Dendritic Spine Density and LTP Induction in Cultured Hippocampal Slices

Collin, Carlos, Katsuyuki Miyaguchi, and Menahem Segal.Dendritic spine density and LTP induction in cultured hippocampal slices. J. Neurophysiol. 77: 1614–1623, 1997. Transverse hippocampal slices were cut from 8- to 9-day-old rats and maintained in an interface chamber for periods of 1–4 wk, in tissue culture conditions. Neurons in the slice preserved their spatial organization and connectivity. Dendritic spine density in CA1 neurons was very low at 1 wk in culture, and long, filopodia-like structures were abundant. Spine density increased in these neurons nearly threefold during the course of 3 wk in vitro, to approach values of those of the normal, in vivo hippocampus. The magnitude of long-term potentiation (LTP) of reactivity of CA1 to stimulation of CA3 neurons also increased during weeks in culture in parallel with the change in spine density. Chronic exposure of slices to drugs that interact with synaptic activity caused changes in their dendritic spine density. Blockade of the N-methyl-d-aspartate (NMDA) receptors with the receptor antagonist 2-aminophosphonovalerate (d-APV) or blockade of action potential discharges with tetrodotoxin (TTX) prevented dendritic spine development in immature cultures. Enhancing synaptic activity by blockade of GABAergic inhibition with picrotoxin did not affect spine density to a significant degree. d-APV-treated slices expressed larger LTP than controls. TTX-treated slices expressed smaller LTP than controls. Picrotoxin treated slices did not express LTP. It is proposed that LTP and dendritic spine density are correlated strongly during development, whereas they are not correlated in the more mature slice/culture of the hippocampus where spine density can be modulated by chronic exposure to blockers of synaptic activity, which will not affect LTP in a similar manner.

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The Polyadenosine RNA Binding Protein ZC3H14 is Required in Mice for Proper Dendritic Spine Density

10.1101/2020.10.08.331827 ◽

2020 ◽

Cited By ~ 1

Author(s):

Stephanie K. Jones ◽

Jennifer Rha ◽

Sarah Kim ◽

Kevin J. Morris ◽

Omotola F. Omotade ◽

...

Keyword(s):

Dendritic Spine ◽

Hippocampal Neurons ◽

Rna Binding ◽

Rna Binding Proteins ◽

Binding Protein ◽

Rna Binding Protein ◽

Spine Density ◽

Dendritic Spine Density

AbstractZC3H14 (Zinc finger CysCysCysHis domain-containing protein 14), an evolutionarily conserved member of a class of tandem zinc finger (CCCH) polyadenosine (polyA) RNA binding proteins, is associated with a form of heritable, nonsyndromic autosomal recessive intellectual disability. Previous studies of a loss of function mouse model, Zc3h14Δex13/Δex13, provide evidence that ZC3H14 is essential for proper brain function, specifically for working memory. To expand on these findings, we analyzed the dendrites and dendritic spines of hippocampal neurons from Zc3h14Δex13/Δex13 mice, both in situ and in vitro. These studies reveal that loss of ZC3H14 is associated with a decrease in total spine density in hippocampal neurons in vitro as well as in the dentate gyrus of 5-month old mice analyzed in situ. This reduction in spine density in vitro results from a decrease in the number of mushroom-shaped spines, which is rescued by exogenous expression of ZC3H14. We next performed biochemical analyses of synaptosomes prepared from whole wild-type and Zc3h14Δex13/Δex13 mouse brains to determine if there are changes in steady state levels of postsynaptic proteins upon loss of ZC3H14. We found that ZC3H14 is present within synaptosomes and that a crucial postsynaptic protein, CaMKIIα, is significantly increased in these synaptosomal fractions upon loss of ZC3H14. Together, these results demonstrate that ZC3H14 is necessary for proper dendritic spine density in cultured hippocampal neurons and in some regions of the mouse brain. These findings provide insight into how a ubiquitously expressed RNA binding protein leads to neuronal-specific defects that result in brain dysfunction.

