scholarly journals Barium Plateau Potentials of CA1 Pyramidal Neurons Elicit All-or-None Extracellular Alkaline Shifts Via the Plasma Membrane Calcium ATPase

2010 ◽  
Vol 104 (3) ◽  
pp. 1438-1444 ◽  
Author(s):  
Sachin Makani ◽  
Mitchell Chesler
Keyword(s):  
Plasma Membrane ◽  
High Speed ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Brain Regions ◽  
Low Noise ◽  
Body Region ◽  
Pipette Solution ◽  
Ca1 Pyramidal Neurons ◽  
Ca1 Region

In many brain regions, synchronous neural activity causes a rapid rise in extracellular pH. In the CA1 region of hippocampus, this population alkaline transient (PAT) enhances responses from postsynaptic, pH-sensitive N-methyl-d-aspartate (NMDA) receptors. Recently, we showed that the plasma membrane Ca2+-ATPase (PMCA), a ubiquitous transporter that exchanges internal Ca2+ for external H+, is largely responsible for the PAT. It has also been shown that a PAT can be generated after replacing extracellular Ca2+ with Ba2+. The cause of this PAT is unknown, however, because the ability of the mammalian PMCA to transport Ba2+ is unclear. If the PMCA did not carry Ba2+, a different alkalinizing source would have to be postulated. Here, we address this issue in mouse hippocampal slices, using concentric (high-speed, low-noise) pH microelectrodes. In Ba2+-containing, Ca2+-free artificial cerebrospinal fluid, a single antidromic shock to the alveus elicited a large (0.1–0.2 unit pH), “all-or-none” PAT in the CA1 cell body region. In whole cell current clamp of single CA1 pyramidal neurons, the same stimulus evoked a prolonged plateau potential that was similarly all-or-none. Using this plateau as the voltage command in other cells, we recorded Ba2+-dependent surface alkaline transients (SATs). The SATs were suppressed by adding 5 mM extracellular HEPES and abolished when carboxyeosin (a PMCA inhibitor) was in the patch pipette solution. These results suggest that the PAT evoked in the presence of Ba2+ is caused by the PMCA and that this transporter is responsible for the PAT whether Ca2+ or Ba2+ is the charge carrying divalent cation.

scholarly journals Rapid Rise of Extracellular pH Evoked by Neural Activity Is Generated by the Plasma Membrane Calcium ATPase

2010 ◽  
Vol 103 (2) ◽  
pp. 667-676 ◽  
Author(s):  
Sachin Makani ◽  
Mitchell Chesler
Keyword(s):  
Plasma Membrane ◽  
High Speed ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Neuronal Population ◽  
Low Noise ◽  
Antidromic Activation ◽  
Ca1 Pyramidal Neurons ◽  
Alkaline Shift ◽  
Synchronous Firing

In hippocampus, synchronous activation of CA1 pyramidal neurons causes a rapid, extracellular, population alkaline transient (PAT). It has been suggested that the plasma membrane Ca2+-ATPase (PMCA) is the source of this alkalinization, because it exchanges cytosolic Ca2+ for external H+. Evidence supporting this hypothesis, however, has thus far been inconclusive. We addressed this long-standing problem by measuring surface alkaline transients (SATs) from voltage-clamped CA1 pyramidal neurons in juvenile mouse hippocampal slices, using concentric (high-speed, low-noise) pH microelectrodes placed against the somata. In saline containing benzolamide (a poorly permeant carbonic anhydrase blocker), a 2-s step from −60 to 0 mV caused a mean SAT of 0.02 unit pH. Addition of 5 mM HEPES to the artificial cerebrospinal fluid diminished the SAT by 91%. Nifedipine reduced the SAT by 53%. Removal of Ca2+ from the saline abolished the SAT, and addition of BAPTA to the patch pipette reduced it by 79%. The inclusion of carboxyeosin (a PMCA inhibitor) in the pipette abolished the SAT, whether it was induced by a depolarizing step, or by simulated, repetitive, antidromic firing. The peak amplitude of the “antidromic” SAT of a single cell averaged 11% of the PAT elicited by comparable real antidromic activation of the CA1 neuronal population. Caloxin 2A1, an extracellular PMCA peptide inhibitor, blocked both the SAT and PAT by 42%. These results provide the first direct evidence that the PMCA can explain the extracellular alkaline shift elicited by synchronous firing.

scholarly journals Estradiol Increases Spine Density and NMDA-Dependent Ca2+ Transients in Spines of CA1 Pyramidal Neurons From Hippocampal Slices

