The Transcription Factor Cux1 Regulates Dendritic Morphology of Cortical Pyramidal Neurons

Previous studies using the Golgi technique have demonstrated alterations in the dendritic morphology of pyramidal neurons of the cerebral cortex of mice inoculated with the rabies virus. However, knowledge about the fine structure of dendrites in rabies infection is scarce. This work had the aim of studying the ultrastructure of dendrites in cortical pyramidal neurons of rabies-infected mice. Mice were inoculated intramuscularly with a street rabies virus of canine origin. The animals that showed an advanced stage of disease were fixed by perfusion with glutaraldehyde and paraformaldehyde. Brains were removed and cut on a vibratome to obtain coronal slices of 200 micrometers of thickness. Vibratome slices were subjected to the following treatment: postfixation, dehydration, embedding in epoxy resin and polymerization between glass slides. Ultrathin sections of oriented tissue fragments from the cerebral cortex were obtained and observed under electron microscope. The most significant ultrastructural findings were located within distal dendrites of cortical pyramidal neurons: loss of mitochondria, disorganization and loss of microtubules, formation of vacuoles interrupting the continuity of the cytoplasm and formation of myelin-like figures. These strange myelin figures, which apparently had not been reported in previous studies of rabies, were the most noticeable ultrastructural feature. They also differ from the best known myelin figures formed by concentric lamellae. The possible origin of these myelin figures as result of mitochondrial degeneration is discussed.

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Unusual ultrastructural findings in dendrites of pyramidal neurons in the cerebral cortex of rabies-infected mice

10.7287/peerj.preprints.847 ◽

2015 ◽

Author(s):

Orlando Torres-Fernández ◽

Jeison Monroy-Gómez ◽

Ladys E Sarmiento

Keyword(s):

Cerebral Cortex ◽

Rabies Virus ◽

Pyramidal Neurons ◽

Ultrastructural Feature ◽

Dendritic Morphology ◽

Glass Slides ◽

Cortical Pyramidal Neurons ◽

Golgi Technique ◽

Ultrastructural Findings ◽

Myelin Figures

Previous studies using the Golgi technique have demonstrated alterations in the dendritic morphology of pyramidal neurons of the cerebral cortex of mice inoculated with the rabies virus. However, knowledge about the fine structure of dendrites in rabies infection is scarce. This work had the aim of studying the ultrastructure of dendrites in cortical pyramidal neurons of rabies-infected mice. Mice were inoculated intramuscularly with a street rabies virus of canine origin. The animals that showed an advanced stage of disease were fixed by perfusion with glutaraldehyde and paraformaldehyde. Brains were removed and cut on a vibratome to obtain coronal slices of 200 micrometers of thickness. Vibratome slices were subjected to the following treatment: postfixation, dehydration, embedding in epoxy resin and polymerization between glass slides. Ultrathin sections of oriented tissue fragments from the cerebral cortex were obtained and observed under electron microscope. The most significant ultrastructural findings were located within distal dendrites of cortical pyramidal neurons: loss of mitochondria, disorganization and loss of microtubules, formation of vacuoles interrupting the continuity of the cytoplasm and formation of myelin-like figures. These strange myelin figures, which apparently had not been reported in previous studies of rabies, were the most noticeable ultrastructural feature. They also differ from the best known myelin figures formed by concentric lamellae. The possible origin of these myelin figures as result of mitochondrial degeneration is discussed.

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Faculty Opinions recommendation of Phosphorylation of Neurogenin2 specifies the migration properties and the dendritic morphology of pyramidal neurons in the neocortex.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1028430.342210 ◽

2005 ◽

Author(s):

Susan K McConnell

Keyword(s):

Pyramidal Neurons ◽

Dendritic Morphology

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Faculty Opinions recommendation of Direct Intracellular Signaling by the Carboxy terminus of NMDA Receptor GluN2 Subunits Regulates Dendritic Morphology in Hippocampal CA1 Pyramidal Neurons.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.734490840.793564301 ◽

2019 ◽

Author(s):

Giles Hardingham

Keyword(s):

Nmda Receptor ◽

Intracellular Signaling ◽

Pyramidal Neurons ◽

Dendritic Morphology ◽

Carboxy Terminus ◽

Ca1 Pyramidal Neurons ◽

Hippocampal Ca1

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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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