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Rapid Effects of Estradiol on Dendritic Spines and Synaptic Plasticity in the Male and Female Hippocampus

Estrogens and Memory ◽

10.1093/oso/9780190645908.003.0004 ◽

2020 ◽

pp. 38-47

Author(s):

Asami Kato ◽

Gen Murakami ◽

Yasushi Hojo ◽

Sigeo Horie ◽

Suguru Kawato

Keyword(s):

Synaptic Plasticity ◽

Dendritic Spine ◽

Hippocampal Neurons ◽

Molecular Mechanisms ◽

Hippocampal Slices ◽

Spine Density ◽

Male And Female ◽

Dendritic Spine Density ◽

Male And Female Rats ◽

Rapid Modulation

Although the potent estrogen, 17β‎-estradiol (E2), has long been known to regulate the hippocampal dendritic spine density and synaptic plasticity, the molecular mechanisms through which it does so are less well understood. This chapter discusses the rapid modulation of hippocampal dendritic spine density and synaptic plasticity in male and female rats, with particular attention to studies in hippocampal slices from male rats. Among the mechanisms described are the roles of specific cell-signaling kinases and estrogen receptors in mediating the effects of E2 and progesterone on hippocampal neurons. In addition, dynamic changes of spine structures over time and sex differences in spine regulation are also considered. Finally, the chapter ends by discussing the importance of local hippocampal synthesis of E2 and androgens to hippocampal spine morphology and plasticity.

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Hormetic-Like Effects of L-Homocysteine on Synaptic Structure, Function, and Aβ Aggregation

Pharmaceuticals ◽

10.3390/ph13020024 ◽

2020 ◽

Vol 13 (2) ◽

pp. 24 ◽

Cited By ~ 2

Author(s):

Carla Montecinos-Oliva ◽

Macarena S. Arrázola ◽

Claudia Jara ◽

Cheril Tapia-Rojas ◽

Nibaldo C. Inestrosa

Keyword(s):

Oxidative Stress ◽

Risk Factor ◽

Hippocampal Slices ◽

The Elderly ◽

Long Term Potentiation ◽

Synaptic Activity ◽

Synaptic Proteins ◽

Protein Levels ◽

High Concentrations

Alzheimer’s Disease (AD) is the primary cause of dementia among the elderly population. Elevated plasma levels of homocysteine (HCy), an amino acid derived from methionine metabolism, are considered a risk factor and biomarker of AD and other types of dementia. An increase in HCy is mostly a consequence of high methionine and/or low vitamin B intake in the diet. Here, we studied the effects of physiological and pathophysiological HCy concentrations on oxidative stress, synaptic protein levels, and synaptic activity in mice hippocampal slices. We also studied the in vitro effects of HCy on the aggregation kinetics of Aβ40. We found that physiological cerebrospinal concentrations of HCy (0.5 µM) induce an increase in synaptic proteins, whereas higher doses of HCy (30–100 µM) decrease their levels, thereby increasing oxidative stress and causing excitatory transmission hyperactivity, which are all considered to be neurotoxic effects. We also observed that normal cerebrospinal concentrations of HCy slow the aggregation kinetic of Aβ40, whereas high concentrations accelerate its aggregation. Finally, we studied the effects of HCy and HCy + Aβ42 over long-term potentiation. Altogether, by studying an ample range of effects under different HCy concentrations, we report, for the first time, that HCy can exert beneficial or toxic effects over neurons, evidencing a hormetic-like effect. Therefore, we further encourage the use of HCy as a biomarker and modifiable risk factor with therapeutic use against AD and other types of dementia.