1999 ◽  
Vol 81 (3) ◽  
pp. 1404-1411 ◽  
Author(s):  
Lucas D. Pozzo-Miller ◽  
Takafumi Inoue ◽  
Diane Dieuliis Murphy
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Input Resistance ◽  
Spine Density ◽  
Afferent Stimulation ◽  
Α Subunit ◽  
Ca1 Neurons ◽  
Ca1 Pyramidal Neurons ◽  
Ca1 Region

Estradiol increases spine density and NMDA-dependent Ca2+transients in spines of CA1 pyramidal neurons from hippocampal slices. To investigate the physiological consequences of the increase in spine density induced by estradiol in pyramidal neurons of the hippocampus, we performed simultaneous whole cell recordings and Ca2+ imaging in CA1 neuron spines and dendrites in hippocampal slices. Four- to eight-days in vitro slice cultures were exposed to 17β-estradiol (EST) for an additional 4- to 8-day period, and spine density was assessed by confocal microscopy of DiI-labeled CA1 pyramidal neurons. Spine density was doubled in both apical and basal dendrites of the CA1 region in EST-treated slices; consistently, a reduction in cell input resistance was observed in EST-treated CA1 neurons. Double immunofluorescence staining of presynaptic (synaptophysin) and postsynaptic (α-subunit of CaMKII) proteins showed an increase in synaptic density after EST treatment. The slopes of the input/output curves of both α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) postsynaptic currents were steeper in EST-treated CA1 neurons, consistent with the observed increase in synapse density. To characterize NMDA-dependent synaptic currents and dendritic Ca2+ transients during Schaffer collaterals stimulation, neurons were maintained at +40 mV in the presence of nimodipine, picrotoxin, and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). No differences in resting spine or dendritic Ca2+ levels were observed between control and EST-treated CA1 neurons. Intracellular Ca2+transients during afferent stimulation exhibited a faster slope and reached higher levels in spines than in adjacent dendrites. Peak Ca2+ levels were larger in both spines and dendrites of EST-treated CA1 neurons. Ca2+ gradients between spine heads and dendrites during afferent stimulation were also larger in EST-treated neurons. Both spine and dendritic Ca2+transients during afferent stimulation were reversibly blocked byd,l-2-amino-5-phosphonovaleric acid (d,l-APV). The increase in spine density and the enhanced NMDA-dependent Ca2+ signals in spines and dendrites induced by EST may underlie a threshold reduction for induction of NMDA-dependent synaptic plasticity in the hippocampus.

scholarly journals Increased Calbindin D28k Expression via Long-Term Alternate-Day Fasting Does Not Protect against Ischemia-Reperfusion Injury: A Focus on Delayed Neuronal Death, Gliosis and Immunoglobulin G Leakage

2021 ◽  
Vol 22 (2) ◽  
pp. 644
Author(s):  
Hyejin Sim ◽  
Tae-Kyeong Lee ◽  
Yeon Ho Yoo ◽  
Ji Hyeon Ahn ◽  
Dae Won Kim ◽  
...  
Keyword(s):  
Immunoglobulin G ◽  
Pyramidal Neurons ◽  
Short Term Memory ◽  
Forebrain Ischemia ◽  
Short Term ◽  
Term Memory ◽  
Transient Forebrain Ischemia ◽  
Ca1 Pyramidal Neurons ◽  
Ca1 Region ◽  
Calbindin D28k

Calbindin-D28k (CB), a calcium-binding protein, mediates diverse neuronal functions. In this study, adult gerbils were fed a normal diet (ND) or exposed to intermittent fasting (IF) for three months, and were randomly assigned to sham or ischemia operated groups. Ischemic injury was induced by transient forebrain ischemia for 5 min. Short-term memory was examined via passive avoidance test. CB expression was investigated in the Cornu Ammonis 1 (CA1) region of the hippocampus via western blot analysis and immunohistochemistry. Finally, histological analysis was used to assess neuroprotection and gliosis (microgliosis and astrogliosis) in the CA1 region. Short-term memory did not vary significantly between ischemic gerbils with IF and those exposed to ND. CB expression was increased significantly in the CA1 pyramidal neurons of ischemic gerbils with IF compared with that of gerbils fed ND. However, the CB expression was significantly decreased in ischemic gerbils with IF, similarly to that of ischemic gerbils exposed to ND. The CA1 pyramidal neurons were not protected from ischemic injury in both groups, and gliosis (astrogliosis and microgliosis) was gradually increased with time after ischemia. In addition, immunoglobulin G was leaked into the CA1 parenchyma from blood vessels and gradually increased with time after ischemic insult in both groups. Taken together, our study suggests that IF for three months increases CB expression in hippocampal CA1 pyramidal neurons; however, the CA1 pyramidal neurons are not protected from transient forebrain ischemia. This failure in neuroprotection may be attributed to disruption of the blood–brain barrier, which triggers gliosis after ischemic insults.

