Epileptiform activity in microcultures containing one excitatory hippocampal neuron

1991 ◽  
Vol 65 (4) ◽  
pp. 761-770 ◽  
Author(s):  
M. M. Segal
Keyword(s):  
Action Potentials ◽  
Epileptiform Activity ◽  
Inhibitory Neuron ◽  
Excitatory Neuron ◽  
Inhibitory Neurons ◽  
Gamma Aminobutyric Acid ◽  
Intracellular Recordings ◽  
Voltage Fluctuations ◽  
Excitatory Neurons ◽  
Small Voltage

1. Paroxysmal depolarizing shifts (PDSs) occur during interictal epileptiform activity. Sustained depolarizations are characteristic of ictal activity, and events resembling PDSs also occur during the sustained depolarizations. To study these elements of epileptiform activity in a simpler context, I used the in vitro chronic-excitatory-block model of epilepsy of Furshpan and Potter and the microculture technique of Segal and Furshpan. 2. Intracellular recordings were made from 93 single-neuron microcultures. Forty of these solitary neurons were excitatory, their action potentials were replaced by PDS-like events or sustained depolarizations as kynurenate was removed from the perfusion solution. PDS-like events were similar to PDSs in intact cortex, mass cultures, and microcultures with more than one neuron. Small voltage fluctuations were also seen in solitary excitatory neurons in the absence of recorded action potentials. Sustained depolarizations developed in 5 of the 40 excitatory neurons. Forty-eight of the 93 solitary neurons were inhibitory, with bicuculline-sensitive hyperpolarizations after the action potential (ascribable to gamma-aminobutyric acid-A autapses). None of the solitary inhibitory neurons displayed sustained depolarizations. Five of the 93 neurons were insensitive to both kynurenate and bicuculline and were not placed in either the excitatory or the inhibitory category. 3. Both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors contributed to the PDS-like events and sustained depolarizations. Only a non-NMDA glutamate receptor component was evident for the small voltage fluctuations. 4. Intracellular recordings were also made from two-neuron microcultures, each containing one excitatory neuron and one inhibitory neuron. Sustained depolarizations developed in five microcultures, in each case only in the excitatory neuron.

scholarly journals Cortical circuits implement optimal context integration

2017 ◽  
Author(s):  
Ramakrishnan Iyer ◽  
Stefan Mihalas
Keyword(s):  
Receptive Field ◽  
Large Scale ◽  
Inhibitory Neuron ◽  
Visual Input ◽  
Inhibitory Neurons ◽  
Specific Cell ◽  
Natural Scene ◽  
Cortical Circuits ◽  
Classical Receptive Field ◽  
Excitatory Neurons

Neurons in the primary visual cortex (V1) predominantly respond to a patch of the visual input, their classical receptive field. These responses are modulated by the visual input in the surround [2]. This reflects the fact that features in natural scenes do not occur in isolation: lines, surfaces are generally continuous, and the surround provides context for the information in the classical receptive field. It is generally assumed that the information in the near surround is transmitted via lateral connections between neurons in the same area [2]. A series of large scale efforts have recently described the relation between lateral connectivity and visual evoked responses and found like-to-like connectivity between excitatory neurons [16, 18]. Additionally, specific cell type connectivity for inhibitory neuron types has been described [11, 31]. Current normative models of cortical function relying on sparsity [27], saliency [4] predict functional inhibition between similarly tuned neurons. What computations are consistent with the observed structure of the lateral connections between the excitatory and diverse types of inhibitory neurons?We combined natural scene statistics [24] and mouse V1 neuron responses [7] to compute the lateral connections and computations of individual neurons which optimally integrate information from the classical receptive field with that from the surround by directly implementing Bayes rule. This increases the accuracy of representation of a natural scene under noisy conditions. We show that this network has like-to-like connectivity between excitatory neurons, similar to the observed one [16, 18, 11], and has three types of inhibition: local normalization, surround inhibition and gating of inhibition from the surround - that can be attributed to three classes of inhibitory neurons. We hypothesize that this computation: optimal integration of contextual cues with a gate to ignore context when necessary is a general property of cortical circuits, and the rules constructed for mouse V1 generalize to other areas and species.

