PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Pyramidal Cells”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1999

Transient potassium currents regulate the discharge patterns of dorsal cochlear nucleus pyramidal cells.

Pyramidal cells in the dorsal cochlear nucleus (DCN) show three distinct temporal discharge patterns in response to sound: "pauser," "buildup," and "chopper." Similar discharge patterns are seen in vitro and depend on the voltage from which the cell is depolarized. It has been proposed that an inactivating A-type K+ current (IKI) might play a critical role in generating the three different patterns. In this study we examined the characteristics of transient currents in DCN pyramidal cells to evaluate this hypothesis. Morphologically identified pyramidal cells in rat brain slices (P11-P17) exhibited the three voltage-dependent discharge patterns. Two inactivating currents were present in outside-out patches from pyramidal cells: a rapidly inactivating (IKIF, tau approximately 11 msec) current insensitive to block by tetraethylammonium (TEA) and variably blocked by 4-aminopyridine (4-AP) with half-inactivation near -85 mV, and a slowly inactivating TEA- and 4-AP-sensitive current (IKIS, tau approximately 145 msec) with half-inactivation near -35 mV. Recovery from inactivation at 34 degrees C was described by a single exponential with a time constant of 10-30 msec, similar to the rate at which first spike latency increases with the duration of a hyperpolarizing prepulse. Acutely isolated cells also possessed a rapidly activating (<1 msec at 22 degrees C) transient current that activated near -45 mV and showed half-inactivation near -80 mV. A model demonstrated that the deinactivation of IKIF was correlated with the discharge patterns. Overall, the properties of the fast inactivating K+ current were consistent with their proposed role in shaping the discharge pattern of DCN pyramidal cells.

4-Aminopyridine↗
PubMed2001

A physiologically based model of discharge pattern regulation by transient K+ currents in cochlear nucleus pyramidal cells.

Pyramidal cells in the dorsal cochlear nucleus (DCN) show three characteristic discharge patterns in response tones: pauser, buildup, and regular firing. Experimental evidence suggests that a rapidly inactivating K+ current (I(KIF)) plays a critical role in generating these discharge patterns. To explore the role of I(KIF), we used a computational model based on the biophysical data. The model replicated the dependence of the discharge pattern on the magnitude and duration of hyperpolarizing prepulses, and I(KIF) was necessary to convey this dependence. Phase-plane and perturbation analyses show that responses to depolarization are critically controlled by the amount of inactivation of I(KIF). Experimentally, half-inactivation voltage and kinetics of I(KIF) show wide variability. Varying these parameters in the model revealed that half-inactivation voltage, and activation and inactivation rates, controls the voltage and time dependence of the model cell discharge. This suggests that pyramidal cells can adjust their sensitivity to different temporal patterns of inhibition and excitation by modulating the kinetics of I(KIF). Overall, I(KIF) is a critical conductance controlling the excitability of DCN pyramidal cells.

Action Potentials↗
PubMed2002

Concordant and discordant coding of spatial location in populations of hippocampal CA1 pyramidal cells.

Pyramidal cells in the rat hippocampus commonly show place-related activity, but it has been difficult to understand the factors that govern them. A particularly important question is whether individual cells have identifiable correlates that can be manipulated independently of the correlates of other cells. Recently Tanila et al. examined the activity of small ensembles of hippocampal cells in rats running on a plus-maze with distinct intra- and extramaze cues. When the two sets of cues were rotated 90 degrees in opposite directions, some cells followed the intramaze cues, others followed the extramaze cues, and others "remapped" unpredictably; moreover, all possible combinations were seen within simultaneously recorded ensembles. In the current study, CA1 pyramidal cell population activity was recorded from four rats in a similar paradigm, using a recording system that permitted the analysis of ensembles of 4-70 simultaneously recorded units. The results were consistent with the data from the earlier study in showing an increase in remapping over time and in showing some place fields following one of the defined sets of cues while others remapped. When the possibility of random remapping was controlled for, however, the analysis did not show significant numbers of place fields following both sets of cues simultaneously. Furthermore, all rats initially showed fully concordant responses with all place fields following the local cues. For two rats, this pattern continued until a new configuration was introduced at which time all fields switched to follow the distal cues. Taken together, the results are difficult to reconcile with the hypothesis that individual hippocampal cells encode information about different subsets of cues in the environment.