Modulation of the Ca2+-Activated K+ Current sI AHP by aPhosphatase-Kinase Balance Under Basal Conditions inRat CA1 Pyramidal Neurons

1998 ◽  
Vol 79 (6) ◽  
pp. 3252-3256 ◽  
Author(s):  
Paola Pedarzani ◽  
Michael Krause ◽  
Trude Haug ◽  
Johan F. Storm ◽  
Walter Stühmer
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Phosphodiesterase Inhibitors ◽  
Gradual Decrease ◽  
Patch Clamp Technique ◽  
Hippocampal Pyramidal Neurons ◽  
Ca1 Pyramidal Neurons ◽  
Type Iv ◽  
Whole Cell Patch Clamp ◽  
Firing Properties

Pedarzani, Paola, Michael Krause, Trude Haug, Johan F. Storm, and Walter Stühmer. Modulation of the Ca2+-activated K+ current s I AHP by a phosphatase-kinase balance under basal conditions in rat CA1 pyramidal neurons. J. Neurophysiol. 79: 3252–3256, 1998. The slow Ca2+-activated K+ current, s I AHP, underlying spike frequency adaptation, was recorded with the whole cell patch-clamp technique in CA1 pyramidal neurons in rat hippocampal slices. Inhibitors of serine/threonine protein phosphatases (microcystin, calyculin A, cantharidic acid) caused a gradual decrease of s I AHP amplitude, suggesting the presence of a basal phosphorylation-dephosphorylation turnover regulating s I AHP. Because selective calcineurin (PP-2B) inhibitors did not affect the amplitude of s I AHP, protein phosphatase 1 (PP-1) or 2A (PP-2A) are most likely involved in the basal regulation of this current. The ATP analogue, ATP-γ-S, caused a gradual decrease in the s I AHP amplitude, supporting a role of protein phosphorylation in the basal modulation of s I AHP. When the protein kinase A (PKA) inhibitor adenosine-3′,5′-monophosphorothioate, Rp-isomer (Rp-cAMPS) was coapplied with the phosphatase inhibitor microcystin, it prevented the decrease in the s I AHP amplitude that was observed when microcystin alone was applied. Furthermore, inhibition of PKA by Rp-cAMPS led to an increase in the s I AHP amplitude. Finally, an adenylyl cyclase inhibitor (SQ22,536) and adenosine 3′,5′-cyclic monophosphate-specific type IV phosphodiesterase inhibitors (Ro 20–1724 and rolipram) led to an increase or a decrease in the s I AHP amplitude, respectively. These findings suggest that a balance between basally active PKA and a phosphatase (PP-1 or PP-2A) is responsible for the tonic modulation of s I AHP, resulting in a continuous modulation of excitability and firing properties of hippocampal pyramidal neurons.

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.

scholarly journals Optogenetic activation of SST-positive interneurons restores hippocampal theta oscillation impairment induced by soluble amyloid beta oligomersin vivo

2018 ◽  
Author(s):  
Hyowon Chung ◽  
Kyerl Park ◽  
Hyun Jae Jang ◽  
Michael M Kohl ◽  
Jeehyun Kwag
Keyword(s):  
Learning And Memory ◽  
Peak Power ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Theta Oscillations ◽  
Ca1 Pyramidal Neurons ◽  
Theta Frequency ◽  
Hippocampal Theta

