Perisomatic Inhibition and Its Relation to Epilepsy and to Synchrony Generation in the Human Neocortex

Inhibitory neurons innervating the perisomatic region of cortical excitatory principal cells are known to control the emergence of several physiological and pathological synchronous events, including epileptic interictal spikes. In humans, little is known about their role in synchrony generation, although their changes in epilepsy have been thoroughly investigated. This paper demonstraits how parvalbumin (PV)- and type 1 cannabinoid receptor (CB1R)-positive perisomatic interneurons innervate pyramidal cell bodies, and their role in synchronous population events spontaneously emerging in the human epileptic and non-epileptic neocortex, in vitro. Quantitative electron microscopy showed that the overall, PV+ and CB1R+ somatic inhibitory inputs remained unchanged in focal cortical epilepsy. On the contrary, the size of PV-stained synapses increased, and their number decreased in epileptic samples, in synchrony generating regions. Pharmacology demonstrated—in conjunction with the electron microscopy—that although both perisomatic cell types participate, PV+ cells have stronger influence on the generation of population activity in epileptic samples. The somatic inhibitory input of neocortical pyramidal cells remained almost intact in epilepsy, but the larger and consequently more efficient somatic synapses might account for a higher synchrony in this neuron population. This, together with epileptic hyperexcitability, might make a cortical region predisposed to generate or participate in hypersynchronous events.

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Structure and function of axo-axonic inhibition

eLife ◽

10.7554/elife.73783 ◽

2021 ◽

Vol 10 ◽

Author(s):

Casey M Schneider-Mizell ◽

Agnes L Bodor ◽

Forrest Collman ◽

Derrick Brittain ◽

Adam Bleckert ◽

...

Keyword(s):

Electron Microscopy ◽

Large Scale ◽

Cell Activity ◽

Cell Types ◽

Structural Features ◽

Inhibitory Neurons ◽

Target Cells ◽

Population Activity ◽

Chandelier Cells

Inhibitory neurons in mammalian cortex exhibit diverse physiological, morphological, molecular and connectivity signatures. While considerable work has measured the average connectivity of several interneuron classes, there remains a fundamental lack of understanding of the connectivity distribution of distinct inhibitory cell types with synaptic resolution, how it relates to properties of target cells and how it affects function. Here, we used large-scale electron microscopy and functional imaging to address these questions for chandelier cells in layer 2/3 of the mouse visual cortex. With dense reconstructions from electron microscopy, we mapped the complete chandelier input onto 153 pyramidal neurons. We found that synapse number is highly variable across the population and is correlated with several structural features of the target neuron. This variability in the number of axo-axonic ChC synapses is higher than the variability seen in perisomatic inhibition. Biophysical simulations show that the observed pattern of axo-axonic inhibition is particularly effective in controlling excitatory output when excitation and inhibition are co-active. Finally, we measured chandelier cell activity in awake animals using a cell-type specific calcium imaging approach and saw highly correlated activity across chandelier cells. In the same experiments, in vivo chandelier population activity correlated with pupil dilation, a proxy for arousal. Together these results suggest that chandelier cells provide a circuit-wide signal whose strength is adjusted relative to the properties of target neurons.

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Synthesis and Evaluation of AlgNa-g-poly(QCL-co-HEMA) Hydrogels as Platform for Chondrocyte Proliferation and Controlled Release of Betamethasone

International Journal of Molecular Sciences ◽

10.3390/ijms22115730 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5730

Author(s):

Jomarien García-Couce ◽

Marioly Vernhes ◽

Nancy Bada ◽

Lissette Agüero ◽

Oscar Valdés ◽

...

Keyword(s):

Electron Microscopy ◽

Scanning Electron Microscopy ◽

Controlled Release ◽

Biomedical Applications ◽

Release Kinetics ◽

Cell Types ◽

Tissue Engineering Scaffolds ◽

Almost All ◽

Scanning Electron

Hydrogels obtained from combining different polymers are an interesting strategy for developing controlled release system platforms and tissue engineering scaffolds. In this study, the applicability of sodium alginate-g-(QCL-co-HEMA) hydrogels for these biomedical applications was evaluated. Hydrogels were synthesized by free-radical polymerization using a different concentration of the components. The hydrogels were characterized by Fourier transform-infrared spectroscopy, scanning electron microscopy, and a swelling degree. Betamethasone release as well as the in vitro cytocompatibility with chondrocytes and fibroblast cells were also evaluated. Scanning electron microscopy confirmed the porous surface morphology of the hydrogels in all cases. The swelling percent was determined at a different pH and was observed to be pH-sensitive. The controlled release behavior of betamethasone from the matrices was investigated in PBS media (pH = 7.4) and the drug was released in a controlled manner for up to 8 h. Human chondrocytes and fibroblasts were cultured on the hydrogels. The MTS assay showed that almost all hydrogels are cytocompatibles and an increase of proliferation in both cell types after one week of incubation was observed by the Live/Dead® assay. These results demonstrate that these hydrogels are attractive materials for pharmaceutical and biomedical applications due to their characteristics, their release kinetics, and biocompatibility.