scholarly journals Cell-autonomous role of Presenilin in age-dependent survival of cortical interneurons

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Jongkyun Kang ◽  
Jie Shen
Keyword(s):  
Cerebral Cortex ◽  
Inhibitory Neuron ◽  
Gabaergic Neurons ◽  
Inhibitory Neurons ◽  
Double Knockout ◽  
Normal Number ◽  
Cortical Interneurons ◽  
Age Dependent ◽  
Excitatory Neurons

Abstract Background Mutations in the PSEN1 and PSEN2 genes are the major cause of familial Alzheimer’s disease. Previous studies demonstrated that Presenilin (PS), the catalytic subunit of γ-secretase, is required for survival of excitatory neurons in the cerebral cortex during aging. However, the role of PS in inhibitory interneurons had not been explored. Methods To determine PS function in GABAergic neurons, we generated inhibitory neuron-specific PS conditional double knockout (IN-PS cDKO) mice, in which PS is selectively inactivated by Cre recombinase expressed under the control of the endogenous GAD2 promoter. We then performed behavioral, biochemical, and histological analyses to evaluate the consequences of selective PS inactivation in inhibitory neurons. Results IN-PS cDKO mice exhibit earlier mortality and lower body weight despite normal food intake and basal activity. Western analysis of protein lysates from various brain sub-regions of IN-PS cDKO mice showed significant reduction of PS1 levels and dramatic accumulation of γ-secretase substrates. Interestingly, IN-PS cDKO mice develop age-dependent loss of GABAergic neurons, as shown by normal number of GAD67-immunoreactive interneurons in the cerebral cortex at 2–3 months of age but reduced number of cortical interneurons at 9 months. Moreover, age-dependent reduction of Parvalbumin- and Somatostatin-immunoreactive interneurons is more pronounced in the neocortex and hippocampus of IN-PS cDKO mice. Consistent with these findings, the number of apoptotic cells is elevated in the cerebral cortex of IN-PS cDKO mice, and the enhanced apoptosis is due to dramatic increases of apoptotic interneurons, whereas the number of apoptotic excitatory neurons is unaffected. Furthermore, progressive loss of interneurons in the cerebral cortex of IN-PS cDKO mice is accompanied with astrogliosis and microgliosis. Conclusion Our results together support a cell-autonomous role of PS in the survival of cortical interneurons during aging. Together with earlier studies, these findings demonstrate a universal, essential requirement of PS in the survival of both excitatory and inhibitory neurons during aging.

Bridging the Functional and Wiring Properties of V1 Neurons Through Sparse Coding

2021 ◽  
pp. 1-34
Author(s):  
Xiaolin Hu ◽  
Zhigang Zeng
Keyword(s):  
Sparse Coding ◽  
Hebbian Learning ◽  
Inhibitory Neuron ◽  
Learning Rule ◽  
Orientation Selectivity ◽  
Inhibitory Neurons ◽  
Natural Scenes ◽  
Firing Rates ◽  
V1 Neurons ◽  
Excitatory Neurons

Abstract The functional properties of neurons in the primary visual cortex (V1) are thought to be closely related to the structural properties of this network, but the specific relationships remain unclear. Previous theoretical studies have suggested that sparse coding, an energy-efficient coding method, might underlie the orientation selectivity of V1 neurons. We thus aimed to delineate how the neurons are wired to produce this feature. We constructed a model and endowed it with a simple Hebbian learning rule to encode images of natural scenes. The excitatory neurons fired sparsely in response to images and developed strong orientation selectivity. After learning, the connectivity between excitatory neuron pairs, inhibitory neuron pairs, and excitatory-inhibitory neuron pairs depended on firing pattern and receptive field similarity between the neurons. The receptive fields (RFs) of excitatory neurons and inhibitory neurons were well predicted by the RFs of presynaptic excitatory neurons and inhibitory neurons, respectively. The excitatory neurons formed a small-world network, in which certain local connection patterns were significantly overrepresented. Bidirectionally manipulating the firing rates of inhibitory neurons caused linear transformations of the firing rates of excitatory neurons, and vice versa. These wiring properties and modulatory effects were congruent with a wide variety of data measured in V1, suggesting that the sparse coding principle might underlie both the functional and wiring properties of V1 neurons.

