Rat Hippocampal CA1 Pyramidal Neurons Research Articles

Selective Shunting of the NMDA EPSP Component by the Slow Afterhyperpolarization in Rat CA1 Pyramidal Neurons

Pyramidal neuron dendrites express voltage-gated conductances that control synaptic integration and plasticity, but the contribution of the Ca(2+)-activated K(+)-mediated currents to dendritic function is not well understood. Using dendritic and somatic recordings in rat hippocampal CA1 pyramidal neurons in vitro, we analyzed the changes induced by the slow Ca(2+)-activated K(+)-mediated afterhyperpolarization (sAHP) generated by bursts of action potentials on excitatory postsynaptic potentials (EPSPs) evoked at the apical dendrites by perforant path-Schaffer collateral stimulation. Both the amplitude and decay time constants of EPSPs (tau(EPSP)) were reduced by the sAHP in somatic recordings. In contrast, the dendritic EPSP amplitude remained unchanged, whereas tau(EPSP) was reduced. Temporal summation was reduced and spatial summation linearized by the sAHP. The amplitude of the isolated N-methyl-D-aspartate component of EPSPs (EPSP(NMDA)) was reduced, whereas tau(NMDA) was unaffected by the sAHP. In contrast, the sAHP did not modify the amplitude of the isolated EPSP(AMPA) but reduced tau(AMPA) both in dendritic and somatic recordings. These changes are attributable to a conductance increase that acted mainly via a selective "shunt" of EPSP(NMDA) because they were absent under voltage clamp, not present with imposed hyperpolarization simulating the sAHP, missing when the sAHP was inhibited with isoproterenol, and reduced under block of EPSP(NMDA). EPSPs generated at the basal dendrites were similarly modified by the sAHP, suggesting both a somatic and apical dendritic location of the sAHP channels. Therefore the sAHP may play a decisive role in the dendrites by regulating synaptic efficacy and temporal and spatial summation.

Retrograde modulation of presynaptic release probability through signaling mediated by PSD-95–neuroligin

The structure and function of presynaptic and postsynaptic components of the synapse are highly coordinated. How such coordination is achieved and the molecules involved in this process have not been clarified. Several lines of evidence suggest that presynaptic functionalities are regulated by retrograde mechanisms from the postsynaptic side. We therefore sought postsynaptic mechanisms responsible for trans-synaptic regulation of presynaptic function at excitatory synapses in rat hippocampal CA1 pyramidal neurons. We show here that the postsynaptic complex of scaffolding protein PSD-95 and neuroligin can modulate the release probability of transmitter vesicles at synapse in a retrograde way, resulting in altered presynaptic short-term plasticity. Presynaptic beta-neurexin serves as a likely presynaptic mediator of this effect. Our results indicate that trans-synaptic protein-protein interactions can link postsynaptic and presynaptic function.

Research on characteristics of neuron potassium channel under low level laser irradiation

Acutely isolated rat hippocampal CA3 pyramidal neurons were irradiated with a semiconductor laser of wavelength 670 nm and power 5 mW. The properties of transient outward potassium (K+) channel were investigated using the whole-cell patch clamp technique. The experiment revealed that low level laser reduced the amplitudes of IA in a voltage-dependent and reversible manner. The steady-state activation and inactivation processes of IA were significantly affected by laser irradiation. And the steady-state activation curve shifted towards positive potential direction, altering the slope factor of curve and increasing the half-activation voltage. However, the steady-state inactivation curve shifted towards negative potential direction, reducing the half-inactivation voltage without changing the slope factor. The results show that low level laser irradiation could change the characteristics of transient outward K+ channel. Accordingly, the firing of action potential and the physiological function of neurons were adjusted as a result of low level laser irradiation, which might contribute to the recovery and regeneration of injured neurons.

Optical imaging of dendritic propagating potential in heterosynaptic associative LTP of rat hippocampal CA1 pyramidal neurons

Optical imaging of dendritic propagating potential in heterosynaptic associative LTP of rat hippocampal CA1 pyramidal neurons

Effects of tianeptine on changes of plasticity induced by chronic stress in the rat hippocampal CA3 pyramidal neuronal apical dendrites