AbstractAbnormal accumulation of amyloid β oligomers (AβO) is a hallmark of Alzheimer’s disease (AD), which leads to learning and memory deficits. Hippocampal theta oscillations that are critical in spatial navigation, learning and memory are impaired in AD. Since GABAergic interneurons, such as somatostatin-positive (SST+) and parvalbumin-positive (PV+) interneurons, are believed to play key roles in the hippocampal oscillogenesis, we asked whether AβO selectively impairs these SST+ and PV+ interneurons. To selectively manipulate SST+ or PV+ interneuron activity in mice with AβO pathologyin vivo, we co-injected AβO and adeno-associated virus (AAV) for expressing floxed channelrhodopsin-2 (ChR2) into the hippocampus of SST-Cre or PV-Cre mice. Local field potential (LFP) recordingsin vivoin these AβO–injected mice showed a reduction in the peak power of theta oscillations and desynchronization of spikes from CA1 pyramidal neurons relative to theta oscillations compared to those in control mice. Optogenetic-activation of SST+ but not PV+ interneurons in AβO–injected mice fully restored the peak power of theta oscillations and resynchronized the theta spike phases to a level observed in control mice.In vitrowhole-cell voltage-clamp recordings in CA1 pyramidal neurons in hippocampal slices treated with AβO revealed that short-term plasticity of SST+ interneuron inhibitory inputs to CA1 pyramidal neurons at theta frequency were selectively disrupted while that of PV+ interneuron inputs were unaffected. Together, our results suggest that dysfunction in inputs from SST+ interneurons to CA1 pyramidal neurons may underlie the impairment of theta oscillations observed in AβO-injected micein vivo.Our findings identify SST+ interneurons as a target for restoring theta-frequency oscillations in early AD.

scholarly journals Streptozotocin Inhibits Electrophysiological Determinants of Excitatory and Inhibitory Synaptic Transmission in CA1 Pyramidal Neurons of Rat Hippocampal Slices: Reduction of These Effects by Edaravone

2016 ◽  
Vol 40 (6) ◽  
pp. 1274-1288 ◽  
Author(s):  
Ting Ju ◽  
Yuru Li ◽  
Xiaoran Wang ◽  
Lifeng Xiao ◽  
Li Jiang ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Paired Pulse ◽  
Ca1 Pyramidal Neurons ◽  
Postsynaptic Currents ◽  
Pulse Ratio ◽  
Synaptic Mechanisms

Background: Streptozotocin (STZ) has served as an agent to generate an Alzheimer's disease (AD) model in rats, while edaravone (EDA), a novel free radical scavenger, has recently emerged as an effective treatment for use in vivo and vitro AD models. However, to date, these beneficial effects of EDA have only been clearly demonstrated within STZ-induced animal models of AD and in cell models of AD. A better understanding of the mechanisms of EDA may provide the opportunity for their clinical application in the treatment of AD. Therefore, the purpose of this study was to investigate the underlying mechanisms of STZ and EDA as assessed upon electrophysiological alterations in CA1 pyramidal neurons of rat hippocampal slices. Methods: Through measures of evoked excitatory postsynaptic currents (eEPSCs), AMPAR-mediated eEPSCs (eEPSCsAMPA), evoked inhibitory postsynaptic currents (eIPSCs), evoked excitatory postsynaptic current paired pulse ratio (eEPSC PPR) and evoked inhibitory postsynaptic current paired pulse ratio (eIPSC PPR), it was possible to investigate mechanisms as related to the neurotoxicity of STZ and reductions in these effects by EDA. Results: Our results showed that STZ (1000 µM) significantly inhibited peak amplitudes of eEPSCs, eEPSCsAMPA and eIPSCs, while EDA (1000 µM) attenuated these STZ-induced changes at holding potentials ranging from -60mV to +40 mV for EPSCs and -60mV to +20 mV for IPSCs. Our work also indicated that mean eEPSC PPR were substantially altered by STZ, effects which were partially restored by EDA. In contrast, no significant effects upon eIPSC PPR were obtained in response to STZ and EDA. Conclusion: Our data suggest that STZ inhibits glutamatergic transmission involving pre-synaptic mechanisms and AMPAR, and that STZ inhibits GABAergic transmission by post-synaptic mechanisms within CA1 pyramidal neurons. These effects are attenuated by EDA.

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.

scholarly journals Progesterone Withdrawal Reduces Paired-Pulse Inhibition in Rat Hippocampus: Dependence on GABAA Receptor α4 Subunit Upregulation

2003 ◽  
Vol 89 (1) ◽  
pp. 186-198 ◽  
Author(s):  
Fu-Chun Hsu ◽  
Sheryl S. Smith
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Extracellular Recording ◽  
Pyramidal Cells ◽  
Chronic Administration ◽  
Female Rats ◽  
Stratum Radiatum ◽  
Intraventricular Administration ◽  
Paired Pulse ◽  
Ca1 Region

