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.

scholarly journals Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo

2021 ◽  
Author(s):  
Ling-Xiao Shao ◽  
Clara Liao ◽  
Ian Gregg ◽  
Neil K. Savalia ◽  
Kristina Delagarza ◽  
...  
Keyword(s):  
Single Dose ◽  
Frontal Cortex ◽  
Dendritic Spines ◽  
Pyramidal Neurons ◽  
Therapeutic Potential ◽  
Structural Plasticity ◽  
Head Width ◽  
Spine Density ◽  
Synaptic Remodeling

AbstractPsilocybin is a serotonergic psychedelic with untapped therapeutic potential. Here we chronically imaged apical dendritic spines of layer 5 pyramidal neurons in mouse medial frontal cortex. We found that a single dose of psilocybin led to ∼10% increases in spine density and spine head width. Synaptic remodeling occurred quickly within 24 hours and was persistent 1 month later. The results demonstrate structural plasticity that may underpin psilocybin’s long-lasting beneficial actions.

scholarly journals Hippocampal CA1 Pyramidal Neurons ofMecp2Mutant Mice Show a Dendritic Spine Phenotype Only in the Presymptomatic Stage

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Christopher A. Chapleau ◽  
Elena Maria Boggio ◽  
Gaston Calfa ◽  
Alan K. Percy ◽  
Maurizio Giustetto ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Pyramidal Neurons ◽  
Mutant Mice ◽  
Spine Density ◽  
Ca1 Pyramidal Neurons ◽  
Dendritic Spine Density ◽  
Presymptomatic Stage ◽  
Deficient Mice

Alterations in dendritic spines have been documented in numerous neurodevelopmental disorders, including Rett Syndrome (RTT). RTT, an X chromosome-linked disorder associated with mutations inMECP2, is the leading cause of intellectual disabilities in women. Neurons inMecp2-deficient mice show lower dendritic spine density in several brain regions. To better understand the role of MeCP2 on excitatory spine synapses, we analyzed dendritic spines of CA1 pyramidal neurons in the hippocampus ofMecp2tm1.1Jaemale mutant mice by either confocal microscopy or electron microscopy (EM). At postnatal-day 7 (P7), well before the onset of RTT-like symptoms, CA1 pyramidal neurons from mutant mice showed lower dendritic spine density than those from wildtype littermates. On the other hand, at P15 or later showing characteristic RTT-like symptoms, dendritic spine density did not differ between mutant and wildtype neurons. Consistently, stereological analyses at the EM level revealed similar densities of asymmetric spine synapses in CA1stratum radiatumof symptomatic mutant and wildtype littermates. These results raise caution regarding the use of dendritic spine density in hippocampal neurons as a phenotypic endpoint for the evaluation of therapeutic interventions in symptomaticMecp2-deficient mice. However, they underscore the potential role of MeCP2 in the maintenance of excitatory spine synapses.

scholarly journals Leptin Induces Hippocampal Synaptogenesis via CREB-Regulated MicroRNA-132 Suppression of p250GAP

2014 ◽  
Vol 28 (7) ◽  
pp. 1073-1087 ◽  
Author(s):  
Matasha Dhar ◽  
Mingyan Zhu ◽  
Soren Impey ◽  
Talley J. Lambert ◽  
Tyler Bland ◽  
...  
Keyword(s):  
Emotional Disorders ◽  
Dendritic Spine ◽  
Leptin Receptor ◽  
Pyramidal Neurons ◽  
Camp Response Element Binding ◽  
Spine Density ◽  
Creb Phosphorylation ◽  
Spine Formation ◽  
Hippocampal Synaptogenesis

