Heptanol But Not Fluoroacetate Prevents the Propagation of Spreading Depression in Rat Hippocampal Slices

1997 ◽  
Vol 77 (1) ◽  
pp. 9-16 ◽  
Author(s):  
Carlota Largo ◽  
Geoffrey C. Tombaugh ◽  
Peter G. Aitken ◽  
Oscar Herreras ◽  
George G. Somjen
Keyword(s):  
Synaptic Transmission ◽  
Gap Junctions ◽  
Spreading Depression ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Lipid Phase ◽  
Tissue Slices ◽  
Population Spikes ◽  
Afferent Volleys ◽  
Stimulation Of

Largo, Carlota, Geoffrey C. Tombaugh, Peter G. Aitken, Oscar Herreras, and George G. Somjen. Heptanol but not fluoroacetate prevents the propagation of spreading depression in rat hippocampal slices. J. Neurophysiol. 77: 9–16, 1997. We investigated whether heptanol and other long-chain alcohols that are known to block gap junctions interfere with the generation or the propagation of spreading depression (SD). Waves of SD were triggered by micro-injection of concentrated KCl solution in stratum (s.) radiatum of CA1 of rat hippocampal tissue slices. DC-coupled recordings of extracellular potential ( V o) were made at the injection and at a second site ∼1 mm distant in st. radiatum and sometimes also in st. pyramidale. Extracellular excitatory postsynaptic potentials (fEPSPs) were evoked by stimulation of the Schaffer collateral bundle; in some experiments, antidromic population spikes were evoked by stimulation of the alveus. Bath application of 3 mM heptanol or 5 mM hexanol completely and reversibly prevented the propagation of the SD-related potential shift (Δ V o) without abolishing the Δ V o at the injection site. Octanol (1 mM) had a similar but less reliably reversible effect. fEPSPs were depressed by ∼30% by heptanol and octanol, 65% by hexanol. Antidromic population spikes were depressed by 30%. In isolated, patch-clamped CA1 pyramidal neurons, heptanol partially and reversibly depressed voltage-dependent Na currents possibly explaining the slight depression of antidromic spikes and, by acting on presynaptic action potentials, also the depression of fEPSPs. Fluoroacetate (FAc), a putative selective blocker of glial metabolism, first induced multiple spike firing in response to single afferent volleys and then severely suppressed synaptic transmission (confirming earlier reports) without depressing the antidromic population spike. FAc did not inhibit SD propagation. The effect of alkyl alcohols is compatible with the idea that the opening of normally closed neuronal gap junctions is required for SD propagation. Alternative possible explanations include interference with the lipid phase of neuron membranes. The absence of SD inhibition by FAc confirms that synaptic transmission is not necessary for the propagation of SD, and it suggests that normally functioning glial cells are not essential for SD generation or propagation.

Two Mechanisms That Raise Free Intracellular Calcium in Rat Hippocampal Neurons During Hypoosmotic and Low NaCl Treatment

2000 ◽  
Vol 83 (1) ◽  
pp. 81-89 ◽  
Author(s):  
Aren J. Borgdorff ◽  
George G. Somjen ◽  
Wytse J. Wadman
Keyword(s):  
Synaptic Transmission ◽  
Intracellular Calcium ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Cell Swelling ◽  
Tissue Slices ◽  
Extracellular Medium ◽  
Calcium Activity ◽  
Hippocampal Pyramidal Neurons