Animals↗
PubMed2001

Excitatory synapses from CA3 pyramidal cells onto neighboring pyramidal cells differ from those onto inhibitory interneurons.

The glutamatergic pyramidal cell (PYR) to pyramidal cell synapse was compared to the PYR to inhibitory interneuron (INT) synapse in area CA3 of rat hippocampal roller-tube cultures. Paired-pulses and tetanic stimulations of a presynaptic PYR were conducted utilizing dual whole-cell patch-clamp recordings of either two PYRs or of a PYR and visually identified stratum oriens INT. Differences in synaptic characteristics were observed, depending on the postsynaptic target cell. Across cell pairs the variation of EPSC amplitudes was much larger for postsynaptic PYRs than for INTs. EPSCs recorded from INTs had faster rise times and shorter decays than those recorded in PYRs. There were also differences in the short-term plasticity of these synapses. Dual PYR:PYR recordings during paired-pulse stimulation at 100 ms interstimulus intervals demonstrated no modulation of EPSC amplitudes, while PYR:INT synapses showed paired-pulse depression. During trains of action potentials, the PYR:PYR EPSCs followed the presynaptic action potential train reliably, with little depression of EPSCs, while PYR:INT EPSCs demonstrated failures of transmission or profound depression after the initial EPSC. These results indicate multiple differences at both the pre- and postsynaptic level in the characteristics of pyramidal cell synapses that depend on the postsynaptic target's identity as either PYR or INT.

Action Potentials↗
PubMed1999

Apamin-sensitive conductance mediates the K(+) current response during chemical ischemia in CA3 pyramidal cells.

Pyramidal cells typically respond to ischemia with initial transient hyperpolarization, which may represent a neuroprotective response. To identify the conductance underlying this hyperpolarization in CA3 pyramidal neurons of rat hippocampal organotypic slice cultures, recordings were obtained using the single-electrode voltage-clamp technique. Brief chemical ischemia (2 mM 2-deoxyglucose and 3 mM NaN(3), for 4 min) induced a response mediated by an increase in K(+) conductance. This current was blocked by intracellular application of the Ca(2+) chelator, bis-(o-aminophenoxy)-N,N,N', N'-tetraacetic acid (BAPTA), reduced with low external [Ca(2+)], and inhibited by a selective L-type Ca(2+) channel inhibitor, isradipine, consistent with the activation of a Ca(2+)-dependent K(+) conductance. Experiments with charybdotoxin (10 nM) and tetraethylammonium (TEA; 1 mM), or with the protein kinase C activator, phorbol 12,13-diacetate (PDAc; 3 microM), ruled out an involvement of a large conductance-type or an apamin-insensitive small conductance, respectively. In the presence of apamin (1 microM), however, the outward current was significantly reduced. These results demonstrate that in rat hippocampal CA3 pyramidal neurons an apamin-sensitive Ca(2+)-dependent K(+) conductance is activated in response to brief ischemia generating a pronounced outward current.

ATP-Binding Cassette Transporters↗
PubMed2006

Postsynaptic origin of CB1-dependent tonic inhibition of GABA release at cholecystokinin-positive basket cell to pyramidal cell synapses in the CA1 region of the rat hippocampus.