scholarly journals Implications of Extended Inhibitory Neuron Development

2021 ◽  
Vol 22 (10) ◽  
pp. 5113
Author(s):  
Jae-Yeon Kim ◽  
Mercedes F. Paredes
Keyword(s):  
Neural Circuit ◽  
Inhibitory Neuron ◽  
Postnatal Period ◽  
Specific Pattern ◽  
Inhibitory Neurons ◽  
Gabaergic Interneuron ◽  
Gabaergic Interneurons ◽  
Neuron Development ◽  
Cortical Regions ◽  
Circuit Formation

A prolonged developmental timeline for GABA (γ-aminobutyric acid)-expressing inhibitory neurons (GABAergic interneurons) is an amplified trait in larger, gyrencephalic animals. In several species, the generation, migration, and maturation of interneurons take place over several months, in some cases persisting after birth. The late integration of GABAergic interneurons occurs in a region-specific pattern, especially during the early postnatal period. These changes can contribute to the formation of functional connectivity and plasticity, especially in the cortical regions responsible for higher cognitive tasks. In this review, we discuss GABAergic interneuron development in the late gestational and postnatal forebrain. We propose the protracted development of interneurons at each stage (neurogenesis, neuronal migration, and network integration), as a mechanism for increased complexity and cognitive flexibility in larger, gyrencephalic brains. This developmental feature of interneurons also provides an avenue for environmental influences to shape neural circuit formation.

scholarly journals Amyloid-β Oligomers Induce Only Mild Changes to Inhibitory Bouton Dynamics

2021 ◽  
Vol 5 (1) ◽  
pp. 153-160 ◽  
Author(s):  
Marvin Ruiter ◽  
Christine Lützkendorf ◽  
Jian Liang ◽  
Corette J. Wierenga
Keyword(s):  
Hippocampal Slices ◽  
Inhibitory Neuron ◽  
Amyloid Β ◽  
Inhibitory Neurons ◽  
Inhibitory Synapses ◽  
Amyloid Β Protein ◽  
Protein Precursor ◽  
Β Protein ◽  
Plaque Load ◽  
Early Alzheimer’S Disease

The amyloid-β protein precursor is highly expressed in a subset of inhibitory neuron in the hippocampus, and inhibitory neurons have been suggested to play an important role in early Alzheimer’s disease plaque load. Here we investigated bouton dynamics in axons of hippocampal interneurons in two independent amyloidosis models. Short-term (24 h) amyloid-β (Aβ)-oligomer application to organotypic hippocampal slices slightly increased inhibitory bouton dynamics, but bouton density and dynamics were unchanged in hippocampus slices of young-adult AppNL - F - G-mice, in which Aβ levels are chronically elevated. These results indicate that loss or defective adaptation of inhibitory synapses are not a major contribution to Aβ-induced hyperexcitability.

scholarly journals Neuron-specific spinal cord translatomes reveal a neuropeptide code for mouse dorsal horn excitatory neurons

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rebecca Rani Das Gupta ◽  
Louis Scheurer ◽  
Pawel Pelczar ◽  
Hendrik Wildner ◽  
Hanns Ulrich Zeilhofer
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Functional Organization ◽  
Affinity Purification ◽  
Expression Patterns ◽  
Inhibitory Neurons ◽  
Dorsal Horn Neurons ◽  
Expression Of Genes ◽  
Excitatory Neurons ◽  
Genes Encoding