Previous studies have shown that exposing hippocampal slices to low osmolarity (πo) or to low extracellular NaCl concentration ([NaCl]o) enhances synaptic transmission and also causes interstitial calcium ([Ca2+]o) to decrease. Reduction of [Ca2+]o suggests cellular uptake and could explain the potentiation of synaptic transmission. We measured intracellular calcium activity ([Ca2+]i) using fluorescent indicator dyes. In CA1 hippocampal pyramidal neurons in tissue slices, lowering πo by ∼70 mOsm caused “resting” [Ca2+]i as well as synaptically or directly stimulated transient increases of calcium activity (Δ[Ca2+]i) to transiently decrease and then to increase. In dissociated cells, lowering πo by ∼70 mOsm caused [Ca2+]i to almost double on average from 83 to 155 nM. The increase of [Ca2+]i was not significantly correlated with hypotonic cell swelling. Isoosmotic (mannitol- or sucrose-substituted) lowering of [NaCl]o, which did not cause cell swelling, also raised [Ca2+]i. Substituting NaCl with choline-Cl or Na-methyl-sulfate did not affect [Ca2+]i. In neurons bathed in calcium-free medium, lowering πo caused a milder increase of [Ca2+]i, which was correlated with cell swelling, but in the absence of external Ca2+, isotonic lowering of [NaCl]o triggered only a brief, transient response. We conclude that decrease of extracellular ionic strength (i.e., in both low πo and low [NaCl]o) causes a net influx of Ca2+ from the extracellular medium whereas cell swelling, or the increase in membrane tension, is a signal for the release of Ca2+ from intracellular stores.

scholarly journals KCNQ/Kv7 Channel Regulation of Hippocampal Gamma-Frequency Firing in the Absence of Synaptic Transmission

2006 ◽  
Vol 95 (5) ◽  
pp. 3105-3112 ◽  
Author(s):  
S. Piccinin ◽  
A. D. Randall ◽  
J. T. Brown
Keyword(s):  
Synaptic Transmission ◽  
High Frequency ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Neuronal Firing ◽  
Population Spike ◽  
Channel Blockers ◽  
Kv7 Channels ◽  
Population Spikes ◽  
Gamma Frequency

Synchronous neuronal firing can be induced in hippocampal slices in the absence of synaptic transmission by lowering extracellular Ca2+ and raising extracellular K+. However, the ionic mechanisms underlying this nonsynaptic synchronous firing are not well understood. In this study we have investigated the role of KCNQ /Kv7 channels in regulating this form of nonsynaptic bursting activity. Incubation of rat hippocampal slices in reduced (<0.2 mM) [Ca2+]o and increased (6.3 mM) [K+]o, blocked synaptic transmission, increased neuronal firing, and led to the development of spontaneous periodic nonsynaptic epileptiform activity. This activity was recorded extracellularly as large (4.7 ± 1.9 mV) depolarizing envelopes with superimposed high-frequency synchronous population spikes. These intraburst population spikes initially occurred at a high frequency (about 120 Hz), which decayed throughout the burst stabilizing in the gamma-frequency band (30–80 Hz). Further increasing [K+]o resulted in an increase in the interburst frequency without altering the intraburst population spike frequency. Application of retigabine (10 μM), a Kv7 channel modulator, completely abolished the bursts, in an XE-991–sensitive manner. Furthermore, application of the Kv7 channel blockers, linopirdine (10 μM) or XE-991 (10 μM) alone, abolished the gamma frequency, but not the higher-frequency population spike firing observed during low Ca2+/high K+ bursts. These data suggest that Kv7 channels are likely to play a role in the regulation of synchronous population firing activity.

Enhancement of Whole Cell Synaptic Currents by Low Osmolarity and by Low [NaCl] in Rat Hippocampal Slices

1997 ◽  
Vol 77 (5) ◽  
pp. 2349-2359 ◽  
Author(s):  
Rong Huang ◽  
Daniel F. Bossut ◽  
George G. Somjen
Keyword(s):  
Synaptic Transmission ◽  
Time Constant ◽  
Hippocampal Slices ◽  
Input Resistance ◽  
Tissue Slices ◽  
Synaptic Currents ◽  
Whole Cell ◽  
Input Capacitance ◽  
Postsynaptic Currents ◽  
Inward Currents

