Inhibitory processes of hippocampal CA1 pyramidal neurons following kindling-induced epilepsy in the rat

1985 ◽  
Vol 63 (7) ◽  
pp. 872-878 ◽  
Author(s):  
M. W. Oliver ◽  
J. J. Miller
Keyword(s):  
Pyramidal Neurons ◽  
Epileptiform Activity ◽  
Pyramidal Cells ◽  
Repetitive Stimulation ◽  
Membrane Properties ◽  
Stratum Radiatum ◽  
Inhibitory Processes ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Ca1 ◽  
Stimulation Of

To determine the alterations in cellular function which may contribute to the chronic predisposition of neuronal tissue to epileptiform activity, the membrane properties and inhibitory processes of hippocampal CA1 pyramidal cells were investigated using in vitro slices prepared from commissural-kindled rats. No changes were observed in resting membrane potential, input resistance, spike amplitude, and membrane time constant of "kindled" CA1 pyramidal neurons when compared with controls. There were also no differences between control and kindled preparations in the amplitude of recurrent inhibitory postsynaptic potentials (IPSP) and in the duration of inhibition produced by either alvear (Alv) or stratum radiatum (SR) stimulation. Irrespective of group, repetitive stimulation of the Alv reduced the amplitude of the recurrent IPSP but failed to induce seizurelike activity. On the other hand, repetitive stimulation of SR frequently produced a neuronal burst discharge even though the duration and to some extent the amplitude of orthodromic inhibition was increased. On the basis of these data, it may be suggested that chronic changes in CA1 pyramidal cell membrane properties and transient reductions of inhibitory processes do not underlie the enhanced sensitivity of these neurons to seizure activity associated with kindling.

Group I mGluRs Increase Excitability of Hippocampal CA1 Pyramidal Neurons by a PLC-Independent Mechanism

2002 ◽  
Vol 88 (1) ◽  
pp. 107-116 ◽  
Author(s):  
David R. Ireland ◽  
Wickliffe C. Abraham
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Receptor Subtypes ◽  
Ca1 Pyramidal Neurons ◽  
Group I ◽  
Hippocampal Ca1 ◽  
Group I Mglurs ◽  
Induced Changes

Previous studies have implicated phospholipase C (PLC)-linked Group I metabotropic glutamate receptors (mGluRs) in regulating the excitability of hippocampal CA1 pyramidal neurons. We used intracellular recordings from rat hippocampal slices and specific antagonists to examine in more detail the mGluR receptor subtypes and signal transduction mechanisms underlying this effect. Application of the Group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) suppressed slow- and medium-duration afterhyperpolarizations (s- and mAHP) and caused a consequent increase in cell excitability as well as a depolarization of the membrane and an increase in input resistance. Interestingly, with the exception of the suppression of the mAHP, these effects were persistent, and in the case of the sAHP lasting for more than 1 h of drug washout. Preincubation with the specific mGluR5 antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), reduced but did not completely prevent the effects of DHPG. However, preincubation with both MPEP and the mGluR1 antagonist LY367385 completely prevented the DHPG-induced changes. These results demonstrate that the DHPG-induced changes are mediated partly by mGluR5 and partly by mGluR1. Because Group I mGluRs are linked to PLC via G-protein activation, we also investigated pathways downstream of PLC activation, using chelerythrine and cyclopiazonic acid to block protein kinase C (PKC) and inositol 1,4,5-trisphosphate-(IP3)-activated Ca2+ stores, respectively. Neither inhibitor affected the DHPG-induced suppression of the sAHP or the increase in excitability nor did an inhibitor of PLC itself, U-73122. Taken together, these results argue that in CA1 pyramidal cells in the adult rat, DHPG activates mGluRs of both the mGluR5 and mGluR1 subtypes, causing a long-lasting suppression of the sAHP and a consequent persistent increase in excitability via a PLC-, PKC-, and IP3-independent transduction pathway.

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.

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.