AbstractThe spinal dorsal horn harbors a sophisticated and heterogeneous network of excitatory and inhibitory neurons that process peripheral signals encoding different sensory modalities. Although it has long been recognized that this network is crucial both for the separation and the integration of sensory signals of different modalities, a systematic unbiased approach to the use of specific neuromodulatory systems is still missing. Here, we have used the translating ribosome affinity purification (TRAP) technique to map the translatomes of excitatory glutamatergic (vGluT2+) and inhibitory GABA and/or glycinergic (vGAT+ or Gad67+) neurons of the mouse spinal cord. Our analyses demonstrate that inhibitory and excitatory neurons are not only set apart, as expected, by the expression of genes related to the production, release or re-uptake of their principal neurotransmitters and by genes encoding for transcription factors, but also by a differential engagement of neuromodulator, especially neuropeptide, signaling pathways. Subsequent multiplex in situ hybridization revealed eleven neuropeptide genes that are strongly enriched in excitatory dorsal horn neurons and display largely non-overlapping expression patterns closely adhering to the laminar and presumably also functional organization of the spinal cord grey matter.

Electrical interactions between the giant axons of a polychaete worm (Sabella penicillus L.)

1980 ◽  
Vol 84 (1) ◽  
pp. 119-136
Author(s):  
D. Mellon ◽  
J. E. Treherne ◽  
N. J. Lane ◽  
J. B. Harrison ◽  
C. K. Langley
Keyword(s):  
Safety Factor ◽  
Nerve Cord ◽  
Action Potentials ◽  
Divalent Cations ◽  
Muscular Contraction ◽  
The Body ◽  
The Other ◽  
Intracellular Recordings ◽  
Giant Axons ◽  
Other Hand

Intracellular recordings demonstrated a transfer of impulses between the paired giant axons of Sabella, apparently along narrow axonal processes contained within the paired commissures which link the nerve cords in each segment of the body. This transfer appears not to be achieved by chemical transmission, as has been previously supposed. This is indicated by the spread of depolarizing and hyperpolarizing voltage changes between the giant axons, the lack of effects of changes in the concentrations of external divalent cations on impulse transmission and by the effects of hyperpolarization in reducing the amplitude of the depolarizing potential which precedes the action potentials in the follower axon. The ten-to-one attenuation of electronic potentials between the giant axons argues against the possibility of an exclusively passive spread of potential along the axonal processes which link the axons. Observation of impulse traffic within the nerve cord commissures indicates, on the other hand, that transmission is achieved by conduction of action potentials along the axonal processes which link the giant axons. At least four pairs of intact commissures are necessary for inter-axonal transmission, the overall density of current injected at multiple sites on the follower axon being, it is presumed, sufficient to overcome the reduction in safety factor imposed by the geometry of the system in the region where axonal processes join the giant axons. The segmental transmission between the giant axons ensures effective synchronization of impulse traffic initiated in any region of the body and, thus, co-ordination of muscular contraction, during rapid withdrawal responses of the worm.

scholarly journals Mechanisms underlying contrast-dependent orientation selectivity in mouse V1

2018 ◽  
Vol 115 (45) ◽  
pp. 11619-11624 ◽  
Author(s):  
Wei P. Dai ◽  
Douglas Zhou ◽  
David W. McLaughlin ◽  
David Cai
Keyword(s):  
Large Scale ◽  
Feedback Inhibition ◽  
Orientation Selectivity ◽  
Inhibitory Neurons ◽  
Orientation Tuning ◽  
Response Properties ◽  
Firing Rates ◽  
Excitatory Neurons ◽  
Cortical Excitation ◽  
Contrast Invariance