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Activation of Voltage‐Gated Sodium Channels with Brevetoxin‐2 (PbTx‐2) Increases Dendritic Spine Density in Murine Organotypic Hippocampal Slice Culture

The FASEB Journal ◽

10.1096/fasebj.29.1_supplement.1021.2 ◽

2015 ◽

Vol 29 (S1) ◽

Author(s):

Dina Gomez ◽

Thomas Murray

Keyword(s):

Sodium Channels ◽

Dendritic Spine ◽

Hippocampal Slice ◽

Slice Culture ◽

Spine Density ◽

Organotypic Hippocampal Slice Culture ◽

Voltage Gated ◽

Hippocampal Slice Culture ◽

Dendritic Spine Density ◽

Voltage Gated Sodium Channels

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Simultaneous analysis of dendritic spine density, morphology and excitatory glutamate receptors during neuron maturation in vitro by quantitative immunocytochemistry

Journal of Neuroscience Methods ◽

10.1016/j.jneumeth.2012.04.003 ◽

2012 ◽

Vol 207 (2) ◽

pp. 137-147 ◽

Cited By ~ 12

Author(s):

Evelyn Nwabuisi-Heath ◽

Mary Jo LaDu ◽

Chunjiang Yu

Keyword(s):

Glutamate Receptors ◽

Dendritic Spine ◽

Simultaneous Analysis ◽

Spine Density ◽

Quantitative Immunocytochemistry ◽

Dendritic Spine Density ◽

Maturation In Vitro

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Enhanced synaptic properties of the prefrontal cortex and hippocampus after learning a spatial working memory task in adult male mice

10.1101/339432 ◽

2018 ◽

Cited By ~ 1

Author(s):

Vasiliki Stavroulaki ◽

Vasileios Ioakeimidis ◽

Xanthippi Konstantoudaki ◽

Kyriaki Sidiropoulou

Keyword(s):

Working Memory ◽

Prefrontal Cortex ◽

Dendritic Spine ◽

Memory Task ◽

Long Term Potentiation ◽

Learning Task ◽

Spine Density ◽

Dendritic Spine Density ◽

Term Potentiation

AbstractWorking memory (WM) is the ability to hold on-line and manipulate information. The prefrontal cortex (PFC) is a key brain region involved in WM, while the hippocampus is also involved, particularly, in spatial WM. Although several studies have investigated the neuronal substrates of WM in trained animals, the effects and the mechanisms underlying learning WM tasks have not been explored. In our study, we investigated the effects of learning WM tasks in mice on the function of PFC and hippocampus, by training mice in the delayed alternation task for 9 days (adaptive group). This group was compared to naïve mice that stayed in their homecage (naïve) and mice trained in the alternation procedure only (non-adaptive). Following training, a cohort of mice (Experiment A) was tested in the left-right discrimination task and the reversal learning task, while another cohort (Experiment B) was tested in the attention set- shifting task (AST). The adaptive group performed significantly better in the reversal learning task (Experiment A) and AST (Experiment B), compared to non-adaptive and naïve groups. At the end of the behavioral experiments in Experiment A, field excitatory post-synaptic potential (fEPSP) recordings were performed in PFC and hippocampal brain slices. The adaptive group had enhanced the long-term potentiation (LTP) in the PFC, compared to the other groups. In the hippocampus, both the adaptive and the non-adaptive groups exhibited increased fEPSP compared to the naive group, but no differences in LTP. In Experiment B, the dendritic spine density was measured, which, in the PFC, was found increased in the adaptive group, compared to the non-adaptive and naive groups. In the hippocampus, there was an increase in mature dendritic spine density in the adaptive group, compared to the other two groups. Our results indicate a role for long-term potentiation and dendritic spine density in learning WM tasks.Significance statementWorking memory (WM) allows for transient storage and manipulation of information and has a central role in cognition. While a great number of research studies have investigated the mechanisms underlying the ‘memory’ part of WM in well-trained animals, the mechanisms that underlie learning WM tasks are not known. Studies have indicated that learning a WM tasks alters and enhances neuronal firing during the delay period, suggesting that long-term plasticity mechanisms could be involved. Our results in this study suggest that learning a working memory task primarily increases long-term potentiation and dendritic spine density in the prefrontal cortex, providing evidence for a role of long-term plasticity processes in learning working memory tasks. Furthermore, learning working memory tasks enhances cognitive flexibility.

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