Cumulative Effects of Glutamate Microstimulation on Ca2+ Responses of CA1 Hippocampal Pyramidal Neurons in Slice

2000 ◽  
Vol 83 (1) ◽  
pp. 90-98 ◽  
Author(s):  
John A. Connor ◽  
Robert J. Cormier
Keyword(s):  
Time Course ◽  
Pyramidal Neurons ◽  
Stratum Radiatum ◽  
Neuron Death ◽  
Hippocampal Pyramidal Neurons ◽  
Ca1 Neurons ◽  
Hippocampal Ca1 ◽  
High Resolution Images ◽  
Stimulation Of

Glutamate stimulation of hippocampal CA1 neurons in slice was delivered via iontophoresis from a microelectrode. Five pulses (∼5 μA, 10 s duration, repeated at 1 min intervals) were applied with the electrode tip positioned in the stratum radiatum near the dendrites of a neuron filled with the Ca2+ indicator fura-2. A single stimulus set produced Ca2+ elevations that ranged from several hundred nM to several μM and that, in all but a few neurons, recovered within 1 min of stimulus termination. Subsequent identical stimulation produced Ca2+ elevations that outlasted the local glutamate elevations by several minutes as judged by response recoveries in neighboring cells or in other parts of the same neuron. These long responses ultimately recovered but persisted for up to 10 min and were most prominent in the mid and distal dendrites. Recovery was not observed for responses that spread to the soma. The elevated Ca2+ levels were accompanied by membrane depolarization but did not appear to depend on the depolarization. High-resolution images demonstrated responsive areas that involved only a few μm of dendrite. Our results confirm the previous general findings from isolated and cell culture neurons that glutamate stimulation, if carried beyond a certain range, results in long-lasting Ca2+ elevation. The response characterized here in mature in situ neurons was significantly different in terms of time course and reversibility. We suggest that the extended Ca2+ elevations might serve not only as a trigger for delayed neuron death but, where more spatially restricted, as a signal for local remodeling in dendrites.

scholarly journals Neuronal primary cilia regulate pyramidal cell positioning to the deep and superficial sublayers in the hippocampal CA1

2021 ◽  
Author(s):  
Juan Yang ◽  
Liyan Qiu ◽  
Xuanmao Chen
Keyword(s):  
Pyramidal Cell ◽  
Cortical Neurons ◽  
Primary Cilia ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Stratum Radiatum ◽  
Neuronal Cilia ◽  
Hippocampal Ca1 ◽  
Cortical Pyramidal Neurons ◽  
Cell Positioning

It is well-recognized that primary cilia regulate embryonic neurodevelopment, but little is known about their roles in postnatal neurodevelopment. The striatum pyramidal (SP) of hippocampal CA1 consists of superficial and deep sublayers, however, it is not well understood how early- and late-born pyramidal neurons position to two sublayers postnatally. Here we show that neuronal primary cilia emerge after CA1 pyramidal cells have reached SP, but before final neuronal positioning. The axonemes of primary cilia of early-born neurons point to the stratum oriens (SO), whereas late-born neuronal cilia orient toward the stratum radiatum (SR), reflecting an inside-out lamination pattern. Neuronal primary cilia in SP undergo marked changes in morphology and orientation from postnatal day 5 (P5) to P14, concurrent with pyramidal cell positioning to the deep and superficial sublayers and with neuronal maturation. Transgenic overexpression of Arl13B, a protein regulating ciliogenesis, not only elongates primary cilia and promotes earlier cilia protrusion, but also affects centriole positioning and cilia orientation in SP. The centrioles of late-born neurons migrate excessively to cluster at SP bottom before primary cilia protrusion and a reverse movement back to the main SP. Similarly, this pull-back movement of centriole/cilia is also identified on late-born cortical pyramidal neurons, although early- and late-born cortical neurons display the same cilia orientation. Together, this study provides the first evidence demonstrating that late-born pyramidal neurons exhibit a reverse movement for cell positioning, and primary cilia regulate pyramidal neuronal positioning to the deep and superficial sublayers in the hippocampus.

Posttetanic Excitation Mediated by GABAA Receptors in Rat CA1 Pyramidal Neurons

1997 ◽  
Vol 77 (4) ◽  
pp. 2213-2218 ◽  
Author(s):  
Tomi Taira ◽  
Karri Lamsa ◽  
Kai Kaila
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Long Term Potentiation ◽  
Neuronal Firing ◽  
Stratum Radiatum ◽  
Tetanic Stimulation ◽  
Glutamate Antagonists ◽  
Ca1 Pyramidal Neurons ◽  
Spike Firing

