
Edyta Skonieczna ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Smooth Endoplasmic Reticulum ◽  
Structural Data ◽  
Long Term Memory ◽  
Brain Circuits ◽  
Hippocampal Area ◽  
And Function ◽  
And Storage ◽  
Old Mice

Abstract It is generally accepted that formation and storage of memory relies on alterations of the structure and function of brain circuits. However, the structural data, which show learning-induced and long-lasting remodeling of synapses, are still very sparse. Here, we reconstruct 1927 dendritic spines and their postsynaptic densities (PSDs), representing a postsynaptic part of the glutamatergic synapse, in the hippocampal area CA1 of the mice that underwent spatial training. We observe that in young adult (5 months), mice volume of PSDs, but not the volume of the spines, is increased 26 h after the training. The training-induced growth of PSDs is specific for the dendritic spines that lack smooth endoplasmic reticulum and spine apparatuses, and requires autophosphorylation of αCaMKII. Interestingly, aging alters training-induced ultrastructural remodeling of dendritic spines. In old mice, both the median volumes of dendritic spines and PSDs shift after training toward bigger values. Overall, our data support the hypothesis that formation of memory leaves long-lasting footprint on the ultrastructure of brain circuits; however, the form of circuit remodeling changes with age.

scholarly journals Parallel analysis of tri-molecular biosynthesis with cell identity and function in single cells

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Samuel C. Kimmey ◽  
Luciene Borges ◽  
Reema Baskar ◽  
Sean C. Bendall
Keyword(s):  
Single Cells ◽  
Parallel Analysis ◽  
Cell Identity ◽  
And Function

scholarly journals Sleep-wake cycles drive daily dynamics of synaptic phosphorylation

Science ◽  
2019 ◽  
Vol 366 (6462) ◽  
pp. eaav3617 ◽  
Author(s):  
Franziska Brüning ◽  
Sara B. Noya ◽  
Tanja Bange ◽  
Stella Koutsouli ◽  
Jan D. Rudolph ◽  
...  
Keyword(s):  
Brain Function ◽  
Synaptic Function ◽  
Synaptic Activity ◽  
Regulation Of Transcription ◽  
Protein Abundance ◽  
Cellular Processes ◽  
Cytoskeleton Reorganization ◽  
And Function ◽  
Daily Changes ◽  
Rest Activity

The circadian clock drives daily changes of physiology, including sleep-wake cycles, through regulation of transcription, protein abundance, and function. Circadian phosphorylation controls cellular processes in peripheral organs, but little is known about its role in brain function and synaptic activity. We applied advanced quantitative phosphoproteomics to mouse forebrain synaptoneurosomes isolated across 24 hours, accurately quantifying almost 8000 phosphopeptides. Half of the synaptic phosphoproteins, including numerous kinases, had large-amplitude rhythms peaking at rest-activity and activity-rest transitions. Bioinformatic analyses revealed global temporal control of synaptic function through phosphorylation, including synaptic transmission, cytoskeleton reorganization, and excitatory/inhibitory balance. Sleep deprivation abolished 98% of all phosphorylation cycles in synaptoneurosomes, indicating that sleep-wake cycles rather than circadian signals are main drivers of synaptic phosphorylation, responding to both sleep and wake pressures.

scholarly journals Neuron-based high-content assay and screen for CNS active mitotherapeutics

2020 ◽  
Vol 6 (2) ◽  
pp. eaaw8702 ◽  
Author(s):  
Boglarka H. Varkuti ◽  
Miklos Kepiro ◽  
Ze Liu ◽  
Kyle Vick ◽  
Yosef Avchalumov ◽  
...  
Keyword(s):  
Small Molecule ◽  
Hippocampal Neurons ◽  
Mitochondrial Dynamics ◽  
Synaptic Activity ◽  
Glutamate Toxicity ◽  
Primary Neurons ◽  
Screening Assay ◽  
Dynamics And Function ◽  
Small Molecule Modulators ◽  
And Function

Impaired mitochondrial dynamics and function are hallmarks of many neurological and psychiatric disorders, but direct screens for mitotherapeutics using neurons have not been reported. We developed a multiplexed and high-content screening assay using primary neurons and identified 67 small-molecule modulators of neuronal mitostasis (MnMs). Most MnMs that increased mitochondrial content, length, and/or health also increased mitochondrial function without altering neurite outgrowth. A subset of MnMs protected mitochondria in primary neurons from Aβ(1–42) toxicity, glutamate toxicity, and increased oxidative stress. Some MnMs were shown to directly target mitochondria. The top MnM also increased the synaptic activity of hippocampal neurons and proved to be potent in vivo, increasing the respiration rate of brain mitochondria after administering the compound to mice. Our results offer a platform that directly queries mitostasis processes in neurons, a collection of small-molecule modulators of mitochondrial dynamics and function, and candidate molecules for mitotherapeutics.

Progressive feline pressure-overload: noninvasive assessment correlates with abnormalities in single cells

1993 ◽  
Vol 264 (4) ◽  
pp. H1307-H1314 ◽  
Author(s):  
P. S. Pollack ◽  
B. A. Bailey ◽  
R. Budjak ◽  
E. Fernandez ◽  
S. R. Houser
Keyword(s):  
Myocardial Dysfunction ◽  
Single Cells ◽  
Pressure Overload ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Septal Wall ◽  
Septal Wall Thickness ◽  
Feline Model ◽  
And Function ◽  
Fractional Shortening

Serial echocardiography and Doppler were used to monitor the progression of pressure-overload produced by banding the ascending aortas of young cats. The peak Doppler gradient across the band increased (as the animals grew in size) from 42 +/- 4.2 mmHg at 1 wk to 78 +/- 4.5 mmHg at 2-3 mos. Echocardiographic measurements of septal wall thickness increased significantly at 1 wk. Global ventricular function was unaltered in banded cats versus shams at each time point. However, in the subgroup of animals with an aortic-constricted area of < 0.025 cm2 at 1 wk, fractional shortening decreased by 40% at 2-3 mos. Contractile abnormalities were present in isolated myocytes from hypertrophied hearts. Mechanical function was more profoundly depressed in cells from hearts with echocardiographic evidence of ventricular decompensation. Echocardiographic and Doppler studies assessed cardiac size and function and identified indexes predictive of global and cellular myocardial dysfunction. The use of noninvasive techniques as a predictor of failure makes the feline model of progressive left ventricular pressure-overload useful for studies of cellular and molecular factors regulating not only the development of cardiac hypertrophy but also the transition from compensated hypertrophy to myocardial failure.

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