scholarly journals Cestode larvae excite host neuronal circuits via glutamatergic signaling

2019 ◽  
Author(s):  
Hayley Tomes ◽  
Anja de Lange ◽  
Ulrich Fabien Prodjinotho ◽  
Siddhartha Mahanty ◽  
Katherine Smith ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Imaging Techniques ◽  
Taenia Solium ◽  
Brain Slices ◽  
Receptor Activation ◽  
Excitatory Effect ◽  
Excitatory Neurotransmitter ◽  
Acquired Epilepsy ◽  
The Brain

AbstractNeurocysticercosis (NCC) is caused by the presence of Taenia solium larvae in the brain and is the leading cause of adult-acquired epilepsy worldwide. However, little is known about how seizures emerge in NCC. To address this knowledge gap we used whole-cell patch-clamp electrophysiology and calcium imaging in rodent hippocampal organotypic slice cultures to identify direct effects of cestode larval products on neuronal activity. We found both whole cyst homogenate and excretory/secretory (E/S) products of Taenia larvae have an acute excitatory effect on neurons, which trigger seizure-like events in vitro. Underlying this effect was Taenia-induced neuronal depolarization, which was mediated by glutamate receptor activation but not by nicotinic acetylcholine receptors, acid-sensing ion channels nor Substance P. Glutamate assays revealed the homogenate of both Taenia crassiceps and Taenia solium larvae contained high concentrations of glutamate and that larvae of both species consistently produce and release this excitatory neurotransmitter into their immediate environment. These findings contribute towards the understanding of seizure generation in NCC.Author summaryBrain infection by larvae of the tapeworm Taenia solium (neurocysticercosis or NCC) is the leading cause of acquired epilepsy in adulthood. Little is understood about the mechanisms by which larvae cause seizures. To address this, we used electrophysiological and imaging techniques in rodent brain slices to investigate how tapeworm larvae directly impact neuronal function. We discovered that both the homogenate and secretory products of tapeworm larvae excite neurons and can trigger seizure-like events in brain slices. This effect was caused by the activation of glutamate receptors and not by activating other types of receptors in the brain. Finally, we observed that tapeworm larvae both contain and release the neurotransmitter glutamate into their immediate environment. These findings are relevant for understanding how tapeworm larvae cause seizures in NCC.

Physiology, Pharmacology, and Topography of Cholinergic Neocortical Oscillations In Vitro

1997 ◽  
Vol 77 (5) ◽  
pp. 2427-2445 ◽  
Author(s):  
Heath S. Lukatch ◽  
M. Bruce Maciver
Keyword(s):  
Current Source ◽  
Brain Slices ◽  
Receptor Activation ◽  
Brain Regions ◽  
Oscillatory Activity ◽  
Cortical Layers ◽  
Eeg Activity ◽  
Layer 2

Lukatch, Heath S. and M. Bruce MacIver. Physiology, pharmacology, and topography of cholinergic neocortical oscillations in vitro. J. Neurophysiol. 77: 2427–2445, 1997. Rat neocortical brain slices generated rhythmic extracellular field [microelectroencephalogram (micro-EEG)] oscillations at theta frequencies (3–12 Hz) when exposed to pharmacological conditions that mimicked endogenous ascending cholinergic and GABAergic inputs. Use of the specific receptor agonist and antagonist carbachol and bicuculline revealed that simultaneous muscarinic receptor activation and γ-aminobutyric acid-A (GABAA)-mediated disinhibition werenecessary to elicit neocortical oscillations. Rhythmic activity was independent of GABAB receptor activation, but required intact glutamatergic transmission, evidenced by blockade or disruption of oscillations by 6-cyano-7-nitroquinoxaline-2,3-dione and (±)-2-amino-5-phosphonovaleric acid, respectively. Multisite mapping studies showed that oscillations were localized to areas 29d and 18b (Oc2MM) and parts of areas 18a and 17. Peak oscillation amplitudes occurred in layer 2/3, and phase reversals were observed in layers 1 and 5. Current source density analysis revealed large-amplitude current sinks and sources in layers 2/3 and 5, respectively. An initial shift in peak inward current density from layer 1 to layer 2/3 indicated that two processes underlie an initial depolarization followed by oscillatory activity. Laminar transections localized oscillation-generating circuitry to superficial cortical layers and sharp-spike-generating circuitry to deep cortical layers. Whole cell recordings identified three distinct cell types based on response properties during rhythmic micro-EEG activity: oscillation-on (theta-on) and -off (theta-off) neurons, and transiently depolarizing glial cells. Theta-on neurons displayed membrane potential oscillations that increased in amplitude with hyperpolarization (from −30 to −90 mV). This, taken together with a glutamate antagonist-induced depression of rhythmic micro-EEG activity, indicated that cholinergically driven neocortical oscillations require excitatory synaptic transmission. We conclude that under the appropriate pharmacological conditions, neocortical brain slices were capable of producing localized theta frequency oscillations. Experiments examining oscillation physiology, pharmacology, and topography demonstrated that neocortical brain slice oscillations share many similarities with the in vivo and in vitro theta EEG activity recorded in other brain regions.

