Role of norepinephrine in seizurelike activity of hippocampal pyramidal cells maintained in vitro: alteration by 6-hydroxydopamine lesions of norepinephrine-containing systems

1983 ◽  
Vol 61 (8) ◽  
pp. 841-846 ◽  
Author(s):  
I. Mody ◽  
P. Leung ◽  
J. J. Miller
Keyword(s):  
Epileptiform Activity ◽  
Pyramidal Cells ◽  
Population Spike ◽  
Stratum Radiatum ◽  
Excitatory Postsynaptic Potential ◽  
Ca1 Pyramidal Cells ◽  
Ca1 Region ◽  
Population Spike Amplitude ◽  
6 Hydroxydopamine

Perfusion of 50 μM norepinephrine (NE) produced a marked, reversible decrease (range 20–28%) of the extracellular population spike and excitatory postsynaptic potential (EPSP) responses of the CA1 region evoked by stratum radiatum stimulation in the rat hippocampal slice preparation. The effects of NE were dramatically altered in slices obtained from animals which were previously treated with intracerebral or intraventricular injections of 6-hydroxydopamine (6-OHDA) to destroy forebrain catecholamine systems. In the latter preparations NE produced a reduction in the inhibition of the EPSP (50%), enhancement of the population spike amplitude, and multiple spike discharges characteristic of ongoing epileptiform activity. The reversal of NE-induced inhibition and the generation of seizurelike activity in 6-OHDA-treated animals suggests that NE may, in part, act upon interneurons to produce a disinhibition of CA1 pyramidal cells.

Dual role of norepinephrine in the hippocampal CA1 region of the rat: inhibition and disinhibition

1988 ◽  
Vol 66 (6) ◽  
pp. 814-819 ◽  
Author(s):  
Patrick P.-H. Leung ◽  
James J. Miller
Keyword(s):  
Pyramidal Neurons ◽  
Epileptiform Activity ◽  
Pyramidal Cells ◽  
Inhibitory Effect ◽  
Stratum Radiatum ◽  
Inhibitory Interneurons ◽  
Spike Response ◽  
Paired Pulse ◽  
Ca1 Region

Norepinephrine (NE) has been shown to produce either an inhibitory or an excitatory influence on CA1 pyramidal neurons of the hippocampus depending on the dosage. It was suggested that NE, in addition to exerting a direct inhibitory effect on pyramidal cells, may also act upon recurrent inhibitory interneurons to produce a disinhibition of the pyramidal cells. The present study was undertaken to examine the effect of NE on alveus-evoked inhibition, presumably mediated by the basket cell interneurons innervating the pyramidal cells. Experiments were carried out on the in vitro hippocampal slice preparation and inhibition was assessed by the percent reduction of the stratum radiatum evoked population spike response when preceded by a conditioning pulse delivered to the alveus to activate the inhibitory interneurons via the recurrent collaterals of the pyramidal cells. Paired pulse stimulation resulted in inhibition of the stratum radiatum evoked test response with conditioning-test intervals up to 60 ms. NE (50 μM) perfusion resulted in a significant and reversible reduction of the alveus-evoked recurrent inhibition. Intracellular recordings using a similar paired pulse paradigm corroborated the extracellular data well. The possible roles of NE in the physiological functioning and pathophysiology of epileptiform activity of the hippocampus are discussed.

scholarly journals Glutamatergic Propagation of GABAergic Seizure-Like Afterdischarge in the Hippocampus In Vitro

2003 ◽  
Vol 90 (4) ◽  
pp. 2746-2751 ◽  
Author(s):  
Yoshikazu Isomura ◽  
Yoko Fujiwara-Tsukamoto ◽  
Masahiko Takada
Keyword(s):  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
In Vitro Study ◽  
Pyramidal Cells ◽  
Inhibitory Effect ◽  
Experimental Models ◽  
Fluoride Ions ◽  
Ca1 Region ◽  
Cortical Regions