目的 探讨抗抑郁剂噻奈普汀对慢性应激大鼠海马CA3区锥体细胞顶树突形态的效应.方法 将45只雄性Sprague-Dawley大鼠(2月龄),随机分为对照组、应激组及应激给药组,每组15只.高尔基(Golgi)镀染法测定海马CA3区锥体细胞顶树突分支及一级树突直径,常规透射电镜观察树突细胞骨架特别是微管的改变.结果 应激给药组大鼠海马CA3区锥体细胞顶树突分支数目[(15.37±1.54)支]较应激组的分支数目[(13.06±1.28)支]明显增多,与对照组[(16.29±1.95)支]差异无显著性;一级树突直径[(5.74±0.87)μm]较应激组[(6.41±0.94)μm]明显变小,与对照组(5.67±0.83)μm无明显差别;与应激组比较,应激给药组树突骨架基本完整.结论 噻奈普汀可抑制慢性应激导致的大鼠海马CA3区锥体细胞顶树突可塑性的改变。

BDNF occludes GABABreceptor-mediated inhibition of GABA release in rat hippocampal CA1 pyramidal neurons

During the development of the rat hippocampus, both gamma-aminobutyric acid (GABA)(B) autoreceptors and brain-derived neurotrophic factor (BDNF) play important roles in the formation of GABAergic synapses as well as in the GABA(A) receptor-mediated transmissions. While a number of studies have reported rapid effects of BDNF on GABA(A) receptor-mediated responses, the interactions between GABA(B) autoreceptors and BDNF are less clear. Using conventional whole-cell patch-clamp recordings, we demonstrated here that BDNF significantly occludes baclofen-induced suppression of GABA(A) receptor-mediated transmissions in each of the preparations including hippocampal slices prepared from P14 rats, hippocampal CA1 pyramidal neurons isolated from P14 and P21 rats, and cultured hippocampal pyramidal neurons. This effect of BDNF was rapid and reversible, and was mediated via the activation of presynaptic TrkB receptor tyrosine kinases, and subsequent activation of phospholipase C and protein kinase C. On the contrary, in hippocampal CA1 pyramidal neurons isolated from P7 rats, BDNF failed to occlude the GABA(B) receptor-mediated inhibition of GABA release. Thus, the ability of BDNF to occlude the GABA(B) receptor-mediated inhibition of GABA release develops between P7 and P14. This demonstrates a novel aspect of the effects of BDNF on inhibitory transmissions in rat hippocampus, which may have some functional roles in the induction of developmental plasticity and/or pathophysiology of epilepsy.

Veratridine‐Induced Wet Dog Shake Behaviour and Apoptosis in Rat Hippocampus

We have previously evaluated veratridine as an in vitro model of seizure using conventional electrophysiological recordings in rat hippocampal CA1 pyramidal neurones. The aim of this investigation is to further characterize this convulsant as an in vivo model of seizure. Veratridine was administered intraperitoneally to male Fisher rats in a dose range of 100-400 mug/kg. Within 5 min. after the injections, the animals entered a quiescent period which was followed 10-15 min. later by facial automatism (washing), grooming, masticatory jaw movement and profuse salivation. This phenomenon was followed by the development of wet dog shake and forelimb clonus. The time (mean+/-S.E.M.) for the onset of induction of these shakes for all tested doses was 31.65+/-2.85 min. and the number of shakes (mean+/-S.E.M.) 30 min. after the onset was 17.2+/-2.85. The onset and number of wet dog shakes induced by veratridine was dose-dependent. No rat death was recorded until 2 weeks after the experiments. Histopathological studies of animals 2 weeks after veratridine administration showed evidence of apoptosis in the hippocampus. Our results indicate that veratridine produced a behavioural pattern of a limbic seizure which mimics temporal lobe epilepsy in man. Based on our previous findings in vitro and of this investigation in vivo, veratridine can be used as an experimental tool to evaluate potential antiepileptic drugs effective against this type of limbic behaviour.

Background Activity Regulates Excitability of Rat Hippocampal CA1 Pyramidal Neurons by Adaptation of a K+ Conductance

In the in vivo brain background synaptic activity has a strong modulatory influence on neuronal excitability. Here we report that in rat hippocampal slices, blockade of endogenous in vitro background activity results in an increased excitability of CA1 pyramidal neurons within tens of minutes. The increase in excitability constitutes a leftward shift in the input-output relationship of pyramidal neurons, indicating a reduced threshold for the induction of action potentials. The increase in excitability results from an adaptive decrease in a sustained K+ conductance, as recorded from somatic cell-attached patches. After 20 min of blockade of background activity, the mean sustained K+ current amplitude in somatic patches was reduced to 46 +/- 9% of that in time-matched control patches. Blockade of background activity did not affect fast Na+ conductance. Together, these results suggests that the reduction in K+ conductance serves as an adaptive mechanism to increase the excitability of CA1 pyramidal neurons in response to changes in background activity such that the dynamic range of the input-output relationship is effectively maintained.