TMOD-31. AN ORGANOTYPIC TISSUE PLATFORM TO BRIDGE IN VITRO AND IN VIVO ASSAYS FOR BRAIN CANCER TREATMENT

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi222-vi222
Author(s):  
Breanna Mann ◽  
Noah Bell ◽  
Denise Dunn ◽  
Scott Floyd ◽  
Shawn Hingtgen ◽  
...  
Keyword(s):  
Cell Lines ◽  
Brain Cancer ◽  
Brain Slice ◽  
Brain Slices ◽  
In Vitro Assays ◽  
Preclinical Model ◽  
Short Period ◽  
The Brain

Abstract Brain cancers remain one of the greatest medical challenges. The lack of experimentally tractable models that recapitulate brain structure/function represents a major impediment. Platforms that enable functional testing in high-fidelity models are urgently needed to accelerate the identification and translation of therapies to improve outcomes for patients suffering from brain cancer. In vitro assays are often too simple and artificial while in vivo studies can be time-intensive and complicated. Our live, organotypic brain slice platform can be used to seed and grow brain cancer cell lines, allowing us to bridge the existing gap in models. These tumors can rapidly establish within the brain slice microenvironment, and morphologic features of the tumor can be seen within a short period of time. The growth, migration, and treatment dynamics of tumors seen on the slices recapitulate what is observed in vivo yet is missed by in vitro models. Additionally, the brain slice platform allows for the dual seeding of different cell lines to simulate characteristics of heterogeneous tumors. Furthermore, live brain slices with embedded tumor can be generated from tumor-bearing mice. This method allows us to quantify tumor burden more effectively and allows for treatment and retreatment of the slices to understand treatment response and resistance that may occur in vivo. This brain slice platform lays the groundwork for a new clinically relevant preclinical model which provides physiologically relevant answers in a short amount of time leading to an acceleration of therapeutic translation.

scholarly journals The metabolism of polyphosphoinositides in hen brain and sciatic nerve

1969 ◽  
Vol 111 (2) ◽  
pp. 157-165 ◽  
Author(s):  
A. Sheltawy ◽  
R. M. C. Dawson
Keyword(s):  
Sciatic Nerve ◽  
Previous Investigation ◽  
Relative Rate ◽  
Specific Radioactivity ◽  
Brain Slices ◽  
Soluble Phosphorus ◽  
Ethanolamine Plasmalogen ◽  
32P Incorporation ◽  
The Brain

1. The distribution of individual phospholipids was determined in hen brain and compared with that in sciatic nerve obtained in a previous investigation. Sciatic nerve is more enriched in the myelinic phospholipids ethanolamine plasmalogen, phosphatidylserine and sphingomyelin, but it contains relatively less triphosphoinositide, and much less diphosphoinositide, than the brain. 2. The course of incorporation of intraperitoneally injected 32P into the acid-soluble phosphorus, phosphoinositides and total phospholipids of hen brain and sciatic nerve was followed. Although the maximum specific radioactivity in sciatic nerve of acid-soluble phosphorus is 4·5 times, and that of triphosphoinositide six times, that in the brain, the relative rate of triphosphoinositide phosphorus synthesis per gram of brain is three times that in sciatic nerve. 3. Administration of the demyelinating agent tri-o-cresyl phosphate to hens has no significant effect on the amounts or the rate of 32P incorporation into the total phospholipids of the sciatic nerve. However, the rate of incorporation of 32P into triphosphoinositide, although not its concentration, is raised from the first day after administration of the drug and remains thus 13 and 23 days later. 4. The incorporation of 32P into polyphosphoinositides of hen brain slices in vitro was studied. The recovery of triphosphoinositide from the slices is markedly increased in the presence of EDTA, although the rate of incorporation of 32P is unaffected. The incorporation of 32P is dependent on the presence of Mg2+ and Ca2+ in the medium, and is decreased when Na+ is replaced with K+ or cholinium ions.

