MeCP2 Mutation Results in Compartment-Specific Reductions in Dendritic Branching and Spine Density in Layer 5 Motor Cortical Neurons of YFP-H Mice

Cortical networks are characterized by sparse connectivity, with synapses found at only a subset of axo-dendritic contacts. Yet within these networks, neurons can exhibit high connection probabilities, suggesting that cell-intrinsic factors, not proximity, determine connectivity. Here, we identify ephrin-B3 (eB3) as a factor that determines synapse density by mediating a cell-cell competition that requires ephrin-B-EphB signaling. In a microisland culture system designed to isolate cell-cell competition, we find that eB3 determines winning and losing neurons in a contest for synapses. In a Mosaic Analysis with Double Markers (MADM) genetic mouse model system in vivo the relative levels of eB3 control spine density in layer 5 and 6 neurons. MADM cortical neurons in vitro reveal that eB3 controls synapse density independently of action potential-driven activity. Our findings illustrate a new class of competitive mechanism mediated by trans-synaptic organizing proteins which control the number of synapses neurons receive relative to neighboring neurons.

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Increased signaling by the autism-related Engrailed-2 protein enhances dendritic branching and spine density, alters synaptic structural matching, and exaggerates protein synthesis

PLoS ONE ◽

10.1371/journal.pone.0181350 ◽

2017 ◽

Vol 12 (8) ◽

pp. e0181350 ◽

Cited By ~ 7

Author(s):

Asma Soltani ◽

Solène Lebrun ◽

Gilles Carpentier ◽

Giulia Zunino ◽

Sandrine Chantepie ◽

...

Keyword(s):

Protein Synthesis ◽

Spine Density ◽

Dendritic Branching ◽

Structural Matching

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Early Sensory Loss Alters the Dendritic Branching and Spine Density of Supragranular Pyramidal Neurons in Rodent Primary Sensory Cortices

Frontiers in Neural Circuits ◽

10.3389/fncir.2019.00061 ◽

2019 ◽

Vol 13 ◽

Author(s):

Tamar Macharadze ◽

Eike Budinger ◽

Michael Brosch ◽

Henning Scheich ◽

Frank W. Ohl ◽

...

Keyword(s):

Pyramidal Neurons ◽

Sensory Loss ◽

Spine Density ◽

Dendritic Branching ◽

Sensory Cortices

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Hypothetical joint-related coordinate systems in which populations of motor cortical neurons code direction of voluntary arm movements

Neuroscience Letters ◽

10.1016/0304-3940(94)90493-6 ◽

1994 ◽

Vol 180 (2) ◽

pp. 83-86 ◽

Cited By ~ 9

Author(s):

Shoji Tanaka

Keyword(s):

Cortical Neurons ◽

Arm Movements ◽

Coordinate Systems ◽

Motor Cortical

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Computer Simulation of Post-Spike Facilitation in Spike-Triggered Averages of Rectified EMG

Journal of Neurophysiology ◽

10.1152/jn.1998.80.3.1391 ◽

1998 ◽

Vol 80 (3) ◽

pp. 1391-1406 ◽

Cited By ~ 41

Author(s):

S. N. Baker ◽

R. N. Lemon

Keyword(s):