Induction and maintenance of late‐phase long‐term potentiation in isolated dendrites of rat hippocampal CA1 pyramidal neurones

Expression of N-methyl-d-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) in the CA1 region of the hippocampus can be divided into an early (1-2 h), protein synthesis-independent phase and a late (>4 h), protein synthesis-dependent phase. In this study we have addressed whether the de novo protein synthesis required for the expression of late-LTP can be sustained solely from the translation of mRNAs located in the dendrites of CA1 pyramidal neurones. Our results show that late-LTP, lasting at least 5 h, can be maintained in hippocampal slices where the dendrites located in stratum radiatum have been isolated from their cell bodies by a microsurgical cut. The magnitude of the potentiation of the slope of field EPSPs in these 'isolated' slices was similar to that recorded in 'intact' slices. Incubation of the slices with the mRNA translation inhibitor cycloheximide or the mammalian target of rapamycin (mTOR) inhibitor rapamycin blocked late-LTP in both 'intact' and 'isolated' slice preparations. In contrast, incubation of slices with the transcription inhibitor, actinomycin D, resulted in a reduction of sustained potentiation, at 4 h, in 'intact' slices while in 'isolated' slices the magnitude of potentiation was similar to that seen in untreated slices. These results indicate that late-LTP can be induced and maintained in 'isolated' dendritic preparations via translation of pre-existing mRNAs.

Kv4 potassium channel subunits control action potential repolarization and frequency‐dependent broadening in rat hippocampal CA1 pyramidal neurones

A-type potassium channels regulate neuronal firing frequency and the back-propagation of action potentials (APs) into dendrites of hippocampal CA1 pyramidal neurones. Recent molecular cloning studies have found several families of voltage-gated K(+) channel genes expressed in the mammalian brain. At present, information regarding the relationship between the protein products of these genes and the various neuronal functions performed by voltage-gated K(+) channels is lacking. Here we used a combination of molecular, electrophysiological and imaging techniques to show that one such gene, Kv4.2, controls AP half-width, frequency-dependent AP broadening and dendritic action potential propagation. Using a modified Sindbis virus, we expressed either the enhanced green fluorescence protein (EGFP)-tagged Kv4.2 or an EGFP-tagged dominant negative mutant of Kv4.2 (Kv4.2g(W362F)) in CA1 pyramidal neurones of organotypic slice cultures. Neurones expressing Kv4.2g(W362F) displayed broader action potentials with an increase in frequency-dependent AP broadening during a train compared with control neurones. In addition, Ca(2)(+) imaging of Kv4.2g(W362F) expressing dendrites revealed enhanced AP back-propagation compared to control neurones. Conversely, neurones expressing an increased A-type current through overexpression of Kv4.2 displayed narrower APs with less frequency dependent broadening and decreased dendritic propagation. These results point to Kv4.2 as the major contributor to the A-current in hippocampal CA1 neurones and suggest a prominent role for Kv4.2 in regulating AP shape and dendritic signalling. As Ca(2)(+) influx occurs primarily during AP repolarization, Kv4.2 activity can regulate cellular processes involving Ca(2)(+)-dependent second messenger cascades such as gene expression and synaptic plasticity.

Mechanism of impairment of long-term potentiation by amyloid β is independent of NMDA receptors or voltage-dependent calcium channels in hippocampal CA1 pyramidal neurons

β-Amyloid peptide (Aβ) is known to be involved in Alzheimer's disease (AD). Although the fibril form of Aβ is known to have neurotoxicity, it has been shown that not only the fibril form but also the oligomer form of Aβ may be related to the neuropathophysiology of AD, specifically to memory loss. Some studies have demonstrated that low concentrations of the Aβ oligomer impair long-term potentiation (LTP), a cellular model for learning and memory, after short exposure times in vivo and in vitro, although little is known about the mechanism involved in Aβ-mediated inhibition of LTP. In this study, we used the patch clamp whole-cell technique in rat hippocampal CA1 pyramidal neurons to study more precisely how the Aβ oligomer affects synaptic plasticity. The brief perfusion of slices with a low concentration (1 μM) of Aβ 1–42 significantly impaired LTP induction of the excitatory input. The same concentration of Aβ did not affect basal transmission or paired-pulse facilitation. We also demonstrated that neither NMDAR-EPSCs nor the voltage-depended calcium channel (VDCC) currents were affected by the same concentration of Aβ 1–42 as used in the LTP experiments. These data suggest that Aβ mediated impairment of LTP induction is independent of NMDARs or VDCCs.