Expression patterns of nicotinic subunits α2, α7, α8, and β1 affect the kinetics and pharmacology of ACh-induced currents in adult bee olfactory neuropiles

2011 ◽  
Vol 106 (4) ◽  
pp. 1604-1613 ◽  
Author(s):  
Julien Pierre Dupuis ◽  
Monique Gauthier ◽  
Valérie Raymond-Delpech
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Expression Patterns ◽  
Insect Brain ◽  
Olfactory Pathway ◽  
Excitatory Neurotransmitter ◽  
Kenyon Cells ◽  
Inward Currents ◽  
Induced Currents ◽  
The Brain

Acetylcholine (ACh) is the main excitatory neurotransmitter of the insect brain, where nicotinic acetylcholine receptors (nAChRs) mediate fast cholinergic synaptic transmission. In the honeybee Apis mellifera, nAChRs are expressed in diverse structures including the primary olfactory centers of the brain, the antennal lobes (ALs) and the mushroom bodies (MBs), where they participate in olfactory information processing. To understand the nature and properties of the nAChRs involved in these processes, we performed a pharmacological and molecular characterization of nAChRs on cultured Kenyon cells of the MBs, using whole cell patch-clamp recordings combined with single-cell RT-PCR. In all cells, applications of ACh as well as nicotinic agonists such as nicotine and imidacloprid induced inward currents with fast desensitization. These currents were fully blocked by saturating doses of the antagonists α-bungarotoxin (α-BGT), dihydroxy-β-erythroidine (DHE), and methyllycaconitine (MLA) (MLA ≥ α-BGT ≥ DHE). Molecular analysis of ACh-responding cells revealed that of the 11 nicotinic receptor subunits encoded within the honeybee genome, α2, α8, and β1 subunits were expressed in adult Kenyon cells. Comparison with the expression pattern of adult AL cells revealed the supplementary presence of subunit α7, which could be responsible for the kinetic and pharmacological differences observed when comparing ACh-induced currents from AL and Kenyon cells. Together, our data demonstrate the existence of functional nAChRs on adult MB Kenyon cells that differ from nAChRs on AL cells in both their molecular composition and pharmacological properties, suggesting that changing receptor subsets could mediate different processing functions depending on the brain structure within the olfactory pathway.

scholarly journals A Review of Neurotransmitters Sensing Methods for Neuro-Engineering Research

2019 ◽  
Vol 9 (21) ◽  
pp. 4719 ◽  
Author(s):  
Shimwe Dominique Niyonambaza ◽  
Praveen Kumar ◽  
Paul Xing ◽  
Jessy Mathault ◽  
Paul De Koninck ◽  
...  
Keyword(s):  
Imaging Techniques ◽  
Ongoing Research ◽  
Engineering Research ◽  
Detection Techniques ◽  
In Vivo Detection ◽  
Low Concentrations ◽  
The Subject ◽  
The Brain

Neurotransmitters as electrochemical signaling molecules are essential for proper brain function and their dysfunction is involved in several mental disorders. Therefore, the accurate detection and monitoring of these substances are crucial in brain studies. Neurotransmitters are present in the nervous system at very low concentrations, and they mixed with many other biochemical molecules and minerals, thus making their selective detection and measurement difficult. Although numerous techniques to do so have been proposed in the literature, neurotransmitter monitoring in the brain is still a challenge and the subject of ongoing research. This article reviews the current advances and trends in neurotransmitters detection techniques, including in vivo sampling and imaging techniques, electrochemical and nano-object sensing techniques for in vitro and in vivo detection, as well as spectrometric, analytical and derivatization-based methods mainly used for in vitro research. The document analyzes the strengths and weaknesses of each method, with the aim to offer selection guidelines for neuro-engineering research.

