scholarly journals Transcriptomic evidence that von Economo neurons are regionally specialized extratelencephalic-projecting excitatory neurons

2019 ◽  
Author(s):  
Rebecca D Hodge ◽  
Jeremy A Miller ◽  
Mark Novotny ◽  
Brian E Kalmbach ◽  
Jonathan T Ting ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Temporal Cortex ◽  
Anterior Cingulate ◽  
Cell Cluster ◽  
Membrane Properties ◽  
Von Economo Neurons ◽  
Strong Homology ◽  
Excitatory Neurons ◽  
Distinctive Type ◽  
Cellular Phenotypes

Abstractvon Economo neurons (VENs) are bipolar, spindle-shaped neurons restricted to layer 5 of human frontoinsula and anterior cingulate cortex that appear to be selectively vulnerable to neuropsychiatric and neurodegenerative diseases, although little is known about other VEN cellular phenotypes. Single nucleus RNA-sequencing of frontoinsula layer 5 identified a transcriptomically-defined cell cluster that contained VENs, but also fork cells and a subset of pyramidal neurons. Cross-species alignment of this cell cluster with a well-annotated mouse classification shows strong homology to extratelencephalic (ET) excitatory neurons that project to subcerebral targets. This cluster also shows strong homology to a putative ET cluster in human temporal cortex, but with a strikingly specific regional signature. Together these results predict VENs are a regionally distinctive type of ET neuron, and we additionally describe the first patch clamp recordings of VENs from neurosurgically-resected tissue that show distinctive intrinsic membrane properties relative to neighboring pyramidal neurons.

scholarly journals Von Economo Neuron Pathology in Familial Dysautonomia: Quantitative Assessment and Possible Implications

2020 ◽  
Vol 79 (10) ◽  
pp. 1072-1083
Author(s):  
Sarah Jacot-Descombes ◽  
Neha Keshav ◽  
Carla Micaela Santos Brosch ◽  
Bridget Wicinski ◽  
Tahia Warda ◽  
...  
Keyword(s):  
Nervous System ◽  
Pyramidal Neurons ◽  
Repetitive Behavior ◽  
Familial Dysautonomia ◽  
Autism Spectrum ◽  
Anterior Cingulate ◽  
Emotional States ◽  
Functional Link ◽  
Von Economo Neurons ◽  
Fork Cells

Abstract Von Economo neurons (VENs) and fork cells are principally located in the anterior cingulate cortex (ACC) and the frontoinsular cortex (FI). Both of these regions integrate inputs from the autonomic nervous system (ANS) and are involved in decision-making and perception of the emotional states of self and others. Familial dysautonomia (FD) is an orphan disorder characterized by autonomic dysfunction and behavioral abnormalities including repetitive behavior and emotional rigidity, which are also seen in autism spectrum disorder. To understand a possible link between the ANS and the cortical regions implicated in emotion regulation we studied VENs and fork cells in an autonomic disorder. We determined the densities of VENs, fork cells, and pyramidal neurons and the ratio of VENs and fork cells to pyramidal neurons in ACC and FI in 4 FD patient and 6 matched control brains using a stereologic approach. We identified alterations in densities of VENs and pyramidal neurons and their distributions in the ACC and FI in FD brains. These data suggest that alterations in migration and numbers of VENs may be involved in FD pathophysiology thereby supporting the notion of a functional link between VENs, the ANS and the peripheral nervous system in general.

scholarly journals Unique membrane properties and enhanced signal processing in human neocortical neurons

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Guy Eyal ◽  
Matthijs B Verhoog ◽  
Guilherme Testa-Silva ◽  
Yair Deitcher ◽  
Johannes C Lodder ◽  
...  
Keyword(s):  
Signal Processing ◽  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Temporal Cortex ◽  
Building Blocks ◽  
Membrane Properties ◽  
Human Neocortex ◽  
Neocortical Neurons ◽  
Fitting In