Previous investigations have suggested that GABA may act actively as an excitatory mediator in the generation of seizure-like (ictal) or interictal epileptiform activity in several experimental models of temporal lobe epilepsy. However, it remains to be known whether or not such GABAergic excitation may participate in seizure propagation into neighboring cortical regions. In our in vitro study using mature rat hippocampal slices, we examined the cellular mechanism underlying synchronous propagation of seizure-like afterdischarge in the CA1 region, which is driven by depolarizing GABAergic transmission, into the adjacent subiculum region. Tetanically induced seizure-like afterdischarge was always preceded by a GABAergic, slow posttetanic depolarization in the pyramidal cells of the original seizure-generating region. In contrast, the slow posttetanic depolarization was no longer observed in the subicular pyramidal cells when the afterdischarge was induced in the CA1 region. Surgical cutting of axonal pathways through the stratum oriens and the alveus between the CA1 and the subiculum region abolished the CA1-generated afterdischarge in the subicular pyramidal cells. Intracellular loading of fluoride ions, a GABAA receptor blocker, into single subicular pyramidal cells had no inhibitory effect on the CA1-generated afterdischarge in the pyramidal cells. Furthermore, the CA1-generated afterdischarge in the subicular pyramidal cells was largely depressed by local application of glutamate receptor antagonists to the subiculum region during afterdischarge generation. The present results indicate that the excitatory GABAergic generation of seizure-like activity seems to be restricted to epileptogenic foci of origin in the seizure-like epilepsy model in vitro.

Neuropeptide Y5 Receptors Reduce Synaptic Excitation in Proximal Subiculum, But Not Epileptiform Activity in Rat Hippocampal Slices

2000 ◽  
Vol 83 (2) ◽  
pp. 723-734 ◽  
Author(s):  
Melisa W. Y. Ho ◽  
Annette G. Beck-Sickinger ◽  
William F. Colmers
Keyword(s):  
In Vitro Model ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Membrane Properties ◽  
Stratum Radiatum ◽  
Synaptic Excitation ◽  
Vitro Model ◽  
Area Ca3

Neuropeptide Y (NPY) potently inhibits excitatory synaptic transmission in the hippocampus, acting predominantly via a presynaptic Y2 receptor. Recent reports that the Y5 receptor may mediate the anticonvulsant actions of NPY in vivo prompted us to test the hypothesis that Y5receptors inhibit synaptic excitation in the hippocampal slice and, furthermore, that they are effective in an in vitro model of anticonvulsant action. Two putative Y5 receptor–preferring agonists inhibited excitatory postsynaptic currents (EPSCs) evoked by stimulation of stratum radiatum in pyramidal cells. We recorded initially from area CA1 pyramidal cells, but subsequently switched to cells from the subiculum, where a much greater frequency of response was observed to Y5 agonist application. Bothd-Trp32NPY (1 μM) and [ahx8–20]Pro34NPY (3 μM), a centrally truncated, Y1/Y5 agonist we synthesized, inhibited stimulus-evoked EPSCs in subicular pyramidal cells by 44.0 ± 5.7% and 51.3 ± 3.5% (mean ± SE), in 37 and 58% of cells, respectively. By contrast, the less selective centrally truncated agonist, [ahx8–20] NPY (1 μM), was more potent (66.4 ± 4.1% inhibition) and more widely effective, suppressing the EPSC in 86% of subicular neurons. The site of action of all NPY agonists tested was most probably presynaptic, because agonist application caused no changes in postsynaptic membrane properties. The selective Y1 antagonist, BIBP3226 (1 μM), did not reduce the effect of either more selective agonist, indicating that they activated presynaptic Y5 receptors. Y5 receptor–mediated synaptic inhibition was more frequently observed in slices from younger animals, whereas the nonselective agonist appeared equally effective at all ages tested. Because of the similarity with the previously reported actions of Y2 receptors, we tested the ability of Y5receptor agonists to suppress stimulus train-induced bursting (STIB), an in vitro model of ictaform activity, in both area CA3 and the subiculum. Neither [ahx8–20]Pro34NPY nord-Trp32NPY were significantly effective in suppressing or shortening STIB-induced afterdischarge, with <20% of slices responding to these agonists in recordings from CA3 and none in subiculum. By contrast, 1 μM each of [ahx8–20]NPY, the Y2 agonist, [ahx5–24]NPY, and particularly NPY itself suppressed the afterdischarge in area CA3 and the subiculum, as reported earlier. We conclude that Y5receptors appear to regulate excitability to some degree in the subiculum of young rats, but their contribution is relatively small compared with those of Y2 receptors, declines with age, and is insufficient to block or significantly attenuate STIB-induced afterdischarges.