Effect of Withdrawal from Chronic Ethanol Ingestion on the cAMP Response of Cerebral Cortical Slices Using the Agonists Histamine, Serotonin, and Other Neurotransmitters

1975 ◽  
Vol 53 (2) ◽  
pp. 248-255 ◽  
Author(s):  
Samuel W. French ◽  
Douglas S. Palmer ◽  
Mary E. Narod
Keyword(s):  
Brain Slices ◽  
Ethanol Withdrawal ◽  
Aminobutyric Acid ◽  
Ethanol Ingestion ◽  
Evoked Responses ◽  
Alternative Hypotheses ◽  
Adrenergic Antagonists ◽  
The Brain ◽  
Cortical Slices

The effect of ethanol withdrawal on the cAMP response of cerebral cortical brain slices was studied. The cAMP response was evoked in vitro by various neurotransmitters including norepinephrine (NE), histamine, serotonin, dopamine, acetylcholine, and γ-aminobutyric acid (GABA). The cAMP response to NE and histamine was enhanced by ethanol withdrawal. Serotonin evoked a cAMP response in the brain slices from ethanol-withdrawal rats but not in pair-fed controls. The histamine and serotonin evoked responses were blocked by chlortripolon and methysergide, respectively. The responses to histamine and serotonin were also blocked by a- and β-adrenergic antagonists, possibly because of the nonspecific membrane stabilizing effect of these antagonists. GABA inhibited the NE stimulated cAMP response possibly through the hyperpolarizing action of GABA. The results support the hypothesis that ethanol withdrawal induces a nonspecific postjunctional supersensitivity. It is postulated that the supersensitivity involves a partial depolarization of the receptor membrane. Alternative hypotheses are reviewed.

Dopamine Modulates Excitability of Basolateral Amygdala Neurons In Vitro

2005 ◽  
Vol 93 (3) ◽  
pp. 1598-1610 ◽  
Author(s):  
Sven Kröner ◽  
J. Amiel Rosenkranz ◽  
Anthony A. Grace ◽  
German Barrionuevo
Keyword(s):  
Basolateral Amygdala ◽  
Neuronal Response ◽  
Brain Slices ◽  
Receptor Activation ◽  
D1 Receptor ◽  
In Vivo Studies ◽  
Projection Neurons ◽  
Direct Effects

The amygdala plays a role in affective behaviors, which are modulated by the dopamine (DA) innervation of the basolateral amygdala complex (BLA). Although in vivo studies indicate that activation of DA receptors alters BLA neuronal activity, it is unclear whether DA exerts direct effects on BLA neurons or whether it acts via indirect effects on BLA afferents. Using whole cell patch-clamp recordings in rat brain slices, we investigated the site and mechanisms through which DA regulates the excitability of BLA neurons. Dopamine enhanced the excitability of BLA projection neurons in response to somatic current injections via a postsynaptic effect. Dopamine D1 receptor activation increased excitability and evoked firing, whereas D2 receptor activation increased input resistance. Current- and voltage-clamp experiments in projection neurons showed that D1 receptor activation enhanced excitability by modulating a 4-aminopyridine- and α-dendrotoxin-sensitive, slowly inactivating K+ current. Furthermore, DA and D1 receptor activation increased evoked firing in fast-spiking BLA interneurons. Consistent with a postsynaptic modulation of interneuron excitability, DA also increased the frequency of spontaneous inhibitory postsynaptic currents recorded in projection neurons without changing release of GABA. These data demonstrate that DA exerts direct effects on BLA projection neurons and indirect actions via modulation of interneurons that may work in concert to enhance the neuronal response to large, suprathreshold inputs, while suppressing weaker inputs.

Biochemistry

1936 ◽  
Vol 82 (339) ◽  
pp. 431-433
Author(s):  
J. H. Quastel
Keyword(s):  
Nervous System ◽  
Brain Tissue ◽  
Brain Slice ◽  
Brain Slices ◽  
Ringer Solution ◽  
Living Animal ◽  
Dominant Form ◽  
Straight Line ◽  
The Brain

I want to speak of the work we have been doing in Cardiff on the metabolism of the nervous system. The work was carried out there because of the importance of the narcosis treatment. It seemed to us there a pity that a treatment such as that should be given up because of the considerable toxicity possible in relation to it. The research was undertaken to see if we could diminish the toxicity, at the same time seeking an idea as to how narcotics work. I ask that you will realize that the main substance burned by the brain is glucose. The dominant form of metabolism in the nervous system is connected with the breakdown of glucose and lactic acid, and this can be proved by experiment in the living animal and with brain-tissue in vitro. In doing experiments we are not able to carry out work with human brain, because we cannot get human tissue fresh enough, so we have to carry out experiments with animals. They are carried out in this way. We cut slices of the cortex of the brain as soon as the animal is dead, that is to say, within ten minutes of death the brain is out and slices have been cut. They are placed in a physiological medium in the presence of glucose, and we follow the metabolism of that tissue, which allows us to estimate the amount of oxygen being taken up by the brain. If luminal, chloretone, hyoscine or somnifaine be placed with the brain-tissue, then the respiration, instead of being at the usual level, starts lower down, and maintains a straight line. We wanted to see whether this action is reversible or irreversible. If the latter, then on removing the brain-slices from the narcotic it should no longer behave like a normal piece of tissue. Actually, when the brain-slice is removed and placed in Ringer solution, with no narcotic, the respiration goes up and becomes equal to that shown by the slice which had no narcotic. That is to say, the process is reversible.