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Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders

Molecules ◽

10.3390/molecules26113389 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3389

Author(s):

Ishtiaq Ahmed ◽

Saif Ur Rehman ◽

Shiva Shahmohamadnejad ◽

Muhammad Anjum Zia ◽

Muhammad Ahmad ◽

...

Keyword(s):

Cannabinoid Receptors ◽

Cannabinoid Receptor ◽

Therapeutic Potential ◽

Endocannabinoid System ◽

Cell Types ◽

Autoimmune Disorders ◽

Specific Receptors ◽

Different Cell Types

In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite. The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion. The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers. The therapeutic potential of cannabinoids for cancer—both in vivo and in vitro clinical trials—has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers. In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.

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Generation of Slow Network Oscillations in the Developing Rat Hippocampus After Blockade of Glutamate Uptake

Journal of Neurophysiology ◽

10.1152/jn.00378.2007 ◽

2007 ◽

Vol 98 (4) ◽

pp. 2324-2336 ◽

Cited By ~ 21

Author(s):

Adriano Augusto Cattani ◽

Valérie Delphine Bonfardin ◽

Alfonso Represa ◽

Yehezkel Ben-Ari ◽

Laurent Aniksztejn

Keyword(s):

Nmda Receptors ◽

Glutamate Uptake ◽

Pyramidal Cells ◽

Cell Types ◽

Proper Function ◽

Network Oscillations ◽

Bath Application ◽

Hippocampal Network

Cell-surface glutamate transporters are essential for the proper function of early cortical networks because their dysfunction induces seizures in the newborn rat in vivo. We have now analyzed the consequences of their inhibition by dl-TBOA on the activity of the developing CA1 rat hippocampal network in vitro. dl-TBOA generated a pattern of recurrent depolarization with an onset and decay of several seconds' duration in interneurons and pyramidal cells. These slow network oscillations (SNOs) were mostly mediated by γ-aminobutyric acid (GABA) in pyramidal cells and by GABA and N-methyl-d-aspartate (NMDA) receptors in interneurons. However, in both cell types SNOs were blocked by NMDA receptor antagonists, suggesting that their generation requires a glutamatergic drive. Moreover, in interneurons, SNOs were still generated after the blockade of NMDA-mediated synaptic currents with MK-801, suggesting that SNOs are expressed by the activation of extrasynaptic NMDA receptors. Long-lasting bath application of glutamate or NMDA failed to induce SNOs, indicating that they are generated by periodic but not sustained activation of NMDA receptors. In addition, SNOs were observed in interneurons recorded in slices with or without the strata pyramidale and oriens, suggesting that the glutamatergic drive may originate from the radiatum and pyramidale strata. We propose that in the absence of an efficient transport of glutamate, the transmitter diffuses in the extracellular space to activate extrasynaptic NMDA receptors preferentially present on interneurons that in turn activate other interneurons and pyramidal cells. This periodic neuronal coactivation may contribute to the generation of seizures when glutamate transport dysfunction is present.

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Cell-type specific innervation of cortical pyramidal cells at their apical dendrites

eLife ◽

10.7554/elife.46876 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 7

Author(s):

Ali Karimi ◽

Jan Odenthal ◽

Florian Drawitsch ◽

Kevin M Boergens ◽

Moritz Helmstaedter

Keyword(s):

Electron Microscopy ◽

Pyramidal Cells ◽

Inhibitory Input ◽

Cell Type ◽

Cell Type Specific ◽

Cortical Regions ◽

Apical Dendrites ◽

Computational Properties

We investigated the synaptic innervation of apical dendrites of cortical pyramidal cells in a region between layers (L) 1 and 2 using 3-D electron microscopy applied to four cortical regions in mouse. We found the relative inhibitory input at the apical dendrite’s main bifurcation to be more than 2-fold larger for L2 than L3 and L5 thick-tufted pyramidal cells. Towards the distal tuft dendrites in upper L1, the relative inhibitory input was at least about 2-fold larger for L5 pyramidal cells than for all others. Only L3 pyramidal cells showed homogeneous inhibitory input fraction. The inhibitory-to-excitatory synaptic ratio is thus specific for the types of pyramidal cells. Inhibitory axons preferentially innervated either L2 or L3/5 apical dendrites, but not both. These findings describe connectomic principles for the control of pyramidal cells at their apical dendrites and support differential computational properties of L2, L3 and subtypes of L5 pyramidal cells in cortex.