Huang, Rong, Daniel F. Bossut, and George G. Somjen. Enhancement of whole cell synaptic currents by low osmolarity and by low [NaCl] in rat hippocampal slices. J. Neurophysiol. 77: 2349–2359, 1997. We recorded whole cell currents of patch-clamped neurons in stratum pyramidale of CA1 region of rat hippocampal tissue slices. Synaptic currents were evoked by orthodromic stimulation while holding potential of the neuron was varied from hyperpolarized to depolarized levels. Extracellular osmolarity (πo) was lowered by superfusion with artificial cerebrospinal fluid in which NaCl concentration ([NaCl]) was reduced. The effect of low extracellular NaCl was tested in additional trials in which NaCl was substituted by isosmolar fructose. Both lowering of πo and isosmotic lowering of extracellular [NaCl] ([NaCl]o) caused reversible increase of excitatory postsynaptic currents. The effect of lowering πo was concentration dependent, and it was significantly stronger than the effect of equivalent isosmotic lowering of [NaCl]o. Inhibitory postsynaptic currents also increased in many but not in all cases. Lowering of πo caused a prolongation of the time constant of relaxation of the capacitive charging current induced by small hyperpolarizing voltage steps. A virtual input capacitance, calculated by dividing this time constant by the input resistance, increased during hypotonic exposure. Isosmotic lowering of [NaCl]o had no effect on time constant or input capacitance. Depolarizing voltage commands evoked spikelike inward currents presumably representing Na+-dependent action potentials generated outside the voltage-clamped region of the cell. These current spikes became smaller in low πo and in low [NaCl]o. Broader, voltage-dependent, presumably Ca2+-mediated inward currents became more prominent during hypotonic exposure. We conclude that lowering of [NaCl]o causes enhancement of excitatory synaptic transmission. Transmission may be facilitated by the uptake of Ca2+ into presynaptic terminals as well as into postsynaptic target neurons, induced by the low [NaCl]o. Lowering of πo enhances synaptic transmission more than does a corresponding isosmotic lowering of [NaCl]. The excess increase recorded from the cell soma in low πo may in part be due to changing electrotonic length caused by the swelling of dendrites.

The involvement of nonspiking cells in long-term potentiation of synaptic transmission in the hippocampus

1988 ◽  
Vol 66 (6) ◽  
pp. 841-844 ◽  
Author(s):  
B. R. Sastry ◽  
J. W. Goh ◽  
P. B. Y. May ◽  
S. S. Chirwa
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Stratum Radiatum ◽  
Ca1 Pyramidal Neurons ◽  
Term Potentiation ◽  
Ca1 Area ◽  
Glial Depolarization ◽  
Stimulation Of

In guinea pig hippocampal slices, stimulation of stratum radiatum during depolarization (with intracellular current injections) of nonspiking cells (presumed to be glia) in the apical dendritic area of CA1 pyramidal neurons resulted in a subsequent long-term potentiation of intracellularly recorded excitatory postsynaptic potentials as well as extracellularly recorded population spikes in the CA1 area. Tetanic stimulation of stratum radiatum resulted in a subsequent prolonged depolarization of the presumed glial cells, and this depolarization was smaller when the tetanus was given during the presence of 2-amino-5-phosphonovalerate or when the slices were exposed to Ca2+-free medium containing Mn2+ and Mg2+. These results suggest that glial depolarization is involved as one of the steps in generating long-term potentiation.

Ca2+ release from intracellular stores induced by afferent stimulation of CA3 pyramidal neurons in hippocampal slices

1996 ◽  
Vol 76 (1) ◽  
pp. 554-562 ◽  
Author(s):  
L. D. Miller ◽  
J. J. Petrozzino ◽  
G. Golarai ◽  
J. A. Connor
Keyword(s):  
Receptor Antagonist ◽  
Hippocampal Slice ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Mk 801 ◽  
Fura 2 ◽  
Hippocampal Slice Cultures ◽  
Ca3 Pyramidal Neurons ◽  
Dextran Conjugate ◽  
Stimulation Of