Abstract P109: Activation Of Hypothalamic Glutamate Receptors Is Required For Angiotensin II-elicited Hypertensive Response Sensitization (HTRS) In Rats

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Baojian Xue ◽  
Hua Zhang ◽  
Terry Beltz ◽  
De-Pei Li ◽  
Alan Johnson
Keyword(s):  
Glutamate Receptors ◽  
Brain Slices ◽  
Renin Angiotensin System ◽  
Retrograde Transport ◽  
Ventrolateral Medulla ◽  
Ang Ii ◽  
Excitatory Effect ◽  
Functional Studies ◽  
Pre Treatment

Hypertension is associated with sympathetic nervous system activation, which involves interactions between the renin-angiotensin system and glutamatergic mechanisms in the hypothalamic paraventricular nucleus (PVN). Using the Induction-Delay-Expression (IND-DEL-EXP) experimental paradigm, our previous studies demonstrated that administration of a subpressor dose of angiotensin (ANG) II (10 ng/kg/min) during IND sensitizes subsequent ANG II (120 ng/kg/min)-elicited hypertension during EXP. Systemic or intracerebroventricular administration of glutamatergic NMDA-R antagonists (MK801 and AP5) during the IND period abolishes the IND of ANG II-elicited hypertensive response sensitization (HTRS). In the present study, we investigated further the role of hypothalamic glutamate and glutamate receptors (GluRs) in ANG II-elicited HTRS. First, PVN neurons to be studied in vitro were back-labelled by a tracer injected into the rostral ventrolateral medulla (RVLM). After sufficient time for retrograde transport, the rats were treated with a subpressor dose of ANG II sufficient to induce HTRS. In PVN brain slices studied following DEL, basal firing activities of PVN-RVLM projecting neurons did not differ between rats treated with saline and rats treated with a subpressor dose of ANG II. However, bath application of ANG II (2.0 μM) induced a significant increase in the firing rate of PVN-RVLM neurons in rats treated with ANG II during IND as compared to saline treated controls. This enhanced excitatory effect of ANG II on PVN-RVLM neurons was blocked by an NMDAR antagonist, AP5 (50 μM). Pre-treatment with the subpressor dose of ANG II during IND also significantly increased evoked NMDAR- excitatory postsynaptic currents in PVN-RVLM neurons. In functional studies, we found that bilateral PVN microinjections of glutamate (100 nm, 100 nl) during IND produced HTRS whereas PVN vehicle injections did not (Δ50.8±3.2 vs Δ20.8±6.5 mmHg). Taken together, our findings indicate that GluR activation in the PVN is sufficient and necessary for the IND of ANG II-elicited HTRS. The results indicate that a sustained increase in excitability of PVN-RVLM projecting neurons is likely to play an important role in maintaining the CNS state that produces HTRS.

scholarly journals Amyloid β Peptide-Induced Changes in Prefrontal Cortex Activity and Its Response to Hippocampal Input

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Ernesto Flores-Martínez ◽  
Fernando Peña-Ortega
Keyword(s):  
Prefrontal Cortex ◽  
Brain Slices ◽  
Amyloid Β ◽  
Network Activity ◽  
Amyloid Β Peptide ◽  
Cell Level ◽  
Long Range Interactions ◽  
Induced Changes ◽  
The Brain

Alterations in prefrontal cortex (PFC) function and abnormalities in its interactions with other brain areas (i.e., the hippocampus) have been related to Alzheimer Disease (AD). Considering that these malfunctions correlate with the increase in the brain’s amyloid beta (Aβ) peptide production, here we looked for a causal relationship between these pathognomonic signs of AD. Thus, we tested whether or not Aβ affects the activity of the PFC network and the activation of this cortex by hippocampal input stimulation in vitro. We found that Aβ application to brain slices inhibits PFC spontaneous network activity as well as PFC activation, both at the population and at the single-cell level, when the hippocampal input is stimulated. Our data suggest that Aβ can contribute to AD by disrupting PFC activity and its long-range interactions throughout the brain.

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