scholarly journals Excitatory effect of biphasic kHz field stimulation on CA1 pyramidal neurons in slices

2021 ◽  
Author(s):  
Sergei Karnup ◽  
William C. DeGroat ◽  
Jonathan M. Beckel ◽  
Changfeng Tai
Keyword(s):  
Electric Fields ◽  
Brain Slice ◽  
Pyramidal Neurons ◽  
Field Application ◽  
Neuronal Membrane ◽  
Field Stimulation ◽  
Spontaneous Firing ◽  
Excitatory Effect ◽  
Glutamatergic Synaptic Transmission ◽  
Inhibitory Synaptic Input

Background: Electrical stimulation in the kilohertz-frequency range has been successfully used for treatment of various neurological disorders. Nevertheless, the mechanisms underlying this stimulation are poorly understood. Objective: To study the effect of kilohertz-frequency electric fields on neuronal membrane biophysics we developed a reliable experimental method to measure responses of single neurons to kilohertz field stimulation in brain slice preparations. Methods: In the submerged brain slice pyramidal neurons of the CA1 subfield were recorded in the whole-cell configuration before, during and after stimulation with an external electric field at 2kHz, 5kHz or 10 kHz. Results: Reproducible excitatory changes in rheobase and spontaneous firing were elicited during kHz-field application at all stimulating frequencies. The rheobase only decreased and spontaneous firing either was initiated in silent neurons or became more intense in previously spontaneously active neurons. Response thresholds were higher at higher frequencies. Blockade of glutamatergic synaptic transmission did not alter the magnitude of responses. Inhibitory synaptic input was not changed by kilohertz field stimulation. Conclusion: kHz-frequency current applied in brain tissue has an excitatory effect on pyramidal neurons during stimulation. This effect is more prominent and occurs at a lower stimulus intensity at a frequency of 2kHz as compared to 5kHz and 10kHz.

scholarly journals Effects of Specific Electric Field Stimulation on the Release and Activity of Secreted Acid Phosphatases from Leishmania tarentolae and Implications for Therapy

Pathogens ◽  
2018 ◽  
Vol 7 (4) ◽  
pp. 77 ◽  
Author(s):  
Benjamin Dorsey ◽  
Cynthia Cass ◽  
David Cedeño ◽  
Ricardo Vallejo ◽  
Marjorie Jones
Keyword(s):  
Electric Field ◽  
Electric Fields ◽  
Field Application ◽  
Kinetic Constants ◽  
Sand Fly ◽  
Field Stimulation ◽  
Acid Phosphatases ◽  
Cell Secretion ◽  
Leishmania Tarentolae ◽  
Enzyme Isoforms

Leishmaniasis is a neglected tropical disease with 1.6 million new cases reported each year. However, there are few safe, effective, and affordable treatments provided to those affected by this disease. Still under-appreciated as potential pharmaceutical targets, especially for cutaneous leishmaniasis infections, are the two isozymes of secreted acid phosphatase (SAP). These enzymes are involved in the survival of the parasite in the sand fly vector, and in infecting host macrophages. While the application of electric or electromagnetic fields as a medicinal therapeutic is not new, the utility of electric field application for the treatment of leishmaniasis is under studied. Studies involving the effects of electric fields on the cell secretion of SAP or the activity of SAP that has been secreted prior to electrical stimulation have not yet been reported. This work is the first report on the effect of specific electric fields on the activity of Leishmania tarentolae secreted acid phosphatases and the modulation of this secretion from the cells. In addition, the kinetic constants for the enzyme isoforms were determined as a function of days in culture and removal of carbohydrate from the glycosylated enzymes, while using a glycosidase, was shown to affect these kinetic constants.

Domoic acid, the alleged "mussel toxin," might produce its neurotoxic effect through kainate receptor activation: an electrophysiological study in the rat dorsal hippocampus

1989 ◽  
Vol 67 (1) ◽  
pp. 29-33 ◽  
Author(s):  
Guy Debonnel ◽  
Luc Beauchesne ◽  
Claude de Montigny
Keyword(s):  
Amino Acid ◽  
Domoic Acid ◽  
Pyramidal Neurons ◽  
Excitatory Amino Acid ◽  
Dorsal Hippocampus ◽  
Electrophysiological Study ◽  
Receptor Activation ◽  
Kainate Receptor ◽  
Neurotoxic Effect ◽  
Excitatory Effect

