Testosterone modulation of dendritic spines of somatosensory cortical pyramidal neurons

AbstractWe present the first-ever detailed models of pyramidal cells from human neocortex, including models on their excitatory synapses, dendritic spines, dendritic NMDA- and somatic/axonal- Na+ spikes that provided new insights into signal processing and computational capabilities of these principal cells. Six human layer 2 and layer 3 pyramidal cells (HL2/L3 PCs) were modeled, integrating detailed anatomical and physiological data from both fresh and post mortem tissues from human temporal cortex. The models predicted particularly large AMPA- and NMDA- conductances per synaptic contact (0.88 nS and 1.31nS, respectively) and a steep dependence of the NMDA-conductance on voltage. These estimates were based on intracellular recordings from synaptically-connected HL2/L3 pairs, combined with extra-cellular current injections and use of synaptic blockers. A large dataset of high-resolution reconstructed HL2/L3 dendritic spines provided estimates for the EPSPs at the spine head (12.7 ± 4.6 mV), spine base (9.7 ± 5.0 mV) and soma (0.3 ± 0.1 mV), and for the spine neck resistance (50 – 80 MΩ). Matching the shape and firing pattern of experimental somatic Na+-spikes provided estimates for the density of the somatic/axonal excitable membrane ion channels, predicting that 134 ± 28 simultaneously activated HL2/L3- HL2/L3 synapses are required for generating (with 50% probability) a somatic Na+ spike. Dendritic NMDA spikes were triggered in the model when 20 ± 10 excitatory spinous synapses were simultaneously activated on individual dendritic branches. The particularly large number of basal dendrites in HL2/L3 PCs and the distinctive cable elongation of their terminals imply that ~25 NMDA- spikes could be generated independently and simultaneously in these cells, as compared to ~14 in L2/3 PCs from the rat temporal cortex. These multi-sites nonlinear signals, together with the large (~30,000) excitatory synapses/cell, equip human L2/L3 PCs with enhanced computational capabilities. Our study provides the most comprehensive model of any human neuron to-date demonstrating the biophysical and computational distinctiveness of human cortical neurons.

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Reproductive experience modified dendritic spines on cortical pyramidal neurons to enhance sensory perception and spatial learning in rats

Experimental Animals ◽

10.1538/expanim.16-0061 ◽

2017 ◽

Vol 66 (1) ◽

pp. 61-74 ◽

Cited By ~ 4

Author(s):

Jeng-Rung Chen ◽

Seh Hong Lim ◽

Sin-Cun Chung ◽

Yee-Fun Lee ◽

Yueh-Jan Wang ◽

...

Keyword(s):

Spatial Learning ◽

Dendritic Spines ◽

Pyramidal Neurons ◽

Sensory Perception ◽

Reproductive Experience ◽

Cortical Pyramidal Neurons

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Laminar Differences in the Targeting of Dendritic Spines by Cortical Pyramidal Neurons and Interneurons in Human Dorsolateral Prefrontal Cortex

Neuroscience ◽

10.1016/j.neuroscience.2020.10.022 ◽

2021 ◽

Vol 452 ◽

pp. 181-191

Author(s):

Jill R. Glausier ◽

Dibyadeep Datta ◽

Kenneth N. Fish ◽

Daniel W. Chung ◽

Darlene S. Melchitzky ◽

...

Keyword(s):

Prefrontal Cortex ◽

Dendritic Spines ◽

Dorsolateral Prefrontal Cortex ◽

Pyramidal Neurons ◽

Dorsolateral Prefrontal ◽

Cortical Pyramidal Neurons

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The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer’s disease

Brain ◽

10.1093/brain/awt088 ◽

2013 ◽

Vol 136 (6) ◽

pp. 1913-1928 ◽

Cited By ~ 73

Author(s):

Paula Merino-Serrais ◽

Ruth Benavides-Piccione ◽

Lidia Blazquez-Llorca ◽

Asta Kastanauskaite ◽

Alberto Rábano ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Dendritic Spines ◽

Pyramidal Neurons ◽

Cortical Pyramidal Neurons

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EPSPs Measured in Proximal Dendritic Spines of Cortical Pyramidal Neurons

eNeuro ◽

10.1523/eneuro.0050-15.2016 ◽

2016 ◽

Vol 3 (2) ◽

pp. ENEURO.0050-15.2016 ◽

Cited By ~ 20

Author(s):

Corey D. Acker ◽

Erika Hoyos ◽

Leslie M. Loew

Keyword(s):

Dendritic Spines ◽

Pyramidal Neurons ◽

Cortical Pyramidal Neurons

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Two-Photon Microscopy of Single Molecules

Microscopy and Microanalysis ◽

10.1017/s1431927600036515 ◽

2000 ◽

Vol 6 (S2) ◽

pp. 804-805

Author(s):

R. Yuste ◽

A. Majewska ◽

K. Holthoff ◽

K. Holthoff

Keyword(s):

Dendritic Spines ◽

Pyramidal Neurons ◽

Calcium Influx ◽

Pyramidal Cells ◽

Scattering Media ◽

Decay Kinetics ◽

Two Photon ◽

Photon Excitation ◽

Cortical Pyramidal Neurons ◽

Two Photon Excitation

Two-photon excitation has enabled investigators to image living cells in highly scattering media like the central nervous system (1). We have used a custom-built two-photon microscope to image dendritic spines from living cortical pyramidal neurons. Pyramidal cells form the majority of the neuron in the mammalian cortex and they receive practically all their synaptic contacts through dendritic spines. Dendritic spines are small (<1 μm diameter) appendages that have been practically inaccessible to physiological measurements until the application of two-photon excitation to their study (2). We have concentrated in two questions:A- Calcium compartmentalization of spines: Mechanisms of calcium decay kinetics.Dendritic spines can compartmentalize calcium (2). Although the mechanisms of calcium influx into spines have been explored (3), it is unknown what determines the calcium decay kinetics in spines. We investigate calcium dynamics in spines from rat CA1 pyramidal neurons in slices.