Cholecystokinin-positive (CCK+) basket cells are a major source of perisomatic GABAergic inputs to CA1 pyramidal cells. These interneurons express high levels of presynaptic cannabinoid type 1 (CB1) receptors that mediate short-term depression of GABA release following depolarization of postsynaptic cells. However, it is not known whether GABA release from CA1 CCK+ basket cells is under tonic endocannabinoid inhibition. In paired patch-clamp recordings, action potentials in presynaptic CCK+ basket cells evoked large IPSCs with fast kinetics in pyramidal cells. The proportion of action potentials that failed to evoke GABA release varied markedly between pairs, from highly reliable to virtually silent connections. Application of the CB1 receptor antagonist AM251 (10 microm) decreased the proportion of failures, revealing a persistent suppression of synaptic transmission by CB1 receptors. However, AM251 had no significant effect on the failure rate when the calcium chelator BAPTA (10 mm) was introduced into the postsynaptic cell, indicating that the tonic inhibition of GABA release by CB1 receptors is homosynaptically controlled by the postsynaptic cell, and that it is not due to constitutive CB1 receptor activity. Application of muscarinic or metabotropic glutamate receptor agonists inhibited synaptic transmission exclusively through the release of endocannabinoids from postsynaptic cells in a manner that could not be blocked by postsynaptic BAPTA, and had no direct effect on transmission. In contrast, GABA(B) receptor activation directly blocked GABA release, but there was no evidence for tonic inhibition of GABA release by GABA(B) receptors. Neither serotonergic nor mu-opioid agonists had significant influence on GABA release from CCK+ axon terminals. These results reveal that GABA release from CA1 CCK+ basket cells is under homosynaptic tonic inhibition by endocannabinoids, and it is subject to both direct and indirect modulation by various G-protein-dependent neuromodulators.

Animals↗
PubMed2005

Differential responses to NMDA receptor activation in rat hippocampal interneurons and pyramidal cells may underlie enhanced pyramidal cell vulnerability.

Hippocampal interneurons are generally more resistant than pyramidal cells to excitotoxic insults. Because NMDA receptors play a crucial role in neurodegeneration, we have compared the response to exogenous NMDA in CA1 pyramidal cells and interneurons of the stratum oriens using combined whole-cell patch-clamp recording and ratiometric Ca2+ imaging. In voltage-clamp, current-clamp or in nominally Mg2+-free medium, NMDA (10 microM; 3-5 min exposure in the presence of tetrodotoxin) induced a markedly larger inward current and Ca2+ rise in pyramidal cells than in interneurons. Pyramidal cells also showed a more pronounced voltage dependence in their response to NMDA. We hypothesized that this enhanced response to NMDA receptor activation in pyramidal cells could underlie their increased vulnerability to excitotoxicity. Using loss of dye as an indicator of degenerative membrane disruption, interneurons tolerated continuous exposure to a high concentration of NMDA (30 microM) for longer periods than pyramidal cells. This acute neurodegeneration in pyramidal cells was independent of intracellular Ca2+, because high intracellular BAPTA (20 mM) did not prolong survival time. Thus, a plausible explanation for the enhanced sensitivity of pyramidal neurons to excitotoxic insults associated with cerebral ischemia is their greater response to NMDA receptor activation, which may reflect differences in NMDA receptor expression and/or subunit composition.

Anesthetics, Local↗
PubMed1985

Ratio of pyramidal cells versus non-pyramidal cells in sector CA1 of the human Ammon's horn.

Combined Golgi/pigment studies revealed that pyramidal neurons and non-pyramidal cells of the Ammon's horn of the human adult can be distinguished from each other by their characteristic lipofuscin pigment deposits. In sector CA1, both the typical pyramidal neurons and the modified forms of pyramidal cells contain a modest amount of fine lipofuscin granules while non-pyramidal cells are either pigment-laden or devoid of lipofuscin deposits. Strips running through the whole depth of the pyramidal cell layer and the stratum oriens of CA1 were examined and all nucleolated nerve cells present within these strips were classified and counted (16 brains, age range from 28 to 69 years). Of the 18,510 neurons classified, 16,765 were pyramidal cells, including their modified versions, and 1,745 were non-pyramidal cells. The pyramidal cells, accordingly, were intermixed with 9.4 +/- 1.0% non-pyramidal neurons. The data presented provide a basis for investigation of the aging and diseased human brain.

Adult↗
PubMed1993

A comparison of rat hippocampal mossy cells and CA3c pyramidal cells.