Domoic acid, an excitatory amino acid structurally related to kainate, was recently identified as being presumably responsible for the recent severe intoxication presented by more than 100 people having eaten mussels grown in Prince Edward Island (Canada). The amino acid kainate has been shown to be highly neurotoxic to the hippocampus, which is the most sensitive structure in the central nervous system. The present in vivo electrophysiological studies were undertaken to determine if domoic acid exerts its neurotoxic effect via kainate receptor activation. Unitary extracellular recordings were obtained from pyramidal neurons of the CA1 and the CA3 regions of the rat dorsal hippocampus. The excitatory effect of domoic acid applied by microiontophoresis was compared with that of agonists of the three subtypes of glutamatergic receptors: kainate, quisqualate, and N-methyl-D-aspartate. In CA1, the activation induced by domoic acid was about threefold greater than that induced by kainate; identical concentrations and similar currents were used. In CA3, domoic acid was also three times more potent than kainate. However, the most striking finding was that domoic acid, similar to kainate, was more than 20-fold more potent in the CA3 than in the CA1 region, whereas no such regional difference could be detected with quisqualate and N-methyl-D-aspartate. As the differential regional response of CA1 and CA3 pyramidal neurons to kainate is attributable to the extremely high density of kainate receptors in the CA3 region, these results provide the first electrophysiological evidence that domoic acid may produce its neurotoxic effects through kainate receptor activation.Key words: domoate, kainate, excitotoxin, hippocampus, N-methyl-D-aspartate.

Resting and Active Properties of Pyramidal Neurons in Subiculum and CA1 of Rat Hippocampus

2000 ◽  
Vol 84 (5) ◽  
pp. 2398-2408 ◽  
Author(s):  
Nathan P. Staff ◽  
Hae-Yoon Jung ◽  
Tara Thiagarajan ◽  
Michael Yao ◽  
Nelson Spruston
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Pyramidal Neurons ◽  
Current Injection ◽  
Synaptic Integration ◽  
Membrane Properties ◽  
Neuronal Membrane ◽  
Similar Action ◽  
Ca1 Neurons ◽  
Ca1 Pyramidal Neurons

Action potentials are the end product of synaptic integration, a process influenced by resting and active neuronal membrane properties. Diversity in these properties contributes to specialized mechanisms of synaptic integration and action potential firing, which are likely to be of functional significance within neural circuits. In the hippocampus, the majority of subicular pyramidal neurons fire high-frequency bursts of action potentials, whereas CA1 pyramidal neurons exhibit regular spiking behavior when subjected to direct somatic current injection. Using patch-clamp recordings from morphologically identified neurons in hippocampal slices, we analyzed and compared the resting and active membrane properties of pyramidal neurons in the subiculum and CA1 regions of the hippocampus. In response to direct somatic current injection, three subicular firing types were identified (regular spiking, weak bursting, and strong bursting), while all CA1 neurons were regular spiking. Within subiculum strong bursting neurons were found preferentially further away from the CA1 subregion. Input resistance ( R N), membrane time constant (τm), and depolarizing “sag” in response to hyperpolarizing current pulses were similar in all subicular neurons, while R N and τm were significantly larger in CA1 neurons. The first spike of all subicular neurons exhibited similar action potential properties; CA1 action potentials exhibited faster rising rates, greater amplitudes, and wider half-widths than subicular action potentials. Therefore both the resting and active properties of CA1 pyramidal neurons are distinct from those of subicular neurons, which form a related class of neurons, differing in their propensity to burst. We also found that both regular spiking subicular and CA1 neurons could be transformed into a burst firing mode by application of a low concentration of 4-aminopyridine, suggesting that in both hippocampal subfields, firing properties are regulated by a slowly inactivating, D-type potassium current. The ability of all subicular pyramidal neurons to burst strengthens the notion that they form a single neuronal class, sharing a burst generating mechanism that is stronger in some cells than others.

Specificity in the Interaction of HVA Ca2+ Channel Types With Ca2+-Dependent AHPs and Firing Behavior in Neocortical Pyramidal Neurons

1998 ◽  
Vol 79 (5) ◽  
pp. 2522-2534 ◽  
Author(s):  
Juan Carlos Pineda ◽  
Robert S. Waters ◽  
Robert C. Foehring
Keyword(s):  
Brain Slice ◽  
Pyramidal Neurons ◽  
Repetitive Firing ◽  
Channel Blockers ◽  
Firing Behavior ◽  
Inward Currents ◽  
Functional Consequences ◽  
P Type ◽  
Brain Slice Preparation ◽  
Neocortical Pyramidal Neurons

