scholarly journals Conditional deletion of ROCK2 induces anxiety-like behaviors and alters dendritic spine density and morphology on CA1 pyramidal neurons

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Audrey J. Weber ◽  
Ashley B. Adamson ◽  
Kelsey M. Greathouse ◽  
Julia P. Andrade ◽  
Cameron D. Freeman ◽  
...  
Keyword(s):  
Dendritic Spine ◽  
Basolateral Amygdala ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Spine Density ◽  
Control Of Gene Expression ◽  
Spine Morphology ◽  
Dendritic Spine Morphology ◽  
Morphometry Analysis ◽  
Apical Dendrites

AbstractRho-associated kinase isoform 2 (ROCK2) is an attractive drug target for several neurologic disorders. A critical barrier to ROCK2-based research and therapeutics is the lack of a mouse model that enables investigation of ROCK2 with spatial and temporal control of gene expression. To overcome this, we generated ROCK2fl/fl mice. Mice expressing Cre recombinase in forebrain excitatory neurons (CaMKII-Cre) were crossed with ROCK2fl/fl mice (Cre/ROCK2fl/fl), and the contribution of ROCK2 in behavior as well as dendritic spine morphology in the hippocampus, medial prefrontal cortex (mPFC), and basolateral amygdala (BLA) was examined. Cre/ROCK2fl/fl mice spent reduced time in the open arms of the elevated plus maze and increased time in the dark of the light–dark box test compared to littermate controls. These results indicated that Cre/ROCK2fl/fl mice exhibited anxiety-like behaviors. To examine dendritic spine morphology, individual pyramidal neurons in CA1 hippocampus, mPFC, and the BLA were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and neuronal 3D reconstructions for morphometry analysis. In dorsal CA1, Cre/ROCK2fl/fl mice displayed significantly increased thin spine density on basal dendrites and reduced mean spine head volume across all spine types on apical dendrites. In ventral CA1, Cre/ROCK2fl/fl mice exhibited significantly increased spine length on apical dendrites. Spine density and morphology were comparable in the mPFC and BLA between both genotypes. These findings suggest that neuronal ROCK2 mediates spine density and morphology in a compartmentalized manner among CA1 pyramidal cells, and that in the absence of ROCK2 these mechanisms may contribute to anxiety-like behaviors.

scholarly journals Impact of JNK and Its Substrates on Dendritic Spine Morphology

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 440 ◽  
Author(s):  
Emilia Komulainen ◽  
Artemis Varidaki ◽  
Natalia Kulesskaya ◽  
Hasan Mohammad ◽  
Christel Sourander ◽  
...  
Keyword(s):  
Dendritic Spine ◽  
Pyramidal Neurons ◽  
Lucifer Yellow ◽  
Dendrite Morphology ◽  
Spine Morphology ◽  
Kinase Substrate ◽  
Basal Dendrites ◽  
Dendritic Spine Morphology ◽  
Mushroom Spines

The protein kinase JNK1 exhibits high activity in the developing brain, where it regulates dendrite morphology through the phosphorylation of cytoskeletal regulatory proteins. JNK1 also phosphorylates dendritic spine proteins, and Jnk1-/- mice display a long-term depression deficit. Whether JNK1 or other JNKs regulate spine morphology is thus of interest. Here, we characterize dendritic spine morphology in hippocampus of mice lacking Jnk1-/- using Lucifer yellow labelling. We find that mushroom spines decrease and thin spines increase in apical dendrites of CA3 pyramidal neurons with no spine changes in basal dendrites or in CA1. Consistent with this spine deficit, Jnk1-/- mice display impaired acquisition learning in the Morris water maze. In hippocampal cultures, we show that cytosolic but not nuclear JNK, regulates spine morphology and expression of phosphomimicry variants of JNK substrates doublecortin (DCX) or myristoylated alanine-rich C kinase substrate-like protein-1 (MARCKSL1), rescue mushroom, thin, and stubby spines differentially. These data suggest that physiologically active JNK controls the equilibrium between mushroom, thin, and stubby spines via phosphorylation of distinct substrates.