Neuroprotective mechanisms of lidocaine against in vitro ischemic insult of the rat hippocampal CA1 pyramidal neurons

To compare neuroprotective effects of lidocaine and procaine against ischemic insult, intracellular recordings were made from rat hippocampal CA1 pyramidal neurons in slice preparations. Superfusion of the slices with oxygen- and glucose-deprived medium (in vitro ischemia) produced a rapid depolarization 6 min from the onset. When oxygen and glucose were reintroduced, the membrane depolarized further until it reached 0 mV, and thereafter the membrane showed no functional recovery. Pretreatment with lidocaine (10 μM), but not procaine (50 μM), restored the membrane potential after the reintroduction of oxygen and glucose. Lidocaine, compared to procaine, significantly inhibited the reduction in both tissue ATP content and flavoprotein fluorescence during and after in vitro ischemia. Under electron microscopy, only lidocaine well preserved the structure of mitochondria in the CA1 pyramidal cell body. Extracellular recordings revealed that procaine reduced the field postsynaptic potential whereas lidocaine augmented it. Both drugs reduced the presynaptic volley dose-dependently. Neither lidocaine nor procaine significantly affected a rapid rise of the intracellular Ca 2+ level produced by in vitro ischemia in the CA1 region. All the results suggest that the neuroprotective lidocaine action is due to the protection of the mitochondria to maintain the tissue ATP content during and after in vitro ischemia.

Effects of emodin on synaptic transmission in rat hippocampal CA1 pyramidal neurons in vitro

Rhubarb extracts provide neuroprotection after brain injury, but the mechanism of this protective effect is not known. The present study tests the hypothesis that rhubarb extracts interfere with the release of glutamate by brain neurons and, therefore, reduce glutamate excitotoxicity. To this end, the effects of emodin, an anthraquinone derivative extracted from Rheum tanguticum Maxim. Ex. Balf, on the synaptic transmission of CA1 pyramidal neurons in rat hippocampus were studied in vitro. The excitatory postsynaptic potential (EPSP) was depressed by bath-application of emodin (0.3–30 μM). Paired-pulse facilitation (PPF) of the EPSP was significantly increased by emodin. The monosynaptic inhibitory postsynaptic potential (IPSP) recorded in the presence of glutamate receptor antagonists (DNQX and AP5) was not altered by emodin. Emodin decreased the frequency, but not the amplitude, of the miniature EPSP (mEPSP). The inhibition of the EPSP induced by emodin was blocked by either 8-CPT, an adenosine A 1 receptor antagonist, or by adenosine deaminase. These results suggest that emodin inhibits the EPSP by decreasing the release of glutamate from Schaffer collateral/commissural terminals via the activation of adenosine A 1 receptors in rat hippocampal CA1 area and that the neuroprotective effects of rhubarb extracts may result from decreased glutamate excitotoxicity.

A Functional Study of Single Mammalian CNS “Synaptic Bouton”

Single CNS neurons could be dissociated with adherent functional synaptic boutons without using any enzyme, namely when preparing a “synaptic bouton.” This allows experimenters to investigate the effects of presynaptic modulators of synaptic transmission with unprecedented case and accuracy. Moreover, a single bouton can be visualized using fluorescent markers and can also be focally stimulated with electrical pulses. In this communication, high voltage-dependent Ca2+ channels of nerve endings, as one of experimental examples using the “synaptic bouton” preparation, are described. Ca2+ channels belonging to different subtypes, which trigger GABA release from nerve terminals (boutons) projecting to rat hippocampal CA1 pyramidal neurons, were studied. GABA-ergic evoked inhibitory postsynaptic currents (eIPSCs) were recorded; these currents were evoked by focal stimulation of single boutons in mechanically dissociated neurons and by stimulation of a nerve bundle in slice preparations. Nilvadipine, an L-type Ca2+ channel blocker, completely inhibited eIPSCs evoked by stimulation of single boutons but exerted no effect on eIPSCs evoked by low-frequency stimulation of the nerve bundle. Nilvadipine did, however, prevent potentiation of the eIPSC amplitude following high-frequency stimulation of the nerve bundles in slice preparations. ω-Conotoxin-GVIA, an N-type Ca2+ channel blocker, and ω-Agatoxin-IVA, a P/Q-type Ca2+ channel blocker, completely inhibited the eIPSCs in 33.3 and 83.3% of the recordings from single boutons, respectively. In response to low-frequency nerve bundle stimulation in the slice preparation, both ω-Conotoxin-GVIA and ω-Agatoxin-IVA partially reduced the amplitude of eIPSC, and the residual component could be abolished by Cd2+. From these results, the following hypotheses could be drawn. (i) The distribution of P/Q- and N-type Ca2+ channels at a single bouton is nonuniform; (ii) when a focal stimulation is applied to a single bouton, L-type Ca2+ channels play a significant role in generation of action potentials, which subsequently activate P/Q- and N-type Ca2+ channels at GABA release sites; and (iii) action potentials conducted through axons in the slice preparation are sufficient to depolarize the bouton membrane, even when L-type Ca2+ channels are suppressed.