1. There is a long-standing debate about whether the large spiny cells in the hilar region of the hippocampus should be classified as pyramidal cells of Ammon's horn or as a distinct cell type of the dentate gyrus. The rationale for grouping these hilar neurons (termed "mossy cells") with pyramidal cells of Ammon's horn is shared characteristics. In the present study we have compared the morphological and physiological characteristics of mossy cells and nearby CA3c pyramidal cells with the use of a rat hippocampal slice preparation. 2. Biocytin-labeled neurons were examined on the basis of soma area, location, shape, number of primary dendrites, extent of dendritic spines, dendritic location, and axon trajectories. Mossy cells had larger soma areas than CA3c pyramidal cells, and they had more large complex spines (thorny excrescences) on their proximal dendrites and somata than CA3c pyramidal cells. Mossy cell dendritic trees and axon collaterals ramified in different regions of the hippocampus than dendrites and axons of CA3c pyramidal cells. 3. Intrinsic physiological properties, and spontaneous and evoked synaptic properties, were measured and compared. Mossy cells had significantly higher input resistances, smaller amplitude burst afterhyperpolarizations, smaller amplitude action potentials, less spike-frequency adaptation, and more anomalous rectification than CA3c pyramidal cells. 4. Mossy cells had spontaneous excitatory postsynaptic potentials (EPSPs) that were significantly higher in frequency and larger in amplitude than CA3c pyramidal cells. A larger proportion of mossy cells than CA3c pyramidal cells responded to perforant path stimulation with depolarizing postsynaptic potentials without any apparent hyperpolarization. Conversely, a smaller proportion of mossy cells than CA3c pyramidal cells responded to perforant path stimulation with inhibitory postsynaptic potentials (IPSPs), and spontaneous IPSPs were more difficult to detect in mossy cells. 5. The intrinsic physiological properties of mossy cells endow these cells with potent excitatory mechanisms but relatively fewer inhibitory control processes than CA3c pyramidal cells. Recordings of spontaneous and evoked PSPs suggest that mossy cells receive more excitatory input and less inhibitory input than CA3c pyramidal cells. These intrinsic and synaptic properties of mossy cells may explain this cell type's exceptional vulnerability to excitotoxic damage by intense afferent stimulation. 6. In summary, mossy cells were significantly different from CA3c pyramidal cells in many of their morphological, intrinsic physiological, and synaptic properties.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed2000

Gq protein alpha subunits Galphaq and Galpha11 are localized at postsynaptic extra-junctional membrane of cerebellar Purkinje cells and hippocampal pyramidal cells.

Following cell surface receptor activation, the alpha subunit of the Gq subclass of GTP-binding proteins activates the phosphoinositide signalling pathway. Here we examined the expression and localization of Gq protein alpha subunits in the adult mouse brain by in situ hybridization and immunohistochemistry. Of the four members of the Gq protein alpha subunits, Galphaq and Galpha11 were transcribed predominantly in the brain. The highest transcriptional level of Galphaq was observed in cerebellar Purkinje cells (PCs) and hippocampal pyramidal cells, while that of Galpha11 was noted in hippocampal pyramidal cells. Antibody against the C-terminal peptide common to Galphaq and Galpha11 strongly labelled the cerebellar molecular layer and hippocampal neuropil layers. In these regions, immunogold preferentially labelled the cytoplasmic face of postsynaptic cell membrane of PCs and pyramidal cells. Immunoparticles were distributed along the extra-junctional cell membrane of spines, dendrites and somata, but were almost excluded from the junctional membrane. By double immunofluorescence, Galphaq/Galpha11 was extensively colocalized with metabotropic glutamate receptor mGluR1alpha in dendritic spines of PCs and with mGluR5 in those of hippocampal pyramidal cells. Together with concentrated localization of mGluR1alpha and mGluR5 in a peri-junctional annulus on PC and pyramidal cell synapses (Baude et al. 1993, Neuron, 11, 771-787; Luján et al. 1996, Eur. J. Neurosci., 8, 1488-1500), the present molecular-anatomical findings suggest that peri-junctional stimulation of the group I metabotropic glutamate receptors is mediated by Galphaq and/or Galpha11, leading to the activation of the intracellular effector, phospholipase Cbeta.

Amino Acid Sequence↗
PubMed1985

The neuronal composition of area 17 of rat visual cortex. I. The pyramidal cells.

