scholarly journals Comparing the Electrophysiology and Morphology of Human and Mouse Layer 2/3 Pyramidal Neurons With Bayesian Networks

2021 ◽  
Vol 15 ◽  
Author(s):  
Bojan Mihaljević ◽  
Pedro Larrañaga ◽  
Concha Bielza

Pyramidal neurons are the most common neurons in the cerebral cortex. Understanding how they differ between species is a key challenge in neuroscience. We compared human temporal cortex and mouse visual cortex pyramidal neurons from the Allen Cell Types Database in terms of their electrophysiology and dendritic morphology. We found that, among other differences, human pyramidal neurons had a higher action potential threshold voltage, a lower input resistance, and larger dendritic arbors. We learned Gaussian Bayesian networks from the data in order to identify correlations and conditional independencies between the variables and compare them between the species. We found strong correlations between electrophysiological and morphological variables in both species. In human cells, electrophysiological variables were correlated even with morphological variables that are not directly related to dendritic arbor size or diameter, such as mean bifurcation angle and mean branch tortuosity. Cortical depth was correlated with both electrophysiological and morphological variables in both species, and its effect on electrophysiology could not be explained in terms of the morphological variables. For some variables, the effect of cortical depth was opposite in the two species. Overall, the correlations among the variables differed strikingly between human and mouse neurons. Besides identifying correlations and conditional independencies, the learned Bayesian networks might be useful for probabilistic reasoning regarding the morphology and electrophysiology of pyramidal neurons.

2020 ◽  
Author(s):  
Bojan Mihaljević ◽  
Pedro Larrañaga ◽  
Concha Bielza

ABSTRACTPyramidal neurons are the most common neurons in the cerebral cortex. Understanding how they differ between species is a key challenge in neuroscience. We compared human temporal cortex and mouse visual cortex pyramidal neurons from the Allen Cell Types Database in terms of their electrophysiology and basal dendrites’ morphology. We found that, among other differences, human pyramidal neurons had a higher threshold voltage, a lower input resistance, and a larger basal dendritic arbor. We learned Gaussian Bayesian networks from the data in order to identify correlations and conditional independencies between the variables and compare them between the species. We found strong correlations between electrophysiological and morphological variables in both species. One result is that, in human cells, dendritic arbor width had the strongest effect on input resistance after accounting for the remaining variables. Electrophysiological variables were correlated, in both species, even with morphological variables that are not directly related to dendritic arbor size or diameter, such as mean bifurcation angle and mean branch tortuosity. Contrary to previous results, cortical depth was correlated with both electrophysiological and morphological variables, and its effect on electrophysiological could not be explained in terms of the morphological variables. Overall, the correlations among the variables differed strikingly between human and mouse neurons. Besides identifying correlations and conditional independencies, the learned Bayesian networks might be useful for probabilistic reasoning regarding the morphology and electrophysiology of pyramidal neurons.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Bojan Mihaljević ◽  
Pedro Larrañaga ◽  
Ruth Benavides-Piccione ◽  
Javier DeFelipe ◽  
Concha Bielza

Abstract Pyramidal neurons are the most common cell type in the cerebral cortex. Understanding how they differ between species is a key challenge in neuroscience. A recent study provided a unique set of human and mouse pyramidal neurons of the CA1 region of the hippocampus, and used it to compare the morphology of apical and basal dendritic branches of the two species. The study found inter-species differences in the magnitude of the morphometrics and similarities regarding their variation with respect to morphological determinants such as branch type and branch order. We use the same data set to perform additional comparisons of basal dendrites. In order to isolate the heterogeneity due to intrinsic differences between species from the heterogeneity due to differences in morphological determinants, we fit multivariate models over the morphometrics and the determinants. In particular, we use conditional linear Gaussian Bayesian networks, which provide a concise graphical representation of the independencies and correlations among the variables. We also extend the previous study by considering additional morphometrics and by formally testing whether a morphometric increases or decreases with the distance from the soma. This study introduces a multivariate methodology for inter-species comparison of morphology.


1989 ◽  
Vol 479 (1) ◽  
pp. 105-114 ◽  
Author(s):  
Jonathan M. Fitch ◽  
Janice M. Juraska ◽  
Lawrence W. Washington

2019 ◽  
Author(s):  
Akshay Gupta ◽  
Archana Proddutur ◽  
Yun-Juan Chang ◽  
Vidhatri Raturi ◽  
Jenieve Guevarra ◽  
...  

AbstractSemilunar granule cells (SGCs) have been proposed as a morpho-functionally distinct class of hippocampal dentate projection neurons contributing to feedback inhibition and memory processing in juvenile rats. However, the structural and physiological features that can reliably classify granule cells (GCs) from SGCs through postnatal development remain unresolved. Focusing on postnatal days 11-13, 28-42, and >120, corresponding with human infancy, adolescence, and adulthood, we examined the somatodendritic morphology and inhibitory regulation in SGCs and GCs to determine the cell-type specific features. Unsupervised cluster analysis confirmed that morphological features reliably distinguish SGCs from GCs irrespective of animal age. SGCs maintain higher spontaneous inhibitory postsynaptic current (sIPSC) frequency than GCs from infancy through adulthood. Although sIPSC frequency in SGCs was particularly enhanced during adolescence, sIPSC amplitude and cumulative charge transfer declined from infancy to adulthood and were not different between GCs and SGCs. Extrasynaptic GABA current amplitude peaked in adolescence in both cell types and was significantly greater in SGCs than in GCs only during adolescence. Although GC input resistance was higher than in SGCs during infancy and adolescence, input resistance decreased with developmental age in GCs while it progressively increased in SGCs. Consequently, GCs input resistance was significantly lower than SGCs in adults. The data delineate the structural features that can reliably distinguish GCs from SGCs through development. The results reveal developmental differences in passive membrane properties and steady state inhibition between GCs and SGCs which could confound their use in classifying the cell types.