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Temporal Regulation of Dendritic Spines Through NrCAM-Semaphorin3F Receptor Signaling in Developing Cortical Pyramidal Neurons

Cerebral Cortex ◽

10.1093/cercor/bhy004 ◽

2018 ◽

Vol 29 (3) ◽

pp. 963-977 ◽

Cited By ~ 9

Author(s):

Vishwa Mohan ◽

Chelsea S Sullivan ◽

Jiami Guo ◽

Sarah D Wade ◽

Samarpan Majumder ◽

...

Keyword(s):

Dendritic Spines ◽

Pyramidal Neurons ◽

Receptor Signaling ◽

Temporal Regulation ◽

Cortical Pyramidal Neurons

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Semaphorin3F Drives Dendritic Spine Pruning through Rho-GTPase Signaling

10.1101/2021.03.05.433425 ◽

2021 ◽

Author(s):

Bryce W. Duncan ◽

Vishwa Mohan ◽

Sarah D. Wade ◽

Young Truong ◽

Alexander Kampov-Polevoi ◽

...

Keyword(s):

Dendritic Spines ◽

Cortical Neurons ◽

Pyramidal Neurons ◽

Rho Gtpase ◽

Myosin Ii ◽

Actin Remodeling ◽

Semaphorin 3F ◽

Cortical Pyramidal Neurons ◽

Insight Into ◽

Spine Pruning

Dendritic spines of cortical pyramidal neurons are initially overproduced then remodeled substantially in the adolescent brain to achieve appropriate excitatory balance in mature circuits. Here we investigated the molecular mechanism of developmental spine pruning by Semaphorin 3F (Sema3F) and its holoreceptor complex, which consists of immunoglobulin-class adhesion molecule NrCAM, Neuropilin-2 (Npn2), and PlexinA3 (PlexA3) signaling subunits. Structure-function studies of the NrCAM-Npn2 interface showed that NrCAM stabilizes binding between Npn2 and PlexA3 necessary for Sema3F-induced spine pruning. Using a mouse neuronal culture system, we identified a dual signaling pathway for Sema3F-induced pruning, which involves activation of Tiam1-Rac1-PAK1-3 -LIMK1/2-Cofilin1 and RhoA-ROCK1/2-Myosin II in dendritic spines. Inhibitors of actin remodeling impaired spine collapse in the cortical neurons. Elucidation of these pathways expands our understanding of critical events that sculpt neuronal networks and may provide insight into how interruptions to these pathways could lead to spine dysgenesis in diseases such as autism, bipolar disorder, and schizophrenia.

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Ectopic HCN4 expression drives mTOR-dependent epilepsy in mice

Science Translational Medicine ◽

10.1126/scitranslmed.abc1492 ◽

2020 ◽

Vol 12 (570) ◽

pp. eabc1492

Author(s):

Lawrence S. Hsieh ◽

John H. Wen ◽

Lena H. Nguyen ◽

Longbo Zhang ◽

Stephanie A. Getz ◽

...

Keyword(s):

Mouse Model ◽

Pyramidal Neurons ◽

Focal Cortical Dysplasia ◽

Repetitive Firing ◽

Intracellular Camp ◽

Main Role ◽

Channel Activity ◽

Mechanistic Target Of Rapamycin ◽

Cortical Pyramidal Neurons ◽

Causative Link

The causative link between focal cortical malformations (FCMs) and epilepsy is well accepted, especially among patients with focal cortical dysplasia type II (FCDII) and tuberous sclerosis complex (TSC). However, the mechanisms underlying seizures remain unclear. Using a mouse model of TSC- and FCDII-associated FCM, we showed that FCM neurons were responsible for seizure activity via their unexpected abnormal expression of the hyperpolarization-activated cyclic nucleotide–gated potassium channel isoform 4 (HCN4), which is normally not present in cortical pyramidal neurons after birth. Increasing intracellular cAMP concentrations, which preferentially affects HCN4 gating relative to the other isoforms, drove repetitive firing of FCM neurons but not control pyramidal neurons. Ectopic HCN4 expression was dependent on the mechanistic target of rapamycin (mTOR), preceded the onset of seizures, and was also found in diseased neurons in tissue resected from patients with TSC and FCDII. Last, blocking HCN4 channel activity in FCM neurons prevented epilepsy in the mouse model. These findings suggest that HCN4 play a main role in seizure and identify a cAMP-dependent seizure mechanism in TSC and FCDII. Furthermore, the unique expression of HCN4 exclusively in FCM neurons suggests that gene therapy targeting HCN4 might be effective in reducing seizures in FCDII or TSC.

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