Recent experiments have shown that mouse primary visual cortex (V1) is very different from that of cat or monkey, including response properties—one of which is that contrast invariance in the orientation selectivity (OS) of the neurons’ firing rates is replaced in mouse with contrast-dependent sharpening (broadening) of OS in excitatory (inhibitory) neurons. These differences indicate a different circuit design for mouse V1 than that of cat or monkey. Here we develop a large-scale computational model of an effective input layer of mouse V1. Constrained by experiment data, the model successfully reproduces experimentally observed response properties—for example, distributions of firing rates, orientation tuning widths, and response modulations of simple and complex neurons, including the contrast dependence of orientation tuning curves. Analysis of the model shows that strong feedback inhibition and strong orientation-preferential cortical excitation to the excitatory population are the predominant mechanisms underlying the contrast-sharpening of OS in excitatory neurons, while the contrast-broadening of OS in inhibitory neurons results from a strong but nonpreferential cortical excitation to these inhibitory neurons, with the resulting contrast-broadened inhibition producing a secondary enhancement on the contrast-sharpened OS of excitatory neurons. Finally, based on these mechanisms, we show that adjusting the detailed balances between the predominant mechanisms can lead to contrast invariance—providing insights for future studies on contrast dependence (invariance).

SIMULATING VERTICAL AND HORIZONTAL INHIBITION WITH SHORT-TERM DYNAMICS IN A MULTI-COLUMN MULTI-LAYER MODEL OF NEOCORTEX

2014 ◽  
Vol 24 (05) ◽  
pp. 1440002 ◽  
Author(s):  
BEATA STRACK ◽  
KIMBERLE M. JACOBS ◽  
KRZYSZTOF J. CIOS
Keyword(s):  
Epileptiform Activity ◽  
Inhibitory Neuron ◽  
Normal Function ◽  
Spiking Neurons ◽  
Layer Model ◽  
Neuronal Connectivity ◽  
Short Term ◽  
Short Term Plasticity ◽  
Low Threshold ◽  
Fast Spiking

The paper introduces a multi-layer multi-column model of the cortex that uses four different neuron types and short-term plasticity dynamics. It was designed with details of neuronal connectivity available in the literature and meets these conditions: (1) biologically accurate laminar and columnar flows of activity, (2) normal function of low-threshold spiking and fast spiking neurons, and (3) ability to generate different stages of epileptiform activity. With these characteristics the model allows for modeling lesioned or malformed cortex, i.e. examine properties of developmentally malformed cortex in which the balance between inhibitory neuron subtypes is disturbed.

Changes in gamma-aminobutyric acid and somatostatin in epileptic cortex associated with low-grade gliomas

1992 ◽  
Vol 77 (2) ◽  
pp. 209-216 ◽  
Author(s):  
Michael M. Haglund ◽  
Mitchel S. Berger ◽  
Dennis D. Kunkel ◽  
JoAnn E. Franck ◽  
Saadi Ghatan ◽  
...  
Keyword(s):  
Epileptiform Activity ◽  
Aminobutyric Acid ◽  
Low Grade ◽  
Tumor Infiltration ◽  
Gamma Aminobutyric Acid ◽  
Content Type ◽  
Low Grade Gliomas ◽  
Neuronal Populations ◽  
Significant Difference

✓ The role of specific neuronal populations in epileptic foci was studied by comparing epileptic and nonepileptic cortex removed from patients with low-grade gliomas. Epileptic and nearby (within 1 to 2 cm) nonepileptic temporal lobe neocortex was identified using electrocorticography. Cortical specimens taken from four patients identified as epileptic and nonepileptic were all void of tumor infiltration. Somatostatin- and γ-aminobutyric acid (GABAergic)-immunoreactive neurons were identified and counted. Although there was no significant difference in the overall cell count, the authors found a significant decrease in both somatostatin- and GABAergic-immunoreactive neurons (74% and 51 %, respectively) in the epileptic cortex compared to that in nonepileptic cortex from the same patient. It is suggested that these findings demonstrate changes in neuronal subpopulations that may account for the onset and propagation of epileptiform activity in patients with low-grade gliomas.

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