Leptin acts in the hippocampus to enhance cognition and reduce depression and anxiety. Cognitive and emotional disorders are associated with abnormal hippocampal dendritic spine formation and synaptogenesis. Although leptin has been shown to induce synaptogenesis in the hypothalamus, its effects on hippocampal synaptogenesis and the mechanism(s) involved are not well understood. Here we show that leptin receptors (LepRs) are critical for hippocampal dendritic spine formation in vivo because db/db mice lacking the long form of the leptin receptor (LepRb) have reduced spine density on CA1 and CA3 neurons. Leptin promotes the formation of mature spines and functional glutamate synapses on hippocampal pyramidal neurons in both dissociated and slice cultures. These effects are blocked by short hairpin RNAs specifically targeting the LepRb and are absent in cultures from db/db mice. Activation of the LepR leads to cAMP response element–binding protein (CREB) phosphorylation and initiation of CREB-dependent transcription via the MAPK kinase/Erk pathway. Furthermore, both Mek/Erk and CREB activation are required for leptin-induced synaptogenesis. Leptin also increases expression of microRNA-132 (miR132), a well-known CREB target, which is also required for leptin-induced synaptogenesis. Last, leptin suppresses the expression of p250GAP, a miR132 target, and this suppression is obligatory for leptin's effects as is the downstream target of p250GAP, Rac1. LepRs appear to be critical in vivo as db/db mice have lowered hippocampal miR132 levels and elevated p250GAP expression. In conclusion, we identify a novel signaling pathway by which leptin increases synaptogenesis through inducing CREB transcription and increasing microRNA-mediated suppression of p250GAP activity, thus removing a known inhibitor of Rac1-stimulated synaptogenesis.

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 Lack of change in CA1 dendritic spine density or clustering in rats following training on a radial-arm maze task

2020 ◽  
Vol 5 ◽  
pp. 68
Author(s):  
Emma Craig ◽  
Christopher M. Dillingham ◽  
Michal M. Milczarek ◽  
Heather M. Phillips ◽  
Moira Davies ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Pyramidal Neurons ◽  
Memory Load ◽  
Spatial Location ◽  
Memory Formation ◽  
Spatial Task ◽  
Radial Arm Maze ◽  
Nearest Neighbour ◽  
Spine Density ◽  
Ca1 Region

Background: Neuronal plasticity is thought to underlie learning and memory formation. The density of dendritic spines in the CA1 region of the hippocampus has been repeatedly linked to mnemonic processes. Both the number and spatial location of the spines, in terms of proximity to nearest neighbour, have been implicated in memory formation. To examine how spatial training impacts synaptic structure in the hippocampus, Lister-Hooded rats were trained on a hippocampal-dependent spatial task in the radial-arm maze.  Methods: One group of rats were trained on a hippocampal-dependent spatial task in the radial arm maze. Two further control groups were included: a yoked group which received the same sensorimotor stimulation in the radial-maze but without a memory load, and home-cage controls. At the end of behavioural training, the brains underwent Golgi staining. Spines on CA1 pyramidal neuron dendrites were imaged and quantitatively assessed to provide measures of density and distance from nearest neighbour.  Results: There was no difference across behavioural groups either in terms of spine density or in the clustering of dendritic spines. Conclusions: Spatial learning is not always accompanied by changes in either the density or clustering of dendritic spines on the basal arbour of CA1 pyramidal neurons when assessed using Golgi imaging.

scholarly journals Chronic 2P-STED imaging reveals high turnover of dendritic spines in the hippocampus in vivo

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Thomas Pfeiffer ◽  
Stefanie Poll ◽  
Stephane Bancelin ◽  
Julie Angibaud ◽  
VVG Krishna Inavalli ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Super Resolution ◽  
Mammalian Brain ◽  
Spine Density ◽  
Behavioral Experiments ◽  
High Turnover ◽  
Synaptic Circuits ◽  
Working Distance ◽  
High Level

Rewiring neural circuits by the formation and elimination of synapses is thought to be a key cellular mechanism of learning and memory in the mammalian brain. Dendritic spines are the postsynaptic structural component of excitatory synapses, and their experience-dependent plasticity has been extensively studied in mouse superficial cortex using two-photon microscopy in vivo. By contrast, very little is known about spine plasticity in the hippocampus, which is the archetypical memory center of the brain, mostly because it is difficult to visualize dendritic spines in this deeply embedded structure with sufficient spatial resolution. We developed chronic 2P-STED microscopy in mouse hippocampus, using a ‘hippocampal window’ based on resection of cortical tissue and a long working distance objective for optical access. We observed a two-fold higher spine density than previous studies and measured a spine turnover of ~40% within 4 days, which depended on spine size. We thus provide direct evidence for a high level of structural rewiring of synaptic circuits and new insights into the structure-dynamics relationship of hippocampal spines. Having established chronic super-resolution microscopy in the hippocampus in vivo, our study enables longitudinal and correlative analyses of nanoscale neuroanatomical structures with genetic, molecular and behavioral experiments.

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