Steady-state dynamics and experience-dependent plasticity of dendritic spines of layer 4/5a pyramidal neurons in somatosensory cortex

SUMMARYSpike-timing-dependent plasticity (STDP) has been extensively studied in cortical pyramidal neurons, however, the precise structural organization of excitatory inputs that supports STDP, as well as the structural, molecular and functional properties of dendritic spines during STDP remain unknown. Here we performed a spine STDP protocol using two-photon glutamate uncaging to mimic presynaptic glutamate release (pre) paired with somatically generated postsynaptic spikes (post). We found that the induction of STDP in single spines follows a classical Hebbian STDP rule, where pre-post pairings at timings that trigger LTP (t-LTP) produce shrinkage of the activated spine neck and a concomitant increase in its synaptic strength; and post-pre pairings that trigger LTD (t-LTD) decrease synaptic strength without affecting the activated spine shape. Furthermore, we tested whether the single spine-Hebbian STDP rule could be affected by the activation of neighboring (clustered) or distant (distributed) spines. Our results show that the induction of t-LTP in two clustered spines (<5 μm apart) enhances LTP through a mechanism dependent on local spine calcium accumulation and actin polymerization-dependent neck shrinkage, whereas t-LTD was disrupted by the activation of two clustered spines but recovered when spines were separated by >40 μm. These results indicate that synaptic cooperativity, induced by the co-activation of only two clustered spines, provides local dendritic depolarization and local calcium signals sufficient to disrupt t-LTD and extend the temporal window for the induction of t-LTP, leading to STDP only encompassing LTP.

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Experience-dependent plasticity of dendritic spines of layer 2/3 pyramidal neurons in the mouse cortex

Developmental Neurobiology ◽

10.1002/dneu.22313 ◽

2015 ◽

Vol 76 (3) ◽

pp. 277-286 ◽

Cited By ~ 39

Author(s):

Lei Ma ◽

Qian Qiao ◽

Jin-Wu Tsai ◽

Guang Yang ◽

Wei Li ◽

...

Keyword(s):

Dendritic Spines ◽

Pyramidal Neurons ◽

Dependent Plasticity ◽

Mouse Cortex ◽

Layer 2

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Unique properties of dually innervated dendritic spines in pyramidal neurons of the somatosensory cortex uncovered by 3D correlative light and electron microscopy

PLoS Biology ◽

10.1371/journal.pbio.3001375 ◽

2021 ◽

Vol 19 (8) ◽

pp. e3001375

Author(s):

Olivier Gemin ◽

Pablo Serna ◽

Joseph Zamith ◽

Nora Assendorp ◽

Matteo Fossati ◽

...

Keyword(s):

Electron Microscopy ◽

Somatosensory Cortex ◽

Dendritic Spines ◽

Computational Models ◽

Pyramidal Neurons ◽

Light And Electron Microscopy ◽

Inhibitory Synapses ◽

Dendritic Shaft ◽

Intact Brain ◽

The Impact

Pyramidal neurons (PNs) are covered by thousands of dendritic spines receiving excitatory synaptic inputs. The ultrastructure of dendritic spines shapes signal compartmentalization, but ultrastructural diversity is rarely taken into account in computational models of synaptic integration. Here, we developed a 3D correlative light–electron microscopy (3D-CLEM) approach allowing the analysis of specific populations of synapses in genetically defined neuronal types in intact brain circuits. We used it to reconstruct segments of basal dendrites of layer 2/3 PNs of adult mouse somatosensory cortex and quantify spine ultrastructural diversity. We found that 10% of spines were dually innervated and 38% of inhibitory synapses localized to spines. Using our morphometric data to constrain a model of synaptic signal compartmentalization, we assessed the impact of spinous versus dendritic shaft inhibition. Our results indicate that spinous inhibition is locally more efficient than shaft inhibition and that it can decouple voltage and calcium signaling, potentially impacting synaptic plasticity.