Blocking GABAA Inhibition Reveals AMPA- and NMDA-Receptor-Mediated Polysynaptic Responses in the CA1 Region of the Rat Hippocampus

1997 ◽  
Vol 77 (4) ◽  
pp. 2071-2082 ◽  
Author(s):  
V. Crépel ◽  
R. Khazipov ◽  
Y. Ben-Ari
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Pyramidal Cell ◽  
Pyramidal Cells ◽  
Stratum Radiatum ◽  
External Concentration ◽  
Physiological Concentration ◽  
Ca1 Pyramidal Cells ◽  
Ca1 Region ◽  
Stimulation Of

Crépel, V., R. Khazipov, and Y. Ben-Ari. Blocking GABAA inhibition reveals AMPA- and NMDA-receptor-mediated polysynaptic responses in the CA1 region of the rat hippocampus. J. Neurophysiol. 77: 2071–2082, 1997. We have investigated the conditions required to evoke polysynaptic responses in the isolated CA1 region of hippocampal slices from Wistar adult rats. Experiments were performed with extracellular and whole cell recording techniques. In the presence of bicuculline (10 μM), 6-cyano-7-nitroquinoxaline-2-3-dione (10 μM), glycine (10 μM), and a low external concentration of Mg2+ (0.3 mM), electrical stimulation of the Schaffer collaterals/commissural pathway evoked graded N-methyl-d-aspartate (NMDA)-receptor-mediated late field potentials in the stratum radiatum of the CA1 region. These responses were generated via polysynaptic connections because their latency varied strongly and inversely with the stimulation intensity and they were abolished by a high concentration of divalent cations (7 mM Ca2+). These responses likely were driven by local collateral branches of CA1 pyramidal cell axons because focal application of tetrodotoxin (30 μM) in the stratum oriens strongly reduced the late synaptic component and antidromic stimulation of CA1 pyramidal cells could evoke the polysynaptic response. Current-source density analysis suggested that the polysynaptic response was generated along the proximal part of the apical dendrites of CA1 pyramidal cells (50–150 μm below the pyramidal cell layer in the stratum radiatum). In physiological concentration of Mg2+ (1.3 mM), the pharmacologically isolated NMDA-receptor-mediated polysynaptic response was abolished. In control artificial cerebrospinal fluid (with physiological concentration of Mg2+), bicuculline (10 μM) generated a graded polysynaptic response. Under these conditions, this response was mediated both by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/NMDA receptors. In the presence of d-2-amino-5-phosphonovalerate (50 μM), the polysynaptic response could be mediated by AMPA receptors, although less efficiently. In conclusion, suppression of γ-aminobutyric acid-A inhibition reveals glutamate receptor-mediated network-driven events in the isolated CA1 region. These polysynaptic responses are mediated by AMPA and/or NMDA receptors depending on the pharmacological conditions and the external concentration of Mg2+ used. We suggest that these responses are driven by local recurrent collaterals of CA1 pyramidal cells.