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The influence of jasmonic acid on the amount and the distribution of cysteine proteinase PLCP-2 in healthy and PVYNTN infected potato plants (Solanum tuberosum L.)

Plant Protection Science ◽

10.17221/10327-pps ◽

2002 ◽

Vol 38 (SI 1 - 6th Conf EFPP 2002) ◽

pp. S95-S98

Author(s):

M. Pompe-Novak ◽

M. Tušek-Žnidarič ◽

B. Štrukelj ◽

M. Ravnikar

Keyword(s):

Electron Microscopy ◽

Solanum Tuberosum ◽

Jasmonic Acid ◽

Cell Walls ◽

Cysteine Proteinase ◽

Solanum Tuberosum L ◽

Cell Types ◽

Protein Bodies ◽

Potato Plants

The localization of cysteine proteinase PLCP-2 was investigated in potato plants (Solanum tuberosum L.) cultivar Désirée by electron microscopy. Healthy and PVY<sup>NTN</sup> infected potato plants were grown in vitro on media with or without a supplement of jasmonic acid. We had already shown that PLCP-2 is present in leaves, stems, tips of shoots and tips of roots of healthy and PVY<sup>NTN</sup> infected plants. It was detected in various cell types in protein bodies in vacuoles, in cytoplasm and in cell walls. There were significantly larger amounts of PLCP-2 in plants grown on medium with a supplement of jasmonic acid in both healthy and virus infected plants. More protein bodies in vacuoles were found in plants grown on medium with addition of jasmonic acid.

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Electrophysiological Diversity of Layer 5 Pyramidal Cells in the Prefrontal Cortex of the Rhesus Monkey: In Vitro Slice Studies

Journal of Neurophysiology ◽

10.1152/jn.00585.2007 ◽

2007 ◽

Vol 98 (5) ◽

pp. 2622-2632 ◽

Cited By ~ 34

Author(s):

Yu-Ming Chang ◽

Jennifer I. Luebke

Keyword(s):

Prefrontal Cortex ◽

Rhesus Monkey ◽

Spike Train ◽

Pyramidal Cells ◽

Cell Types ◽

Dendritic Morphology ◽

Firing Patterns ◽

Electrophysiological Properties ◽

Whole Cell Patch Clamp

Whole cell patch-clamp recordings were employed to characterize the electrophysiological properties of layer 5 pyramidal cells in slices of the prefrontal cortex (Area 46) of the rhesus monkey. Four electrophysiologically distinct cell types were discriminated based on distinctive repetitive action potential (AP) firing patterns and single AP characteristics: regular-spiking slowly adapting type-1 cells (RS1; 62%), regular-spiking slowly adapting type-2 cells (RS2; 18%), regular-spiking fast-adapting cells (FA; 15%), and intrinsically bursting cells (IB; 5%). These cells did not differ with regard to their location in layer 5 nor in their dendritic morphology. In RS1 cells, AP threshold and amplitude did not change significantly during a 2-s spike train, whereas in RS2 and FA cells, AP threshold increased significantly and AP amplitude decreased significantly during the train. In FA cells, complete adaptation of AP firing was observed within 600 ms. IB cells displayed an all-or-none burst of three to six APs, followed by RS1-type firing behavior. RS1 cells could be further subdivided into three subtypes. Low-threshold spiking (LTS) RS1 cells exhibited an initial doublet riding on a depolarizing potential at the onset of a spike train and a prominent depolarizing afterpotential (DAP); intermediate RS1 cells (IM) exhibited a DAP, but no initial doublet, and non-LTS RS1 cells exhibited neither a DAP nor an initial doublet. RS2 and FA cells did not exhibit a DAP or initial doublets. The distinctive firing patterns of these diverse layer 5 pyramidal cells may reflect different roles played by these cells in the mediation of subcortical neuronal activity by the dorsolateral PFC.

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Surface topography of normal and neoplastic human anterior pituitary cells maintained in vitro

Journal of Neurosurgery ◽

10.3171/jns.1978.49.2.0169 ◽

1978 ◽

Vol 49 (2) ◽

pp. 169-178 ◽

Cited By ~ 5

Author(s):

Robert D. Harris ◽

Edward L. Seljeskog ◽

Kenneth J. Murray ◽

Shelley N. Chou ◽

William P. Cunningham ◽

...