The advanced cognitive capabilities of the human brain are often attributed to our recently evolved neocortex. However, it is not known whether the basic building blocks of the human neocortex, the pyramidal neurons, possess unique biophysical properties that might impact on cortical computations. Here we show that layer 2/3 pyramidal neurons from human temporal cortex (HL2/3 PCs) have a specific membrane capacitance (Cm) of ~0.5 µF/cm2, half of the commonly accepted 'universal' value (~1 µF/cm2) for biological membranes. This finding was predicted by fitting in vitro voltage transients to theoretical transients then validated by direct measurement of Cm in nucleated patch experiments. Models of 3D reconstructed HL2/3 PCs demonstrated that such low Cm value significantly enhances both synaptic charge-transfer from dendrites to soma and spike propagation along the axon. This is the first demonstration that human cortical neurons have distinctive membrane properties, suggesting important implications for signal processing in human neocortex.

scholarly journals Somato‐dendritic morphology and axon origin site specify von Economo neurons as a subclass of modified pyramidal neurons in the human anterior cingulate cortex

2019 ◽  
Vol 235 (3) ◽  
pp. 651-669 ◽  
Author(s):  
Ivan Banovac ◽  
Dora Sedmak ◽  
Domagoj Džaja ◽  
Dubravko Jalšovec ◽  
Nataša Jovanov Milošević ◽  
...  
Keyword(s):  
Anterior Cingulate Cortex ◽  
Pyramidal Neurons ◽  
Cingulate Cortex ◽  
Dendritic Morphology ◽  
Anterior Cingulate ◽  
Von Economo Neurons

scholarly journals The behavioral variant of Alzheimer's disease does not show a selective loss of Von Economo and phylogenetically related neurons in the anterior cingulate cortex

2021 ◽  
Author(s):  
Ellen Singleton ◽  
Yolande A.L. Pijnenburg ◽  
Priya Gami-Patel ◽  
Baayla D.C. Boon ◽  
Femke Bouwman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Anterior Cingulate Cortex ◽  
Pyramidal Neurons ◽  
Neuronal Loss ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Von Economo Neurons ◽  
Neuronal Populations ◽  
Selective Loss

Background: The neurobiological origins of the early and predominant behavioral changes seen in the behavioral variant of Alzheimer's disease (bvAD) remain unclear. A selective loss of Von Economo Neurons (VENs) and phylogenetically related neurons have been observed in behavioral variant frontotemporal dementia (bvFTD) and several psychiatric diseases. Here, we assessed whether these specific neuronal populations show a selective loss in bvAD. Methods: VENs and GABA receptor subunit theta (GABRQ)-immunoreactive pyramidal neurons of the anterior cingulate cortex (ACC) were quantified in post-mortem tissue of patients with bvAD (n=9) and compared to typical AD (tAD, n=6), bvFTD due to frontotemporal lobar degeneration based on TDP-43 pathology (FTLD, n=18) and controls (n=13) using ANCOVAs adjusted for age and Bonferroni corrected. In addition, ratios of VENs and GABRQ-immunoreactive (GABRQ-ir) pyramidal neurons over all Layer 5 neurons were compared between groups to correct for overall Layer 5 neuronal loss. Results: The number of VENs or GABRQ-ir neurons did not differ significantly between bvAD (VENs: 26.0±15.3, GABRQ-ir pyramidal: 260.44±87.13) and tAD (VENs: 32.0±18.1, p=1.00, GABRQ-ir pyramidal: 349.83±109.64, p=0.38) and controls (VENs: 33.5±20.3, p=1.00, GABRQ-ir pyramidal: 339.38±95.88, p=0.37). Compared to bvFTD, patients with bvAD showed significantly more GABRQ-ir pyramidal neurons (bvFTD: 140.39±82.58, p=0.01) and no significant differences in number of VENs (bvFTD: 10.9±13.8, p=0.13). Results were similar when assessing the number of VENs and GABRQ-ir relative to all neurons of Layer 5. Discussion: VENs and phylogenetically related neurons did not show a selective loss in the ACC in patients with bvAD. Our results suggest that, unlike in bvFTD, the clinical presentation in bvAD may not be related to the loss of VENs and related neurons in the ACC.

scholarly journals Von Economo Neurons – Primate-Specific or Commonplace in the Mammalian Brain?