Endogenous PGE2Regulates Membrane Excitability and Synaptic Transmission in Hippocampal CA1 Pyramidal Neurons

The significance of cyclooxygenases (COXs), the rate-limiting enzymes that convert arachidonic acid (AA) to prostaglandins (PGs) in the brain, is unclear, although they have been implicated in inflammatory responses and in some neurological disorders such as epilepsy and Alzheimer's disease. Recent evidence that COX-2, which is expressed in postsynaptic dendritic spines, regulates PGE2 signaling in activity-dependent long-term synaptic plasticity at hippocampal perforant path-dentate granule cell synapses, suggests an important role of the COX-2-generated PGE2 in synaptic signaling. However, little is known of how endogenous PGE2 regulates neuronal signaling. Here we showed that endogenous PGE2 selectively regulates fundamental membrane and synaptic properties in the hippocampus. Somatic and dendritic membrane excitability was significantly reduced when endogenous PGE2 was eliminated with a selective COX-2 inhibitor in hippocampal CA1 pyramidal neurons in slices. Exogenous application of PGE2 produced significant increases in frequency of firing, excitatory postsynaptic potentials (EPSP) amplitude, and temporal summation in slices treated with the COX-2 inhibitor. The PGE2-induced increase in membrane excitability seemed to result from its inhibition of the potassium currents, which in turn, boosted dendritic Ca2+ influx during dendritic-depolarizing current injections. In addition, the PGE2-induced enhancement of EPSPs was blocked by eliminating both PKA and PKC activities. These findings indicate that endogenous PGE2 dynamically regulates membrane excitability, synaptic transmission, and plasticity and that the PGE2-induced synaptic modulation is mediated via cAMP-PKA and PKC pathways in rat hippocampal CA1 pyramidal neurons.

Low affinity block of native and cloned hyperpolarization-activated Ih channels by Ba 2+ ions

Ba 2+ is commonly used to discriminate two classes of ion currents. The classical inward-rectifying K + current, I Kir, is blocked by low millimolar concentrations of Ba 2+, whereas the hyperpolarization-activated cation current, I h, is assumed not to be sensitive to Ba 2+. Here we investigated the effects of Ba 2+ on I h currents recorded from rat hippocampal CA1 pyramidal neurons, and on cloned I h channels composed of either HCN1 or HCN2 subunits transiently expressed in Human Embryonic Kidney (HEK) 293 cells. The results show that low millimolar concentrations of Ba 2+ reduce the maximal I h conductance (IC 50∼3–5 mM) in both CA1 pyramidal neurons and in HEK 293 cells without specificity for HCN1 or HCN2 subunits. In addition, Ba 2+ decreases the rate of activation and increases the rate of deactivation of I h currents. Neither the half-maximal voltage of activation, V h, nor the reversal potential of the I h channels were affected by Ba 2+. The combined results suggest that Ba 2+, at concentrations commonly used to block I Kir currents, also reduces the conductance of I h channels without subunit specificity, and affects the kinetics of I h channel gating.