Keyword(s):

Electron Microscopy ◽

Surface Topography ◽

Metastatic Cancer ◽

Pituitary Tumors ◽

Cell Types ◽

Pituitary Cells ◽

Content Type ◽

Transmission Electron ◽

Human Anterior Pituitary

✓ Pituitary tissues were obtained from 25 patients who underwent surgery for excision of pituitary macroadenomas, selective excision of microadenomas, or removal of a normal gland for palliation of metastatic cancer. Cells thus obtained were maintained in vitro for varying intervals, fixed, and examined by light (phase contrast), microscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Previous SEM reports indicate that surface topography of in vitro neoplastic cells displays features that may correlate with neoplastic behavior. Cultured normal and pituitary tumor cells did not display these surface differences, with one exception, a prolactin-secreting microadenoma. Characteristic patterns for the cell populations were identified. Certain cell types appeared in all the cultures: 1) large and small granule-containing cells; 2) flat and irregular agranular cells; 3) spindle-shaped cells; and 4) spherical, irregularly surfaced cells. In one case of an endocrine-inactive juvenile pituitary chromophobe adenoma, unique cells were observed. Surface topography did not appear to be of predictive value in determining the neoplastic character of pituitary tumors.

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Cell-type specific innervation of cortical pyramidal cells at their apical tufts

10.1101/571695 ◽

2019 ◽

Author(s):

Ali Karimi ◽

Jan Odenthal ◽

Florian Drawitsch ◽

Kevin M. Boergens ◽

Moritz Helmstaedter

Keyword(s):

Electron Microscopy ◽

Pyramidal Cells ◽

Inhibitory Input ◽

Cell Type ◽

Layer 2 ◽

Cell Type Specific ◽

Cortical Regions ◽

3D Em ◽

Apical Dendrites ◽

Computational Properties

ABSTRACTWe investigated the synaptic innervation of apical tufts of cortical pyramidal cells in a region between layers 1 and 2 using 3-D electron microscopy (3D-EM) applied to four cortical regions in mouse. Across all cortices, we found the relative inhibitory input at the apical dendrite’s main bifurcation to be more than 3-fold stronger for layer 2 pyramidal cells than for all other pyramidal cells. Towards the distal tuft dendrites in upper layer 1, however, the relative inhibitory input was about 2-fold stronger for L5 pyramidal cells than for all others. Only L3 pyramidal cells showed homogeneous inhibitory input density. The inhibitory to excitatory synaptic balance is thus specific for the types of pyramidal cells. Inhibitory axons preferentially innervated either layer 2 or L3/5 apical dendrites, but not both. These findings describe connectomic principles for the control of pyramidal cells at their apical dendrites in the upper layers of the cerebral cortex and point to differential computational properties of layer 2, layer 3 and layer 5 pyramidal cells in cortex.

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The Roles of Somatostatin-Expressing (GIN) and Fast-Spiking Inhibitory Interneurons in up-down States of Mouse Neocortex

Journal of Neurophysiology ◽

10.1152/jn.00206.2010 ◽

2010 ◽

Vol 104 (2) ◽

pp. 596-606 ◽

Cited By ~ 64

Author(s):

Erika E. Fanselow ◽

Barry W. Connors

Keyword(s):

Cell Types ◽

Inhibitory Neurons ◽

Up States ◽

Fast Spiking ◽

Cell Firing ◽

Up And Down States ◽

Cortical Circuit ◽

Network States ◽

Firing Characteristics

The neocortex contains multiple types of inhibitory neurons whose properties suggest they may play different roles within the cortical circuit. By recording from three cell types during two distinct network states (up and down states) in vitro, we were able to quantify differences in firing characteristics between these cells during different network regimes. We recorded from regular-spiking (RS) excitatory cells and two types of inhibitory neurons, the fast-spiking (FS) neurons and GFP- (and somatostatin-) expressing inhibitory neurons (GIN), in layer 2/3 of slices from mouse somatosensory neocortex. Comparisons of firing characteristics between these cells during up- and down-states showed several patterns. First, of these cell types, only GIN cells fired persistently during down-states, whereas all three cell types fired readily during up-states. Second, the onset of firing and distribution of action potentials throughout up-states differed by cell type, showing that FS cell up-state firing occurred preferentially near the beginning of the up-state, whereas the firing of RS cells was slower to develop at the start of the up-state, and GIN cell firing was sustained throughout the duration of the up-state. Finally, membrane potential and spike correlations between heterogeneous cell types were more pronounced during up-states and, in the case of RS synapses onto GIN cells, varied throughout the up-state. These results suggest that there is a division of labor between FS and GIN cells as the up-state progresses and suggest that GIN cells could be important in the termination of up-states.

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