2021 ◽  
Vol 15 ◽  
Author(s):  
Ivan Banovac ◽  
Dora Sedmak ◽  
Miloš Judaš ◽  
Zdravko Petanjek
Keyword(s):  
Cell Body ◽  
Pyramidal Neurons ◽  
Dendritic Morphology ◽  
Anterior Cingulate ◽  
Primate Species ◽  
Mammalian Brain ◽  
Extensive Literature ◽  
Von Economo Neurons ◽  
Unique Cell ◽  
Axonal Morphology

The pioneering work by von Economo in 1925 on the cytoarchitectonics of the cerebral cortex revealed a specialized and unique cell type in the adult human fronto-insular (FI) and anterior cingulate cortex (ACC). In modern studies, these neurons are termed von Economo neurons (VENs). In his work, von Economo described them as stick, rod or corkscrew cells because of their extremely elongated and relatively thin cell body clearly distinguishable from common oval or spindle-shaped infragranular principal neurons. Before von Economo, in 1899 Cajal depicted the unique somato-dendritic morphology of such cells with extremely elongated soma in the FI. However, although VENs are increasingly investigated, Cajal’s observation is still mainly being neglected. On Golgi staining in humans, VENs have a thick and long basal trunk with horizontally oriented terminal branching (basilar skirt) from where the axon arises. They are clearly distinguishable from a spectrum of modified pyramidal neurons found in infragranular layers, including oval or spindle-shaped principal neurons. Spindle-shaped cells with highly elongated cell body were also observed in the ACC of great apes, but despite similarities in soma shape, their dendritic and axonal morphology has still not been described in sufficient detail. Studies identifying VENs in non-human species are predominantly done on Nissl or anti-NeuN staining. In most of these studies, the dendritic and axonal morphology of the analyzed cells was not demonstrated and many of the cells found on Nissl or anti-NeuN staining had a cell body shape characteristic for common oval or spindle-shaped cells. Here we present an extensive literature overview on VENs, which demonstrates that human VENs are specialized elongated principal cells with unique somato-dendritic morphology found abundantly in the FI and ACC of the human brain. More research is needed to properly evaluate the presence of such specialized cells in other primates and non-primate species.

scholarly journals h-channels contribute to divergent electrophysiological properties of supragranular pyramidal neurons in human versus mouse cerebral cortex

2018 ◽  
Author(s):  
Brian E Kalmbach ◽  
Anatoly Buchin ◽  
Jeremy A Miller ◽  
Trygve E Bakken ◽  
Rebecca D Hodge ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Temporal Cortex ◽  
Membrane Properties ◽  
Temporal Association ◽  
Biophysical Modeling ◽  
Electrophysiological Properties ◽  
Channel Expression ◽  
Subunit Expression ◽  
Gene Expression Studies ◽  
H Channels

SummaryGene expression studies suggest that differential ion channel expression contributes to differences in rodent versus human neuronal physiology. We tested whether h-channels more prominently contribute to the physiological properties of human compared to mouse supragranular pyramidal neurons. Single cell/nucleus RNA sequencing revealed ubiquitous HCN1-subunit expression in excitatory neurons in human, but not mouse supragranular layers. Using patch-clamp recordings, we found stronger h-channel-related membrane properties in supragranular pyramidal neurons in human temporal cortex, compared to mouse supragranular pyramidal neurons in temporal association area. The magnitude of these differences depended upon cortical depth and was largest in pyramidal neurons in deep L3. Additionally, pharmacologically blocking h-channels produced a larger change in membrane properties in human compared to mouse neurons. Finally, using biophysical modeling, we provided evidence that h-channels promote the transfer of theta frequencies from dendrite-to-soma in human L3 pyramidal neurons. Thus, h-channels contribute to between-species differences in a fundamental neuronal property.