Taira, Tomi, Karri Lamsa, and Kai Kaila. Posttetanic excitation mediated by GABAA receptors in rat CA1 pyramidal neurons. J.Neurophysiol. 77: 2213–2218, 1997. The contributions of γ-aminobutyric acid (GABA) receptors to posttetanic excitation of CA1 pyramidal neurons in rat hippocampal slices were studied using extracellular and intracellular recording techniques. Synaptic responses were evoked on tetanic stimulation (100–200 Hz, 40–100 pulses) applied in stratum radiatum close (300–600 μm) to the recording site. Under control conditions, tetanic stimulation resulted in a triphasic depolarization/hyperpolarization/sustained depolarization sequence in area CA1 pyramidal cells. The late depolarization usually gave rise to a prolonged (≤3 s) spike firing. The late depolarization and the associated spike firing were blocked both specifically and completely (within a time window of 3–6 min starting from picrotoxin application) by the GABAA receptor antagonist picrotoxin (PiTX, 100 μM). Paradoxically, at this early stage of PiTX application, overall neuronal firing was attenuated to a higher degree than what was achieved by ionotropic glutamate antagonists. Complete block of ionotropic glutamate receptors by the antagonists d-2-amino-5-phosphonopentoate (AP5, 80 μM), 6-nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-dione (NBQX, 10 μM), and ketamine (50 μM) blocked the initial fast depolarization and suppressed the late one. Exposure to a permeable inhibitor of carbonic anhydrase, ethoxyzolamide (EZA, 50 μM) inhibited the late, apparently GABA-mediated depolarization. It is concluded that GABA can provide the main posttetanic excitatory drive in the adult hippocampus. The present results suggest that intense activation of GABAergic interneurons may accentuate the excitation of principal neurons and, hence, play an important facilitatory role in the induction of long-term potentiation (LTP) and epileptogenesis.

IPSPs modulate spike backpropagation and associated [Ca2+]i changes in the dendrites of hippocampal CA1 pyramidal neurons

1996 ◽  
Vol 76 (5) ◽  
pp. 2896-2906 ◽  
Author(s):  
H. Tsubokawa ◽  
W. N. Ross
Keyword(s):  
Action Potentials ◽  
Pyramidal Neurons ◽  
Time Window ◽  
Proximal Part ◽  
Stratum Radiatum ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Ca1 ◽  
Dendritic Branches ◽  
Apical Dendrites ◽  
Stratum Lacunosum Moleculare

1. We studied the effects of synaptic inhibition on backpropagating Na+ spikes in the apical dendrites of CA1 pyramidal neurons in transverse slices from the rat hippocampus. Action potentials were evoked synaptically by stimulation in the stratum radiatum or antidromically by stimulation in the alveus. 2. Inhibitory postsynaptic potentials, evoked by stimulation in the stratum lacunosum moleculare, reduced the amplitude of single spikes in the distal dendrites but did not change the amplitudes in the somatic or proximal regions. Inhibition also reduced the spike-associated [Ca2+]i changes in the distal dendrites but had little effect on the changes in the proximal part of the cell. Both of these results are consistent with inhibition converting actively backpropagating spikes into passively spreading potentials at some point in the arbor. 3. In most cells, the spike amplitude reduction in the distal dendrites was blocked by bicuculline methiodide (10 microM) and inhibition was most effective when evoked in a time window < 10 ms preceding the action potential. This suggests that the amplitude reduction was due to a conductance shunt activated by gamma-aminobuturic acid-A (GABAA) receptors. Synaptically evoked GABAB responses were detected but usually did not block spike propagation. 4. Direct hyperpolarization in the distal dendrites was also effective in blocking antidromically evoked spike backpropagation but probably does not contribute when the action potentials are evoked synaptically. 5. This effect of inhibition is different from its usual function in synaptic integration because spike generation and propagation down the axon are not significantly affected. This kind of inhibition might be important in regulating transient [Ca2+]i changes in the dendrites including individual dendritic branches.

Distribution of Slow AHP Channels on Hippocampal CA1 Pyramidal Neurons

2000 ◽  
Vol 83 (3) ◽  
pp. 1756-1759 ◽  
Author(s):  
John M. Bekkers
Keyword(s):  
Action Potentials ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Apical Dendrite ◽  
Ca1 Pyramidal Cells ◽  
Ca1 Pyramidal Neurons ◽  
Basal Dendrites ◽  
Hippocampal Ca1 ◽  
Cell Current ◽  
Whole Cell Current

This work was designed to localize the Ca2+-activated K+ channels underlying the slow afterhyperpolarization (sAHP) in hippocampal CA1 pyramidal cells. Cell-attached patches on the proximal 100 μm of the apical dendrite contained K+ channels, but not sAHP channels, activated by backpropagating action potentials. Amputation of the apical dendrite ∼30 μm from the soma, while simultaneously recording the sAHP whole cell current at the soma, depressed the sAHP amplitude by only ∼30% compared with control. Somatic cell-attached and nucleated patches did not contain sAHP current. Amputation of the axon ≥20 μm from the soma had little effect on the amplitude of the sAHP recorded in cortical pyramidal cells. By this process of elimination, it is suggested that sAHP channels may be concentrated in the basal dendrites of CA1 pyramids.

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