A new cytochemical method for ultrastructural localization of Co 2+ in rat hippocampal CA1 pyramidal neurons in vitro

This paper describes new cytochemical method for the ultrastructural localization of Co 2+ following blockade of synaptic transmission. In the CA1 region of rat hippocampal slices, electrical stimulation of the Schaffer collaterals elicited field excitatory postsynaptic potentials (fEPSPs). The fEPSPs were completely blocked within 2 min after the addition of Co 2+ (2 mM). The slice was then fixed and precipitated Co 2+ was examined by means of a solution containing 2.5% glutaraldehyde and 10 mM K 3[Fe 3+(CN) 6] in 90 mM NaCl. Electron spectroscopic imaging confirmed Co in the precipitate. The precipitates were found as clusters on the membranes of the fine apical dendrites and their spine heads of CA1 pyramidal neurons. No clustered precipitate was found when slices were treated: (1) without Co 2+; (2) after recovery from the Co 2+-induced blockade of fEPSPs; (3) without electrical stimulation of the Schaffer collaterals; and (4) with dl-2-amino-5-phosphonopentanoate and 6-cyano-7-nitroquinoxaline-2,3-dione. After administrating glutamate (5 mM) in the presence of tetrodotoxin (1 μM) and Co 2+, precipitates were found on dendritic membranes and spine heads. These results indicate that the Schaffer collaterals stimulation induces the binding of Co 2+ on CA1 pyramidal neuron membrane.

5-HT 7 receptors increase the excitability of rat hippocampal CA1 pyramidal neurons

In the CA1 area of rat hippocampal slices, a combined application of 5-CT, a potent 5-HT 1A and 5-HT 7 receptor agonist, and WAY 100635, a selective 5-HT 1A receptor antagonist, resulted in a reversible increase of the CA1 extracellular population spike amplitude. In whole-cell recording from identified pyramidal neurons, the effects of 5-CT applied in the presence of WAY 100635 involved a reduction of the slow afterhyperpolarization (sAHP) and the frequency adaptation of action potential firing, which could be blocked by a specific 5-HT 7 receptor antagonist SB 269970. The results indicate that the activation of 5-HT 7 receptors increases the excitability of hippocampal CA1 pyramidal cells.

P.3.005 The aversive effect of a glutamate metabotropic receptor agonist injected into the dorsal periaqueductal grey may partially depend on glutamate release

The excitatory and inhibitory actions of metabotropic glutamate receptor (mGluR) agonists were investigated in acutely dissociated rat hippocampal CA3 pyramidal neurons, using the conventional whole-cell and nystatin-perforated patch recording configurations under the voltage-clamp condition. With the conventional whole-cell recording, glutamate (Glu) and quisqualic acid (QA) induced only ionotropic inward currents accompanied by increased membrane conductance at a holding potential (VH) of -45 mV. The response was reversibly blocked in the presence of D-2-amino-5-phosphonopentanoic acid (d-AP5) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), the antagonists ofN-methyl-d-aspartate (NMDA) receptor and non-NMDA receptor, respectively. With nystatin-perforated patch recording, mGlu responses insensitive to bothd-AP5 and CNQX were observed. Fifty-five % of the cells responded by a slow inward current accompanied by conductance decrease (ImGlui) at aVH of −44 mV. One % of the neurons showed an outward current with conductance increase (ImGluo), and 34% of the neurons showedImGluo followed byImGlui. The onset ofImGluo occurred approximately 900 ms after the response to 30 mM K+. The time to peak ofImGluo were 32- to 79-times longer than those of ionotropic responses.ImGlui appeared at lower concentrations than ionotropic Glu responses, whereasImGluo appeared at similar concentrations as ionotropic responses. The rank order of affinity was QA > Glu > (±)-1-aminocyclopentane-trans-1,3-dicar☐ylic acid (tACPD) for bothImGlui andImGluo. Half-maximal effective concentrations (EC50) and the threshold concentrations for the three agonists were four- to tenfold lower forImGlui than forImGluo. The current-voltage relationship showed that the reversal potentials ofImGlui andImGluo shifted 55 and 59 mV, respectively, for a tenfold change in extracellular K+ concentration, indicating that K+ is the charge carrier of both mGlu responses. DuringImGlui, both the leakage current and muscarine-sensitive voltage-dependent K+ current (M current) were suppressed.ImGluo induced by 10−4 M tACPD was abolished by 3 · 10−7 M charybdotoxin and 10−6 M ryanodine. These results show that there are two components of mGlu responses in CA3 pyramidal neurons and thatImGlui andImGluo show different pharmacological properties.

The action of BDNF on GABAA currents changes from potentiating to suppressing during maturation of rat hippocampal CA1 pyramidal neurons

The action of BDNF on GABAA currents changes from potentiating to suppressing during maturation of rat hippocampal CA1 pyramidal neurons