scholarly journals Control of impulsivity by Gi-protein signalling in layer-5 pyramidal neurons of the anterior cingulate cortex

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Bastiaan van der Veen ◽  
Sampath K. T. Kapanaiah ◽  
Kasyoka Kilonzo ◽  
Peter Steele-Perkins ◽  
Martin M. Jendryka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Anterior Cingulate Cortex ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Pyramidal Neurons ◽  
Treatment Options ◽  
Pyramidal Cells ◽  
Cingulate Cortex ◽  
Cell Types ◽  
Anterior Cingulate

AbstractPathological impulsivity is a debilitating symptom of multiple psychiatric diseases with few effective treatment options. To identify druggable receptors with anti-impulsive action we developed a systematic target discovery approach combining behavioural chemogenetics and gene expression analysis. Spatially restricted inhibition of three subdivisions of the prefrontal cortex of mice revealed that the anterior cingulate cortex (ACC) regulates premature responding, a form of motor impulsivity. Probing three G-protein cascades with designer receptors, we found that the activation of Gi-signalling in layer-5 pyramidal cells (L5-PCs) of the ACC strongly, reproducibly, and selectively decreased challenge-induced impulsivity. Differential gene expression analysis across murine ACC cell-types and 402 GPCRs revealed that - among Gi-coupled receptor-encoding genes - Grm2 is the most selectively expressed in L5-PCs while alternative targets were scarce. Validating our approach, we confirmed that mGluR2 activation reduced premature responding. These results suggest Gi-coupled receptors in ACC L5-PCs as therapeutic targets for impulse control disorders.

scholarly journals Septohippocampal transmission from parvalbumin-positive neurons features rapid recovery from synaptic depression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Feng Yi ◽  
Tavita Garrett ◽  
Karl Deisseroth ◽  
Heikki Haario ◽  
Emily Stone ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Synaptic Depression ◽  
Medial Septum ◽  
Membrane Properties ◽  
Projection Neurons ◽  
Calcium Dependent ◽  
Light Pulses ◽  
Diagonal Band ◽  
Initial Release ◽  
Intrinsic Membrane Properties

AbstractParvalbumin-containing projection neurons of the medial-septum-diagonal band of Broca ($$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB ) are essential for hippocampal rhythms and learning operations yet are poorly understood at cellular and synaptic levels. We combined electrophysiological, optogenetic, and modeling approaches to investigate $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB neuronal properties. $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB neurons had intrinsic membrane properties distinct from acetylcholine- and somatostatin-containing MS-DBB subtypes. Viral expression of the fast-kinetic channelrhodopsin ChETA-YFP elicited action potentials to brief (1–2 ms) 470 nm light pulses. To investigate $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB transmission, light pulses at 5–50 Hz frequencies generated trains of inhibitory postsynaptic currents (IPSCs) in CA1 stratum oriens interneurons. Using a similar approach, optogenetic activation of local hippocampal PV ($$\hbox {PV}_{\text{HC}}$$ PV HC ) neurons generated trains of $$\hbox {PV}_{\text{HC}}$$ PV HC -mediated IPSCs in CA1 pyramidal neurons. Both synapse types exhibited short-term depression (STD) of IPSCs. However, relative to $$\hbox {PV}_{\text{HC}}$$ PV HC synapses, $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB synapses possessed lower initial release probability, transiently resisted STD at gamma (20–50 Hz) frequencies, and recovered more rapidly from synaptic depression. Experimentally-constrained mathematical synapse models explored mechanistic differences. Relative to the $$\hbox {PV}_{\text{HC}}$$ PV HC model, the $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB model exhibited higher sensitivity to calcium accumulation, permitting a faster rate of calcium-dependent recovery from STD. In conclusion, resistance of $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB synapses to STD during short gamma bursts enables robust long-range GABAergic transmission from MS-DBB to hippocampus.

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