1. Ca2+ imaging and simultaneous intracellular recording were performed on CA3 pyramidal neurons in hippocampal slice cultures and standard acute slices. Both fura-2 and a dextran conjugate of fura-2 (MW = 10,000) were used in the Ca2+ measurements to control for compartmentalization artifacts. Experiments were performed under conditions giving minimal ligand- and voltagegated Ca2+ influx, with the use of competitive and noncompetitive antagonists of ionotropic glutamate receptors and steady-state depolarization, respectively. 2. Tetanic stimulation of stratum lucidum evoked dendritic Ca2+ transients with rapid onset that were blocked by the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 (2-5 microM), but not by the competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10-50 microM). Zn(2+)-containing mossy fiber terminals (assessed by Timm's staining) and postsynaptic structures (thorny excrescences) are preserved in s. lucidum of hippocampal slice cultures. 3. A Ca2+ store loading protocol, consisting of brief repolarizations followed by steady depolarization, primed most of the neurons so that a subsequent tetanus gave a Ca2+ increase in the presence of MK-801 that was reported by both fura-2 and the dextran conjugate. The onset of the Ca2+ increase was significantly delayed (by 2-3 s) with respect to the MK-801-sensitive increase, and often had a different spatial pattern within the neuron. Response characteristics were similar in slice cultures and acute slices. 4. The delayed Ca2+ increase showed a steep rundown with subsequent stimuli, but was restored by further priming by the Ca2+ store loading paradigm. Postsynaptic currents evoked by the tetani under these conditions were not correlated with the magnitude of the delayed Ca2+ transients. 5. Delayed Ca2+ increases were observed in 44% of the neurons dialyzed with normal intracellular solution at room temperature. The success rate of observing delayed Ca2+ transients was increased to 86% in neurons maintained at 30 degrees C, and dialyzed with an inhibitor of the inositol-triphosphate-3-kinase. 6. The delayed Ca2+ transients could not be initiated after inhibition of endosomal Ca(2+)-ATPase-mediated uptake by thapsigargin. 7. Both fura-2 and the dextran conjugate reported increases in resting Ca2+ levels after the loading protocols, that were absent after priming in thapsigargin, and decreases in resting Ca2+ levels after successive tetani in MK-801, suggesting that the Ca2+ changes were largely cytosolic. 8. The present results support the hypothesis that these synaptically mediated, delayed Ca2+ transients represent release from intracellular Ca2+ stores that can be loaded and depleted repeatedly, and are evoked by presynaptic release of endogenous neurotransmitter.

scholarly journals Anti-Müllerian Hormone Regulation of Synaptic Transmission in the Hippocampus Requires MAPK Signaling and Kv4.2 Potassium Channel Activity

2021 ◽  
Vol 15 ◽  
Author(s):  
Kang Wang ◽  
Fuhua Xu ◽  
James Maylie ◽  
Jing Xu
Keyword(s):  
Synaptic Transmission ◽  
P38 Mapk ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Hormone Regulation ◽  
Paracrine Factor ◽  
Specific Expression ◽  
Hippocampal Pyramidal Neurons

Anti-Müllerian hormone (AMH) is a paracrine factor generated peripherally by the gonads to regulate gonadal function in adult mammals. We recently reported that AMH and AMH-specific receptor Anti-Müllerian hormone receptor 2 (AMHR2) are expressed in the hippocampus, and exogenous AMH protein rapidly increased synaptic transmission and long-term synaptic plasticity at the CA3-CA1 synapses. Here we examined the cell-specific expression of AMHR2 and the cellular mechanism of rapid boosting effect of AMH on synaptic transmission in mouse hippocampus. Immunofluorescence staining showed that AMHR2 was specifically expressed in the soma and dendrites of hippocampal pyramidal neurons, but not glial cells. Electrophysiological recordings on acute hippocampal slices showed that AMH did not affect AMPAR-mediated or N-Methyl-D-aspartic acid receptor (NMDAR)-mediated excitatory postsynaptic currents at the CA3-CA1 synapses. The small-conductance Ca2+-activated K+ channel (SK2) and A-type K+ channel (Kv4.2) contribute to shaping excitatory postsynaptic potentials (EPSPs) at the CA3-CA1 synapses. Bath application of apamin to block SK2 did not alter AMH effect on increasing EPSPs, whereas blocking Kv4.2 channel with 4-aminopyridine, or chelating internal Ca2+ with BAPTA occluded the action of AMH on boosting EPSPs. Kv4.2 activity is regulated by p38 mitogen-activated kinase (MAPK). Blocking p38 MAPK with SB203580 occluded the effect of AMH on increasing EPSPs. These results show that Kv4.2 channel contributes to the rapid action of AMH on boosting synaptic transmission in a Ca2+- and p38 MAPK-dependent manner. Our findings provide functional evidence that AMH enhances synaptic transmission through Kv4.2 channel in the hippocampus, suggesting a possible role of Kv4.2 channel in AMH-regulated neuronal process underlying learning and memory.