Influence of aging and neurodegeneration on dendritic spine morphology

2011 ◽  
Vol 2 (1) ◽  
Author(s):  
Erik Bloss ◽  
John Morrison ◽  
Patrick Hof ◽  
Dara Dickstein
Keyword(s):  
Animal Models ◽  
Dendritic Spine ◽  
Transgenic Animal ◽  
Spine Density ◽  
Spine Morphology ◽  
Dendritic Spine Morphology ◽  
Transgenic Animal Models ◽  
Drug Treatments ◽  
Synaptic Changes ◽  
Spine Function

AbstractIn neuronal circuits, excitatory synaptic transmission predominantly occurs at postsynaptic protrusions called dendritic spines. Spines are highly plastic structures capable of formation, enlargement, shrinkage, and elimination over time. Individual spine morphology is widely variable, and evidence suggests these differences in morphology are relevant to spine function. Recent reports provide evidence that spine structural plasticity underlies functional synaptic changes, including those seen in animal models of learning and memory plasticity. Conversely, impairments in cognitive functions, such as those commonly seen in aging, have recently been linked to and correlated with alterations in spine density and morphology. In addition, dendritic spine density and morphology also appear to be altered in various transgenic animal models of neurodegenerative diseases. Ultimately, an understanding of the synaptic basis of age- and disease-related cognitive impairments may lead to the development of drug treatments that can restore or protect synaptic profiles in neural circuits that mediate cognition.

scholarly journals Hyperforin modulates dendritic spine morphology in hippocampal pyramidal neurons by activating Ca2+-permeable TRPC6 channels

Hippocampus ◽  
2012 ◽  
Vol 23 (1) ◽  
pp. 40-52 ◽  
Author(s):  
Kristina Leuner ◽  
Wei Li ◽  
Michelle D. Amaral ◽  
Stephanie Rudolph ◽  
Gaston Calfa ◽  
...  
Keyword(s):  
Dendritic Spine ◽  
Pyramidal Neurons ◽  
Spine Morphology ◽  
Hippocampal Pyramidal Neurons ◽  
Dendritic Spine Morphology

Dendritic Spine Density of Pyramidal Neurons in Field CA1 of the Hippocampus Decreases due to Chronic Tryptophan Restriction

1998 ◽  
Vol 1 (3) ◽  
pp. 237-242 ◽  
Author(s):  
M.I. Pérez-Vega ◽  
G. Barajas-López ◽  
A.R. del Angel-Meza ◽  
I. González-Burgos ◽  
A. Feria-Velasco
Keyword(s):  
Dendritic Spine ◽  
Pyramidal Neurons ◽  
Spine Density ◽  
Dendritic Spine Density ◽  
Field Ca1

scholarly journals Distal axotomy enhances retrograde presynaptic excitability onto injured pyramidal neurons via trans-synaptic signaling

2016 ◽  
Author(s):  
Tharkika Nagendran ◽  
Rylan S. Larsen ◽  
Rebecca L. Bigler ◽  
Shawn B. Frost ◽  
Benjamin D. Philpot ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Pyramidal Neurons ◽  
Spine Density ◽  
Axon Injury ◽  
Synaptic Remodeling ◽  
Nerve Tracts ◽  
Specific Increase ◽  
Microfluidic Chambers

AbstractInjury of CNS nerve tracts remodels circuitry through dendritic spine loss and hyper-excitability, thus influencing recovery. Due to the complexity of the CNS, a mechanistic understanding of injury-induced synaptic remodeling remains unclear. Using microfluidic chambers to separate and injure distal axons, we show that axotomy causes retrograde dendritic spine loss at directly injured pyramidal neurons followed by retrograde presynaptic hyper-excitability. These remodeling events require activity at the site of injury, axon-to-soma signaling, and transcription. Similarly, directly injured corticospinal neurons in vivo also exhibit a specific increase in spiking following axon injury. Axotomy-induced hyper-excitability of cultured neurons coincides with elimination of inhibitory inputs onto injured neurons, including those formed onto dendritic spines. Netrin-1 downregulation occurs following axon injury and exogenous netrin-1 applied after injury normalizes spine density, presynaptic excitability, and inhibitory inputs at injured neurons. Our findings show that intrinsic signaling within damaged neurons regulates synaptic remodeling and involves netrin-1 signaling.

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