Pineda, Juan Carlos, Roberts S. Waters, and Robert C. Foehring. Specificity in the interaction of HVA Ca2+ channel types with Ca2+-dependent AHPs and firing behavior in neocortical pyramidal neurons. J. Neurophysiol. 79: 2522–2534, 1998. Intracellular recordings and organic and inorganic Ca2+ channel blockers were used in a neocortical brain slice preparation to test whether high-voltage–activated (HVA) Ca2+ channels are differentially coupled to Ca2+-dependent afterhyperpolarizations (AHPs) in sensorimotor neocortical pyramidal neurons. For the most part, spike repolarization was not Ca2+ dependent in these cells, although the final phase of repolarization (after the fast AHP) was sensitive to block of N-type current. Between 30 and 60% of the medium afterhyperpolarization (mAHP) and between ∼80 and 90% of the slow AHP (sAHP) were Ca2+ dependent. Based on the effects of specific organic Ca2+ channel blockers (dihydropyridines, ω-conotoxin GVIA, ω-agatoxin IVA, and ω-conotoxin MVIIC), the sAHP is coupled to N-, P-, and Q-type currents. P-type currents were coupled to the mAHP. L-type current was not involved in the generation of either AHP but (with other HVA currents) contributes to the inward currents that regulate interspike intervals during repetitive firing. These data suggest different functional consequences for modulation of Ca2+ current subtypes.

scholarly journals Cholecystokinin Octapeptide Increases Spontaneous Glutamatergic Synaptic Transmission to Neurons of the Nucleus Tractus Solitarius Centralis

2005 ◽  
Vol 94 (4) ◽  
pp. 2763-2771 ◽  
Author(s):  
V. Baptista ◽  
Z. L. Zheng ◽  
F. H. Coleman ◽  
R. C. Rogers ◽  
R. A. Travagli
Keyword(s):  
Receptor Antagonist ◽  
Nucleus Tractus Solitarius ◽  
Dependent Manner ◽  
Excitatory Effect ◽  
Concentration Dependent Manner ◽  
Whole Cell Patch Clamp ◽  
Glutamatergic Synaptic Transmission ◽  
Immunohistochemical Techniques ◽  
20 Nm ◽  
Brain Stem Slices

Cholecystokinin (CCK) is released from enteroendocrine cells after ingestion of nutrients and induces multiple effects along the gastrointestinal tract, including gastric relaxation and short-term satiety. We used whole cell patch-clamp and immunohistochemical techniques in rat brain stem slices to characterize the effects of CCK. In 45% of the neurons of nucleus tractus solitarius subnucleus centralis (cNTS), perfusion with the sulfated form of CCK (CCK-8s) increased the frequency of spontaneous excitatory currents (sEPSCs) in a concentration-dependent manner (1–300 nM). The threshold for the CCK-8s excitatory effect was 1 nM, the EC50 was 20 nM, and Emax was 100 nM. The excitatory effects of CCK-8s were still present when the slices were preincubated with tetrodotoxin or bicuculline or when the recordings were conducted with Cs+ electrodes. Pretreatment with the CCK-A receptor antagonist, lorglumide (1 μM), antagonized the effects of CCK-8s, whereas perfusion with the CCK-B preferring agonist CCK-8 nonsulfated (CCK-ns, 1 μM) did not affect the frequency of sEPSCs. Similarly, pretreatment with the CCK-B receptor antagonist, triglumide (1 μM), did not prevent the actions of CCK-8s. Although the majority (i.e., 76%) of CCK-8s unresponsive cNTS neurons had a bipolar somata shape and were TH-IR negative, no differences were found in either the morphological or the neurochemical phenotype of cNTS neurons responsive to CCK-8s. Our results suggest that the excitatory effects of CCK-8s on terminals impinging on a subpopulation of cNTS neurons are mediated by CCK-A receptors; these responsive neurons, however, do not have morphological or neurochemical characteristics that automatically distinguish them from nonresponsive neurons.

Calcium currents in rat entorhinal cortex layer II stellate and layer III pyramidal neurons in acute brain slice

2002 ◽  
Vol 327 (3) ◽  
pp. 153-156 ◽  
Author(s):  
Violeta Visan ◽  
Uwe Heinemann ◽  
Andriy Volynets ◽  
Wolfgang Müller
Keyword(s):  
Entorhinal Cortex ◽  
Brain Slice ◽  
Pyramidal Neurons ◽  
Calcium Currents

scholarly journals Surface charge impact in low-magnesium model of seizure in rat hippocampus