scholarly journals ALLN rescues an in vitro excitatory synaptic transmission deficit in Lis1 mutant mice

2013 ◽  
Vol 109 (2) ◽  
pp. 429-436 ◽  
Author(s):  
Joy Y. Sebe ◽  
Marina Bershteyn ◽  
Shinji Hirotsune ◽  
Anthony Wynshaw-Boris ◽  
Scott C. Baraban
Keyword(s):  
Synaptic Transmission ◽  
Neuronal Migration ◽  
Therapeutic Potential ◽  
Hippocampal Slices ◽  
In Utero ◽  
Mutant Mice ◽  
Excitatory Synaptic Transmission ◽  
Calpain Inhibitor ◽  
Tissue Slices ◽  
Littermate Control

LIS1 gene mutations lead to a rare neurological disorder, classical lissencephaly, characterized by brain malformations, mental retardation, seizures, and premature death. Mice heterozygous for Lis1 ( Lis1+/−) exhibit cortical malformations, defects in neuronal migration, increased glutamate-mediated synaptic transmission, and spontaneous electrographic seizures. Recent work demonstrated that in utero treatment of Lis1+/− mutant dams with ALLN, a calpain inhibitor, partially rescues neuronal migration defects in the offspring. Given the challenges of in utero drug administration, we examined the therapeutic potential of ALLN on postnatal lissencephalic cells. Voltage- and current-clamp studies were performed with acute hippocampal slices obtained from Lis1 mutant mice and age-matched littermate control mice. Specifically, we determined whether postnatal ALLN treatment can reverse excitatory synaptic transmission deficits, namely, an increase in spontaneous and miniature excitatory postsynaptic current (EPSC) frequency, on CA1 pyramidal neurons observed in tissue slices from Lis1+/− mice. We found that acute application of ALLN restored spontaneous and miniature EPSC frequencies to wild-type levels without affecting inhibitory postsynaptic synaptic current. Furthermore, Western blot analysis of protein expression, including proteins involved in excitatory synaptic transmission, demonstrated that ALLN blocks the cleavage of the calpain substrate αII-spectrin but does not rescue Lis1 protein levels in Lis1+/− mutants.

Maternal infection and fever during late gestation are associated with altered synaptic transmission in the hippocampus of juvenile offspring rats

2008 ◽  
Vol 295 (5) ◽  
pp. R1563-R1571 ◽  
Author(s):  
Germaine C. Lowe ◽  
Giamal N. Luheshi ◽  
Sylvain Williams
Keyword(s):  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Late Gestation ◽  
Maternal Infection ◽  
Term Potentiation ◽  
Increased Risk ◽  
Near Term

Prenatal exposure to infection is known to affect brain development and has been linked to increased risk for schizophrenia. The goal of this study was to investigate whether maternal infection and associated fever near term disrupts synaptic transmission in the hippocampus of the offspring. We used LPS to mimic bacterial infection and trigger the maternal inflammatory response in near-term rats. LPS was administered to rats on embryonic days 15 and 16 and hippocampal synaptic transmission was evaluated in the offspring on postnatal days 20–25. Only offspring from rats that showed a fever in response to LPS were tested. Schaffer collateral-evoked field excitatory postsynaptic potentials (fEPSPs) and fiber volleys in CA1 of hippocampal slices appeared smaller in offspring from the LPS group compared with controls, but, when the fEPSPs were normalized to the amplitude of fiber volleys, they were larger in the LPS group. In addition, intrinsic excitability of CA1 pyramidal neurons was heightened, as antidromic field responses in the LPS group were greater than those from control. Short-, but not long-term plasticity was impaired since paired-pulse facilitation of the fEPSP was attenuated in the LPS group, whereas no differences in long-term potentiation were noted. These results suggest that LPS-induced inflammation during pregnancy produces in the offspring a reduction in presynaptic input to CA1 with compensatory enhancements in postsynaptic glutamatergic response and pyramidal cell excitability. Neurodevelopmental disruption triggered by prenatal infection can have profound effects on hippocampal synaptic transmission, likely contributing to the memory and cognitive deficits observed in schizophrenia.

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