2017 ◽  
Vol 27 (11) ◽  
pp. 5398-5414 ◽  
Author(s):  
Yair Deitcher ◽  
Guy Eyal ◽  
Lida Kanari ◽  
Matthijs B Verhoog ◽  
Guy Antoine Atenekeng Kahou ◽  
...  

Abstract There have been few quantitative characterizations of the morphological, biophysical, and cable properties of neurons in the human neocortex. We employed feature-based statistical methods on a rare data set of 60 3D reconstructed pyramidal neurons from L2 and L3 in the human temporal cortex (HL2/L3 PCs) removed after brain surgery. Of these cells, 25 neurons were also characterized physiologically. Thirty-two morphological features were analyzed (e.g., dendritic surface area, 36 333 ± 18 157 μm2; number of basal trees, 5.55 ± 1.47; dendritic diameter, 0.76 ± 0.28 μm). Eighteen features showed a significant gradual increase with depth from the pia (e.g., dendritic length and soma radius). The other features showed weak or no correlation with depth (e.g., dendritic diameter). The basal dendritic terminals in HL2/L3 PCs are particularly elongated, enabling multiple nonlinear processing units in these dendrites. Unlike the morphological features, the active biophysical features (e.g., spike shapes and rates) and passive/cable features (e.g., somatic input resistance, 47.68 ± 15.26 MΩ, membrane time constant, 12.03 ± 1.79 ms, average dendritic cable length, 0.99 ± 0.24) were depth-independent. A novel descriptor for apical dendritic topology yielded 2 distinct classes, termed hereby as “slim-tufted” and “profuse-tufted” HL2/L3 PCs; the latter class tends to fire at higher rates. Thus, our morpho-electrotonic analysis shows 2 distinct classes of HL2/L3 PCs.


2020 ◽  
Author(s):  
Bojan Mihaljević ◽  
Pedro Larrañaga ◽  
Ruth Benavides-Piccione ◽  
Javier DeFelipe ◽  
Concha Bielza

ABSTRACTPyramidal neurons are the most common cell type in the cerebral cortex. Understanding how they differ between species is a key challenge in neuroscience. A recent study provided a unique set of human and mouse pyramidal neurons of the CA1 region of the hippocampus, and used it to compare the morphology of apical and basal dendritic branches of the two species. The study found inter-species differences in the magnitude of the morphometrics and similarities regarding their variation with respect to morphological determinants such as branch type and branch order. We use the same data set to perform additional comparisons of basal dendrites. In order to isolate the heterogeneity due to intrinsic differences between species from the heterogeneity due to differences in morphological determinants, we fit multivariate models over the morphometrics and the determinants. In particular, we use conditional linear Gaussian Bayesian networks, which provide a concise graphical representation of the independencies and correlations among the variables. We also extend the previous study by considering additional morphometrics and by formally testing test whether a morphometric increases or decreases with the distance from the soma. This study introduces a multivariate methodology for inter-species comparison of morphology.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Bastiaan van der Veen ◽  
Sampath K. T. Kapanaiah ◽  
Kasyoka Kilonzo ◽  
Peter Steele-Perkins ◽  
Martin M. Jendryka ◽  
...  

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.


1987 ◽  
Vol 58 (5) ◽  
pp. 997-1015 ◽  
Author(s):  
M. Schmidt ◽  
M. F. Humphrey ◽  
H. Wassle

1. Retinal ganglion cells were recorded extracellularly in the intact eye of anesthetized adult cats. The effects of acetylcholine (ACh), the muscarinic antagonist scopolamine (Sco), the nicotinic antagonist dihydro-beta-erythroidine (DBE), and the acetylcholinesterase inhibitor physostigmine (Phy) on maintained and light-evoked ganglion cell discharge was examined using iontophoresis techniques. 2. A monoclonal antibody directed against the ACh synthesizing enzyme choline acetyltransferase (ChAT) was used to label cholinergic cells in retinal wholemounts. The topographical distribution of these cells was studied. 3. Intracellular filling with the fluorescent dye lucifer yellow (LY) was performed to identify the dendritic morphology of putative cholinergic neurons. 4. ACh increased and Sco decreased neuronal activity of all brisk ganglion cell types under all stimulus conditions tested in this study. The action of ACh was abolished during simultaneous application of Sco. 5. DBE raised the firing rate of ON-center brisk cells and decreased activity of OFF-center brisk cells. Again there was no difference under different stimulus conditions. During DBE application the ACh action on OFF-center cells was completely blocked. The ACh action on ON-center cells was diminished. 6. Phy prolonged and enhanced ACh action on all ganglion cell types. During simultaneous stimulation of the receptive-field center and the surround, Phy caused an activity shift in favor of the center response. 7. Immunocytochemical staining revealed two populations of amacrine cells, one in the inner nuclear layer, and the other in the ganglion cell layer. Their total density increased from 250 cells/mm2 in the periphery to 2,700 cells/mm2 in the central area. Analysis of the distribution pattern indicated a functional independence of the two subpopulations. 8. The dendritic morphology of putative cholinergic amacrine cells in the cat retina resembled that of rabbit and rat "starburst" amacrines, which are known to be cholinergic. 9. The possible function of cholinergic amacrine cells in the cat retina is discussed in view of the present findings and compared with results from other mammalian species.


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