2012 ◽  
Vol 107 (1) ◽  
pp. 417-423 ◽  
Author(s):  
Dmytro Isaev ◽  
Gleb Ivanchick ◽  
Volodymyr Khmyz ◽  
Elena Isaeva ◽  
Alina Savrasova ◽  
...  
Keyword(s):  
Surface Charge ◽  
Pyramidal Neurons ◽  
Seizure Threshold ◽  
Neuronal Membrane ◽  
Voltage Sensitivity ◽  
Hippocampal Pyramidal Neurons ◽  
Low Magnesium ◽  
Initial Stage ◽  
Pyramidal Layer ◽  
Hippocampal Ca1

Putative mechanisms of induction and maintenance of seizure-like activity (SLA) in the low Mg2+ model of seizures are: facilitation of NMDA receptors and decreased surface charge screening near voltage-gated channels. We have estimated the role of such screening in the early stages of SLA development at both physiological and room temperatures. External Ca2+ and Mg2+ promote a depolarization shift of the sodium channel voltage sensitivity; when examined in hippocampal pyramidal neurons, the effect of Ca2+ was 1.4 times stronger than of Mg2+. Removing Mg2+ from the extracellular solution containing 2 mM Ca2+ induced recurrent SLA in hippocampal CA1 pyramidal layer in 67% of slices. Reduction of [Ca2+]o to 1 mM resulted in 100% appearance of recurrent SLA or continuous SLA. Both delay before seizure activity and the inter-SLA time were significantly reduced. Characteristics of seizures evoked in low Mg2+/1 mM Ca2+/3.5 K+ were similar to those obtained in low Mg2+/2 Ca2+/5mM K+, suggesting that reduction of [Ca2+]o to 1 mM is identical to the increase in [K+]o to 5 mM in terms of changes in cellular excitability and seizure threshold. An increase of [Ca2+]o to 3 mM completely abolished SLA generation even in the presence of 5 mM [K+]o. A large variation in the ability of [Ca2+]o to stop epileptic discharges in initial stage of SLA was found. Our results indicate that surface charge of the neuronal membrane plays a crucial role in the initiation of low Mg2+-induced seizures. Furthermore, our study suggests that Ca2+ and Mg2+, through screening of surface charge, have important anti-seizure and antiepileptic properties.

scholarly journals Endocannabinoid- and mGluR5-Dependent Short-Term Synaptic Depression in an Isolated Neuron/Bouton Preparation From the Hippocampal CA1 Region

2008 ◽  
Vol 100 (2) ◽  
pp. 1041-1052 ◽  
Author(s):  
Anton Sheinin ◽  
Giuseppe Talani ◽  
Margaret I. Davis ◽  
David M. Lovinger
Keyword(s):  
Hippocampal Neurons ◽  
Basolateral Amygdala ◽  
Pyramidal Neurons ◽  
Metabotropic Glutamate Receptor ◽  
Hippocampal Slices ◽  
Neuronal Membrane ◽  
Short Term ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Isolated Neuron

Endocannabinoids released from the postsynaptic neuronal membrane can activate presynaptic CB1 receptors and inhibit neurotransmitter release. In hippocampal slices, depolarization of the CA1 pyramidal neurons elicits an endocannabinoid-mediated inhibition of γ-aminobutyric acid release known as depolarization-induced suppression of inhibition (DSI). Using the highly reduced neuron/synaptic bouton preparation from the CA1 region of hippocampus, we have begun to examine endocannabinoid-dependent short-term depression (STD) of inhibitory synaptic transmission under well-controlled physiological and pharmacological conditions in an environment free of other cells. Application of the CB1 synthetic agonist WIN55212 -2 and endogenous cannabinoids 2-AG and anandamide produced a decrease in spontaneous inhibitory postsynaptic current (sIPSC) frequency and amplitude, indicating the presence of CB1 receptors at synapses in this preparation. Endocannabinoid-dependent STD is different from DSI found in hippocampal slices and the neuron/bouton preparation from basolateral amygdala (BLA) since depolarization alone was not sufficient to induce suppression of sIPSCs. However, concurrent application of the metabotropic glutamate receptor (mGluR) agonist ( RS)-3,5-dihydroxyphenylglycine (DHPG) and postsynaptic depolarization resulted in a transient (30–50 s) decrease in sIPSC frequency and amplitude. Application of DHPG alone had no effect on sIPSCs. The depolarization/DHPG-induced STD was blocked by the CB1 antagonist SR141716A and the mGluR5 antagonist MPEP and was sensitive to intracellular calcium concentration. Comparing the present findings with earlier work in hippocampal slices and BLA, it appears that endocannabinoid release is less robust in isolated hippocampal neurons.

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