Long-Lasting Increase in Cellular Excitability Associated With the Priming of LTP Induction in Rat Hippocampus

1999 ◽  
Vol 82 (6) ◽  
pp. 3139-3148 ◽  
Author(s):  
Akiva S. Cohen ◽  
Christine M. Coussens ◽  
Clarke R. Raymond ◽  
Wickliffe C. Abraham
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Long Term Potentiation ◽  
Population Spike ◽  
Metabotropic Glutamate ◽  
Ca1 Pyramidal Cells ◽  
Term Potentiation ◽  
Priming Paradigm ◽  
Population Spike Amplitude

The mechanisms underlying the facilitation (priming) of long-term potentiation (LTP) by prior activation of metabotropic glutamate receptors (mGluRs) were investigated in area CA1 of rat hippocampal slices. In particular, we focused on whether a long-lasting increase in postsynaptic excitability could account for the facilitated LTP. Administration of the mGluR agonist 1S,3R-aminocyclopentanedicarboxylic acid (ACPD) produced rapid decreases in the amplitude of both the slow spike afterhyperpolarization (AHPslow) and spike frequency adaptation recorded intracellularly from CA1 pyramidal cells. These changes persisted after drug washout, showing only a slow decay over 20 min. ACPD also caused a leftward shift of the field EPSP-population spike relation and an overall increase in population spike amplitude, but this effect was not as persistent as the intracellularly measured alterations in cell excitability. ACPD-treated cells showed increased spike discharges during LTP-inducing tetanic stimulation, and the amplitude of the AHPslow was negatively correlated with the degree of initial LTP induction. The β-adrenergic agonist isoproterenol also caused excitability changes as recorded intracellularly, whereas in extracellular experiments it weakly primed the induction but not the persistence of LTP. ACPD primed both LTP measures. Isoproterenol administration during the tetanus occluded the priming effect of ACPD on initial LTP induction but not its effect on LTP persistence. We conclude that the persistent excitability changes elicited by ACPD contributes to the priming of LTP induction but that other ACPD-triggered mechanisms must account for the facilitated persistence of LTP in the priming paradigm.

Propylparaben suppresses epileptiform activity in hippocampal CA1 pyramidal cells in vitro

2017 ◽  
Vol 136 ◽  
pp. 126-129 ◽  
Author(s):  
Leonardo Lara-Valderrábano ◽  
Emilio J. Galván ◽  
Luisa Rocha
Keyword(s):  
Epileptiform Activity ◽  
Pyramidal Cells ◽  
Ca1 Pyramidal Cells ◽  
Hippocampal Ca1

Changes in inhibitory neurotransmission in the CA1 region and dentate gyrus in a chronic model of temporal lobe epilepsy

1995 ◽  
Vol 74 (2) ◽  
pp. 829-840 ◽  
Author(s):  
P. S. Mangan ◽  
D. A. Rempe ◽  
E. W. Lothman
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Dentate Gyrus ◽  
Temporal Lobe ◽  
Granule Cells ◽  
Pyramidal Cells ◽  
Stratum Radiatum ◽  
Ca1 Pyramidal Cells ◽  
Ca1 Region ◽  
Stratum Lacunosum Moleculare ◽  
Reversal Potentials