Computer Simulation ◽

Action Potential ◽

Motor Unit ◽

Cortical Neurons ◽

Emg Activity ◽

Motor Unit Action Potential ◽

Cortical Cells ◽

Motor Unit Action ◽

Motor Cortical ◽

Unit Action

Baker, S. N. and R. N. Lemon. Computer simulation of post-spike facilitation in spike-triggered averages of rectified EMG. J. Neurophysiol. 80: 1391–1406, 1998. When the spikes of a motor cortical cell are used to compile a spike-triggered average (STA) of rectified electromyographic (EMG) activity, a post-spike facilitation (PSF) is sometimes seen. This is generally thought to be indicative of direct corticomotoneuronal (CM) connections. However, it has been claimed that a PSF could be caused by synchronization between CM and non-CM cells. This study investigates the generation of PSF using a computer model. A population of cortical cells was simulated, some of which made CM connections to a pool of 103 motoneurons. Motoneurons were simulated using a biophysically realistic model. A subpopulation of the cortical cells was synchronized together. After a motoneuron discharge, a motor unit action potential was generated; these were summed to produce an EMG output. Realistic values were used for the corticospinal and peripheral nerve conduction velocity distribution, for slowing of impulse conduction in CM terminal axons, and for the amount of cortical synchrony. STA of the rectified EMG from all cortical neurons showed PSF; however, these were qualitatively different for CM versus non-CM cells. Using an epoch analysis to determine reliability in a quantitative manner, it was shown that the onset latency of PSF did not distinguish the two classes of cells after 10,000 spikes because of high noise in the averages. The time of the PSF peak and the peak width at half-maximum (PWHM) could separate CM from synchrony effects. However, only PWHM was robust against changes in motor unit action-potential shape and duration and against changes in the width of cortical synchrony. The amplitude of PSF from a CM cell could be doubled by the presence of synchrony. It is proposed that, if a PSF has PWHM <7 ms, this reliably indicates that the trigger is a CM cell projecting to the muscle whose EMG is averaged. In an analysis of experimental data where macaque motor cortical cells facilitated hand and forearm muscle EMG, 74% of PSFs fulfilled this criterion. The PWHM criterion could be applied to other STA studies in which it is important to exclude the effects of synchrony.

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Picrotoxin blocks arousal-associated suppression caused by basal forebrain stimulation in cerebral motor cortical neurons of the rat

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)40479-4 ◽

1998 ◽

Vol 76 ◽

pp. 90

Author(s):

Miyuki Yokoyama ◽

Keiko Arai ◽

Tomokazu Oshima

Keyword(s):

Basal Forebrain ◽

Cortical Neurons ◽

Motor Cortical

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Reversal of Age-Related Neuronal Atrophy by α5-GABAA Receptor Positive Allosteric Modulation

Cerebral Cortex ◽

10.1093/cercor/bhaa310 ◽

2020 ◽

Author(s):

Thomas D Prevot ◽

Akiko Sumitomo ◽

Toshifumi Tomoda ◽

Daniel E Knutson ◽

Guanguan Li ◽

...

Keyword(s):

Working Memory ◽

Beneficial Effect ◽

Frontal Cortex ◽

Cortical Neurons ◽

Gaba A ◽

Age Related ◽

Dendritic Branching ◽

Old Mice ◽

Separate Cohort

Abstract Aging is associated with reduced brain volume, altered neural activity, and neuronal atrophy in cortical-like structures, comprising the frontal cortex and hippocampus, together contributing to cognitive impairments. Therapeutic efforts aimed at reversing these deficits have focused on excitatory or neurotrophic mechanisms, although recent findings show that reduced dendritic inhibition mediated by α5-subunit containing GABA-A receptors (α5-GABAA-Rs) occurs during aging and contributes to cognitive impairment. Here, we aimed to confirm the beneficial effect on working memory of augmenting α5-GABAA-R activity in old mice and tested its potential at reversing age-related neuronal atrophy. We show that GL-II-73, a novel ligand with positive allosteric modulatory activity at α5-GABAA-R (α5-PAM), increases dendritic branching complexity and spine numbers of cortical neurons in vitro. Using old mice, we confirm that α5-PAM reverses age-related working memory deficits and show that chronic treatment (3 months) significantly reverses age-related dendritic shrinkage and spine loss in frontal cortex and hippocampus. A subsequent 1-week treatment cessation (separate cohort) resulted in loss of efficacy on working memory but maintained morphological neurotrophic effects. Together, the results demonstrate the beneficial effect on working memory and neurotrophic efficacy of augmenting α5-GABAA-R function in old mice, suggesting symptomatic and disease-modifying potential in age-related brain disorders.

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