Withdrawal from the endogenous steroid progesterone (P) after chronic administration increases anxiety and seizure susceptibility via declining levels of its potent GABA-modulatory metabolite 3α-OH-5α-pregnan-20-one (3α,5αTHP). This 3α,5α-THP withdrawal also results in a decreased decay time constant for GABA-gated current assessed using whole cell patch-clamp techniques on pyramidal cells acutely dissociated from CA1 hippocampus. The purpose of this study was to test the hypothesis that the decreases in total integrated GABA-gated current observed at the level of the isolated pyramidal cell would be manifested as a reduced GABA inhibition at the circuit level following hormone withdrawal. Toward this end, adult, female rats were administered P via subcutaneous capsule for 3 wk using a multiple withdrawal paradigm. We then evaluated paired-pulse inhibition (PPI) of pyramidal neurons in CA1 hippocampus using extracellular recording techniques in hippocampal slices from rats 24 h after removal of the capsule (P withdrawal, P Wd). The population spike (PS) was recorded at the stratum pyramidale following homosynaptic orthodromic stimulation in the nearby stratum radiatum. The threshold for eliciting a response was decreased after P Wd, and the mean PS amplitude was significantly increased compared with control values at this time. Paired pulses with 10-ms inter-pulse intervals were then applied across an intensity range from 2 to 20 times threshold. Evaluation of paired-pulse responses showed a significant 40–50% reduction in PPI for PS recorded in the hippocampal CA1 region after P Wd, suggesting an increase in circuit excitability. At this time, enhancement of PPI by the benzodiazepine lorazepam (LZM; 10 μM) was prevented, while pentobarbital (10 μM) potentiation of PPI was comparable to control levels of response. These data are consistent with upregulation of the α4 subunit of the GABAA receptor (GABAR) as we have previously shown. Moreover, the reduced PPI caused by P Wd was prevented by suppression of GABAR α4-subunit expression following intraventricular administration of specific antisense oligonucleotides (1 μg/h for 72 h). These results demonstrating a reduction in PPI following P Wd suggest that GABAergic-mediated recurrent or feed-forward inhibition occurring at the circuit level were decreased following P Wd in female rats, an effect at least partially attributable to alterations in the GABAR subunit gene expression.

Astrocytic Glutamate Release-Induced Transient Depolarization and Epileptiform Discharges in Hippocampal CA1 Pyramidal Neurons

2005 ◽  
Vol 94 (6) ◽  
pp. 4121-4130 ◽  
Author(s):  
Ning Kang ◽  
Jun Xu ◽  
Qiwu Xu ◽  
Maiken Nedergaard ◽  
Jian Kang
Keyword(s):  
Laser Scanning ◽  
Pyramidal Neurons ◽  
Glutamate Release ◽  
Hippocampal Slices ◽  
Epileptic Seizures ◽  
Epileptic Activity ◽  
Laser Scanning Microscopy ◽  
Patch Clamp Recording ◽  
Ca1 Pyramidal Neurons ◽  
Epileptiform Discharges

A paroxysmal depolarization shift (PDS) has been suggested to be a hallmark for epileptic activity in partial-onset seizures. By monitoring membrane potentials and currents in pairs of pyramidal neurons and astrocytes with dual patch-clamp recording and exocytosis of vesicles from astrocytes with two-photon laser scanning microscopy in hippocampal slices, we found that infusion of inositol 1,4,5-trisphosphate (IP3) into astrocytes by patch pipettes induced astrocytic glutamate release that triggered a transient depolarization (TD) and epileptiform discharges in CA1 pyramidal neurons. The TD is due to a tetrodotoxin (TTX)-insensitive slowly decaying transient inward current (STC). Astrocytic glutamate release simultaneously triggers both the STC in pyramidal neurons and a transport current (TC) in astrocytes. The neuronal STC is mediated by ionotropic glutamate receptors leading to the TD and epileptiform discharges; while the astrocytic TC is a glutamate reuptake current resulting from transporting released glutamate into the patched astrocyte. Fusion of a large vesicle in astrocytes was immediately followed by an astrocytic TC, suggesting that the fused vesicle contains glutamate. Both fusion of large vesicles and astrocytic TCs were blocked by tetanus toxin (TeNT), suggesting that astrocytic glutamate release is via SNARE-dependent exocytosis of glutamate-containing vesicles. In the presence of TTX, the epileptogenic reagent, 4-AP, also induced similar neuronal STCs and astrocytic TCs, suggesting that astrocytic glutamate release may play an epileptogenic role in initiation of epileptic seizures under pathological conditions. Our study provides a novel mechanism, astrocytic release of glutamate, for seizure initiation.

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