1. In this report we compare changes in inhibitory neurotransmission within the CA1 region and the dentate gyrus (DG) in a model of chronic temporal lobe epilepsy (TLE). Extracellular and intracellular recordings were obtained in combined hippocampal-parahippocampal slices > or = 1 mo after a period of self-sustaining limbic status epilepticus (SSLSE) induced by continuous hippocampal stimulation. 2. Polysynaptic inhibitory postsynaptic potentials (IPSPs) were induced by positioning electrodes to activate specific afferent pathways and evoking responses in the absence of glutamate receptor antagonists [D(-)-2-amino-5-phosphonovaleric acid (APV) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)]. Polysynaptic IPSPs were evoked in CA1 pyramidal cells from electrodes positioned in stratum radiatum and in stratum lacunosum/moleculare. Polysynaptic IPSPs were evoked in DG granule cells from electrodes positioned over the perforant path located in the subiculum. Monosynaptic IPSPs were induced by positioning electrodes within 200 microns of the intracellular recording electrode (near site stimulation) and stimulating in the presence of APV and CNQX to block ionotropic glutamate receptors. Monosynaptic IPSPs were evoked in CA1 pyramidal cells with electrodes positioned in the stratum lacunosum/moleculare and stratum pyramidale. Monosynaptic IPSPs were evoked in DG granule cells with electrodes positioned in the stratum moleculare. 3. Population spike (PS) amplitudes were employed to assure that a full range of stimulus strengths, from subthreshold for action potentials to an intensity giving maximal-amplitude PSs, was used to elicit polysynaptic IPSPs in CA1 pyramidal cells in both post-SSLSE and control slices. In control tissue, polysynaptic IPSPs were biphasic, composed of early and late events. In post-SSLSE tissue, polysynaptic IPSPs were markedly diminished. The diminution of polysynaptic IPSPs was detected at all levels of stimulus intensity. Both early IPSPs [mediated by gamma-aminobutyric acid-A (GABAA) receptors] and late IPSPs (mediated by GABAB receptors) were diminished. Polysynaptic IPSPs were diminished with both stratum radiatum and with stratum lacunosum/moleculare stimulation. 4. Reversal potentials for either polysynaptic early or polysynaptic late IPSPs evoked in CA1 pyramidal cells by stratum radiatum stimulation were not different in slices from post-SSLSE animals as compared with control animals. Likewise, reversal potentials for either polysynaptic early or polysynaptic late IPSPs evoked by stratum lacunosum/moleculare stimulation did not differ in the two groups. These findings excluded changes in driving force as an explanation for the diminished amplitude of IPSPs in CA1 pyramidal cells in the post-SSLSE model.(ABSTRACT TRUNCATED AT 400 WORDS)

Extracellular Chloride and the Maintenance of Spontaneous Epileptiform Activity in Rat Hippocampal Slices

1999 ◽  
Vol 81 (1) ◽  
pp. 49-59 ◽  
Author(s):  
Daryl W. Hochman ◽  
Raimondo D'Ambrosio ◽  
Damir Janigro ◽  
Philip A. Schwartzkroin
Keyword(s):  
Prolonged Exposure ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Spontaneous Discharge ◽  
Extracellular Potassium ◽  
Ca1 Pyramidal Cells ◽  
Ca1 Region ◽  
Negative Field

Hochman, Daryl W., Raimondo D'Ambrosio, Damir Janigro, and Philip A. Schwartzkroin. Extracellular chloride and the maintenance of spontaneous epileptiform activity in rat hippocampal slices. J. Neurophysiol. 81: 49–59, 1999. Previous studies showed that furosemide blocks spontaneous epileptiform activity without diminishing synaptic transmission or reducing hyperexcited field responses to electrical stimuli. We now test the hypothesis that the antiepileptic effects of furosemide are mediated through its blockade of the Na+,K+,2Cl− cotransporter and thus should be mimicked by a reduction of extracellular chloride ([Cl−]o). In the first set of experiments, field recordings from the CA1 cell body layer of hippocampal slices showed that spontaneous bursting developed within 10–20 min in slices perfused with low-[Cl−]o (7 mM) medium but that this spontaneous epileptiform activity ceased after a further 10–20 min. Intracellular recordings from CA1 pyramidal cells showed that normal action potential discharge could be elicited by membrane depolarization, even after the tissue was perfused with low-[Cl−]o medium for >2 h. In a second set of experiments, spontaneous bursting activity was induced in slices by perfusion with high-[K+]o (10 mM), bicuculline (100 μM), or 4-aminopyridine (100 μM). In each case, recordings from the CA1 region showed that reduction of [Cl−]o to 21 mM reversibly blocked the bursting within 1 h. Similar to previous observations with furosemide treatment, low-[Cl−]o medium blocked spontaneous hypersynchronous discharges without reducing synaptic hyperexcitability (i.e., hyperexcitable field responses evoked by electrical stimulation). In a third set of experiments, prolonged exposure (>1 h after spontaneous bursting ceased) of slices to systematically varied [Cl−]o and [K+]o resulted in one of three types of events: 1) spontaneous, long-lasting, and repetitive negative field potential shifts (7 mM [Cl−]o; 3 mM [K+]o); 2) oscillations consisting of 5- to 10-mV negative shifts in the field potential, with a period of ∼1 cycle/40 s (16 mM [Cl−]o; 12 mM [K+]o); and 3) shorter, infrequently occurring negative field shifts lasting 20–40 s (21 mM [Cl−]o; 3 mM [K+]o). Our observations indicate that the effects of low [Cl−]o on neuronal synchronization and spontaneous discharge are time dependent. Similar effects were seen with furosemide and low [Cl−]o, consistent with the hypothesis that the antiepileptic effect of furosemide is mediated by the drug's effect on chloride transporters. Finally, the results of altering extracellular potassium along with chloride suggest that blockade of the Na+, K+,2Cl− cotransporter, which normally transports chloride from the extracellular space into glial cells, is key to these antiepileptic effects.