The pyramidal cells in area 17 of rat visual cortex have been examined by light microscopy using Golgi preparations and semithin plastic sections, and by electron microscopy. Pyramidal cells have cell bodies in layers II-VIa. The pyramidal cells in the lower portion of layer II/III are typical examples of this neuronal type in that they have pyramidal-shaped cell bodies, apical dendrites which ascend to layer I, and a skirt of basal dendrites. The pyramidal cells in upper layer II/III are similar in form but have shorter apical dendrites, while the most superficial pyramidal cells lack apical dendrites and instead have two or more primary dendrites that emanate from the upper surface of their somata. In layer V the pyramidal cells are of two sizes, medium and large, and both have a typical morphology, although the larger neurons have thicker apical dendrites and better-developed axon hillocks than the medium-sized pyramids. The medium-sized pyramidal cells of layer V outnumber the large ones to a ratio of 2.5:1. In layer IV a few typical medium-sized pyramidal cells are present, but the majority are small and can be regarded as star pyramids for they have dendrites radiating in all directions. No clearly identified spiny stellate cells have been encountered in layer IV. The pyramidal cells of layer VIa are also small, and most of them have apical dendrites which only ascend as far as layer IV. In addition to these varieties, both inverted and horizontally inclined pyramidal cells have been encountered. In electron micrographs it is apparent that although all of the pyramidal cells have symmetric axosomatic synapses, the frequency with which these synapses occur varies. The cell bodies of the various forms of pyramidal cells do not show a standard cytology. The medium-sized pyramidal cells of layer II/III usually have rounded nuclei, while the nuclei of the small pyramidal cells of layers IV and VIa are somewhat more irregular, and the large pyramidal cells of layer V have deeply indented nuclear envelopes. The appearance of the perikaryal cytoplasm also varies. The larger pyramidal cells have numerous mitochondria and well-developed Nissl bodies in their perikaryal cytoplasm, but the smaller cells have much-less-pronounced mitochondria and their rough endoplasmic reticulum is only organized into stacks at the bases of dendrites. Pyramidal cells account for about 87% of profiles of neuronal cell bodies with nuclei in layer II/III, 90% in layer IV, 89% in layer V, and 97% in layer VIa.

Animals↗
PubMed2001

Intracellular recording and labeling of mossy cells and proximal CA3 pyramidal cells in macaque monkeys.

Little is known about the morphological characteristics and intracellular electrophysiological properties of neurons in the primate hippocampus and dentate gyrus. We have therefore begun a program of studies using intracellular recording and biocytin labeling in hippocampal slices from macaque monkeys. In the current study, we investigated mossy cells and proximal CA3 pyramidal cells. As in rats, macaque mossy cells display fundamentally different traits than proximal CA3 pyramidal cells. Interestingly, macaque mossy cells and CA3 pyramidal neurons display some morphological differences from those in rats. Macaque monkey mossy cells extend more dendrites into the molecular layer of the dentate gyrus, have more elaborate thorny excrescences on their proximal dendrites, and project more axon collaterals into the CA3 region. In macaques, three types of proximal CA3 pyramidal cells are found: classical pyramidal cells, neurons with their dendrites confined to the CA3 pyramidal cell layer, and a previously undescribed cell type, the "dentate" CA3 pyramidal cell, whose apical dendrites extend into and ramify within the hilus, granule cell layer, and molecular layer of the dentate gyrus. The basic electrophysiological properties of mossy cells and proximal CA3 cells are similar to those reported for the rodent. Mossy cells have a higher frequency of large amplitude spontaneous depolarizing postsynaptic potentials, and proximal CA3 pyramidal cells are more likely to discharge bursts of action potentials. Although mossy cells and CA3 pyramidal cells in macaque monkeys display many morphological and electrophysiological features described in rodents, these findings highlight significant species differences, with more heterogeneity and the potential for richer interconnections in the primate hippocampus.

Animals↗
PubMed2005

LOXL null mice demonstrate selective dentate structural changes but maintain dentate granule cell and CA1 pyramidal cell potentiation in the hippocampus.