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Removal of a compressive mass causes a transient disruption of blood-brain barrier but a long-term recovery of spiny stellate neurons in the rat somatosensory cortex

Restorative Neurology and Neuroscience ◽

10.3233/rnn-201085 ◽

2021 ◽

pp. 1-17

Author(s):

Tzu-Yin Yeh ◽

Pei-Hsin Liu

Keyword(s):

Somatosensory Cortex ◽

Blood Brain Barrier ◽

Dendritic Spines ◽

Late Onset ◽

Brain Barrier ◽

Blood Brain ◽

Afferent Fibers ◽

Prolonged Recovery ◽

Rat Somatosensory Cortex

Background: In the cranial cavity, a space-occupying mass such as epidural hematoma usually leads to compression of brain. Removal of a large compressive mass under the cranial vault is critical to the patients. Objective: The purpose of this study was to examine whether and to what extent epidural decompression of the rat primary somatosensory cortex affects the underlying microvessels, spiny stellate neurons and their afferent fibers. Methods: Rats received epidural decompression with preceding 1-week compression by implantation of a bead. The thickness of cortex was measured using brain coronal sections. The permeability of blood-brain barrier (BBB) was assessed by Evans Blue and immunoglobulin G extravasation. The dendrites and dendritic spines of the spiny stellate neurons were revealed by Golgi— Cox staining and analyzed. In addition, the thalamocortical afferent (TCA) fibers in the cortex were illustrated using anterograde tracing and examined. Results: The cortex gradually regained its thickness over time and became comparable to the sham group at 3 days after decompression. Although the diameter of cortical microvessels were unaltered, a transient disruption of the BBB was observed at 6 hours and 1 day after decompression. Nevertheless, no brain edema was detected. In contrast, the dendrites and dendritic spines of the spiny stellate neurons and the TCA fibers were markedly restored from 2 weeks to 3 months after decompression. Conclusions: Epidural decompression caused a breakdown of the BBB, which was early-occurring and short-lasting. In contrast, epidural decompression facilitated a late-onset and prolonged recovery of the spiny stellate neurons and their afferent fibers.

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Loss of Calretinin in L5a impairs the formation of the barrel cortex leading to abnormal whisker-mediated behaviors

Molecular Brain ◽

10.1186/s13041-021-00775-w ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Mingzhao Su ◽

Junhua Liu ◽

Baocong Yu ◽

Kaixing Zhou ◽

Congli Sun ◽

...

Keyword(s):

Information Integration ◽

Pyramidal Neurons ◽

Barrel Cortex ◽

Sensory Information ◽

Membrane Excitability ◽

Novelty Preference ◽

Layer 4 ◽

Dendritic Complexity ◽

Cortex System

AbstractThe rodent whisker-barrel cortex system has been established as an ideal model for studying sensory information integration. The barrel cortex consists of barrel and septa columns that receive information input from the lemniscal and paralemniscal pathways, respectively. Layer 5a is involved in both barrel and septa circuits and play a key role in information integration. However, the role of layer 5a in the development of the barrel cortex remains unclear. Previously, we found that calretinin is dynamically expressed in layer 5a. In this study, we analyzed calretinin KO mice and found that the dendritic complexity and length of layer 5a pyramidal neurons were significantly decreased after calretinin ablation. The membrane excitability and excitatory synaptic transmission of layer 5a neurons were increased. Consequently, the organization of the barrels was impaired. Moreover, layer 4 spiny stellate cells were not able to properly gather, leading to abnormal formation of barrel walls as the ratio of barrel/septum size obviously decreased. Calretinin KO mice exhibited deficits in exploratory and whisker-associated tactile behaviors as well as social novelty preference. Our study expands our knowledge of layer 5a pyramidal neurons in the formation of barrel walls and deepens the understanding of the development of the whisker-barrel cortex system.

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Adolescent pruning and stabilization of dendritic spines on cortical layer 5 pyramidal neurons do not depend on gonadal hormones

Developmental Cognitive Neuroscience ◽

10.1016/j.dcn.2018.01.007 ◽

2018 ◽

Vol 30 ◽

pp. 100-107 ◽

Cited By ~ 7

Author(s):

Josiah R. Boivin ◽

David J. Piekarski ◽

A. Wren Thomas ◽

Linda Wilbrecht

Keyword(s):

Dendritic Spines ◽

Pyramidal Neurons ◽

Gonadal Hormones ◽

Cortical Layer

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Monosynaptic Connections between Pairs of L5A Pyramidal Neurons in Columns of Juvenile Rat Somatosensory Cortex

Cerebral Cortex ◽

10.1093/cercor/bhm074 ◽

2007 ◽

Vol 18 (2) ◽

pp. 397-406 ◽

Cited By ~ 52

Author(s):

A. Frick ◽

D. Feldmeyer ◽

M. Helmstaedter ◽

B. Sakmann

Keyword(s):

Somatosensory Cortex ◽

Pyramidal Neurons ◽

Rat Somatosensory Cortex

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

Wellcome Open Research ◽

10.12688/wellcomeopenres.15745.2 ◽

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.

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

10.1101/065391 ◽

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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