Osmotic effects on the CA1 neuronal population in hippocampal slices with special reference to glucose

1991 ◽  
Vol 65 (5) ◽  
pp. 1055-1066 ◽  
Author(s):  
B. A. Ballyk ◽  
S. J. Quackenbush ◽  
R. D. Andrew
Keyword(s):  
Action Potential ◽  
Single Cell ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Stratum Radiatum ◽  
Resting Potential ◽  
Excitatory Postsynaptic Potential ◽  
Stratum Pyramidale ◽  
Postsynaptic Potential ◽  
Axonal Excitability

1. Lowered osmolality promotes epileptiform activity both clinically and in the hippocampal slice preparation, but it is unclear how neurons are excited. We studied the effects of altered osmolality on the electrophysiological properties of CA1 pyramidal cells in hippocampal slices by the use of field and intracellular recordings. The excitability of these neurons under various osmotic conditions was gauged by population spike (PS) amplitude, single cell properties, and evoked synaptic input. 2. The orthodromic PS recorded in stratum pyramidale and the field excitatory postsynaptic potential (EPSP) in stratum radiatum were inversely proportional in amplitude to the artificial cerebrospinal fluid (ACSF) osmolality over a range of +/- 80 milliosmoles/kgH2O (mosM). The effect was osmotic because changes occurred within the time frame expected for cellular expansion or shrinkage and because permeable substances such as dimethyl sulfoxide or glycerol were without effect. Dilutional changes in ACSF constituents were experimentally ruled out as promoting excitability. 3. To test whether the field data resulted from a change in single-cell excitability, CA1 cells were intracellularly recorded during exposure to +/- 40 mosM ACSF over 15 min. There was no consistent effect upon CA1 resting potential, cell input resistance, or action potential threshold. 4. Osmotic alteration of orthodromic and antidromic field potentials might involve a change in axonal excitability. However, the evoked afferent volley recorded in CA1 stratum pyramidale or radiatum, which represents the compound action potential (CAP) generated in presynaptic axons, remained osmotically unresponsive with regard to amplitude, duration, or latency. This was also characteristic of CAPs evoked in isolated sciatic and vagus nerve preparations exposed to +/- 80 mosM. Therefore axonal excitability and associated extracellular current flow generated periaxonally are not significantly affected by osmotic shifts. 5. The osmotic effect on field potential amplitudes appeared to be independent of synaptic transmission because the inverse relationship with osmolality held for the antidromically evoked PS. Moreover, as recorded with respect to ground, the intracellular EPSP-inhibitory postsynaptic potential (IPSP) sequence (evoked from CA3 stratum radiatum) was not altered by osmolality. 6. The PS could occasionally be recorded intracellularly as a brief negativity interrupting the evoked EPSP. In hyposmotic ACSF, the amplitude increased and action potentials arose from the trough of the negativity as expected for a field effect. This is presumably the result of enhanced intracellular channeling of current caused by the increased extracellular resistance that accompanies cellular swelling.(ABSTRACT TRUNCATED AT 400 WORDS)

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