Lysyl oxidase-like protein (LOXL), part of the lysyl oxidase copper-dependent amine oxidase family, is expressed in the extracellular matrix and in the nucleus. It likely plays a role in cross-linking collagen and elastin, possibly modulating cellular functions. Immunohistochemical studies show the presence of LOXL in the pyramidal cell layer of the hippocampus; and in this study, we report that cells in the granule cell layer have significantly smaller somas in LOXL -/- compared to LOXL +/+ mice. In addition we tested the hypothesis that these structural alterations in the dentate granule layer were associated with synaptic efficacy and thus muted long-term potentiation in mice lacking the protein. Electrical recordings were obtained in 300-mum hippocampal slices in dentate and CA1 pyramidal cell layers in age-matched wild type and LOXL null mice. Potentiation in the CA1 cell layer of 10 LOXL -/- and 8 LOXL +/+ mice was 191.0+/-9.3% and 181.6+/-9.1%, respectively (mean+/-S.E.M.). Dentate potentiation was 120.8+/-7.0% and 121.0+/-3.4% in 11 LOXL -/- and 11 LOXL +/+ mice, respectively. No phenotypic difference in potentiation of population spike amplitude (or in EPSP slope) in either layer was observed. Thus, contrary to expectation, structural changes in the hippocampus of LOXL -/- mice did not affect synaptic remodeling in a manner that impaired the establishment of LTP.

Amino Acid Oxidoreductases↗
PubMed1994

EPSPs of dentate gyrus granule cells during epileptiform bursts of dentate hilar "mossy" cells and area CA3 pyramidal cells in disinhibited rat hippocampal slices.

When hippocampal slices are exposed to GABAA antagonists, area CA3 pyramidal cells and dentate hilar "mossy" cells discharge in synchronized epileptiform bursts (Müller and Misgeld, 1991; Scharfman, 1994b). Dentate interneurons are excited simultaneously, but the degree of discharge varies (Scharfman, 1994b). This study primarily examined the activity of dentate granule cells simultaneous to the epileptiform bursts of pyramidal cells and mossy cells. EPSPs followed by large GABAB receptor-mediated IPSPs were generated in granule cells during all epileptiform bursts of pyramidal cells and mossy cells, regardless of whether they were evoked or spontaneous. By simultaneous recording it was determined that granule cell EPSPs began several milliseconds after the start of pyramidal cell bursts (n = 48 simultaneous recordings) and immediately after the first action potential of a mossy cell burst (n = 77). Interneurons were similar to granule cells in the timing of their depolarizations relative to the onset of pyramidal cell (n = 24; Scharfman, 1994b) and mossy cell (n = 9) bursts. All excitatory activity was blocked by bath application of the glutamatergic AMPA/kainate receptor antagonist CNQX (5 microM, n = 5), but not the NMDA receptor antagonist D-APV (25-50 microM, n = 9). Granule cell EPSPs were decreased after focal application of CNQX to the molecular layer at a site close to the impaled granule cell (n = 5), whereas D-APV had no effect (n = 3). EPSPs also decreased after focal application of CNQX to the hilus, in two of four slices tested. The extracellularly recorded EPSP of granule cells was maximal in the inner molecular layer (n = 33), the site of the mossy cell axonal plexus. Severing the junction of the dentate gyrus and area CA3 blocked all spontaneous and evoked activity of dentate neurons without affecting burst discharges in area CA3a and CA3b (n = 6). None of the excitatory activity of any cell type was affected by cholinergic antagonists (atropine and mecamylamine, 25 microM each, n = 5; pirenzipine and dihydro-beta-erythroidine, 25 microM each, n = 5). The results suggest that there is a glutamatergic, AMPA/kainate receptor-mediated, excitatory pathway from area CA3 to the dentate gyrus in disinhibited slices. The pharmacological results, analyses of latency, as well as the known axonal projections of the sampled cells, suggest that the excitatory pathway begins within area CA3 and leads to granule cells via mossy cells. The data also suggest that dentate interneurons are excited by mossy cells, and possibly by pyramidal cells as well.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed2001

Coincident spiking activity induces long-term changes in inhibition of neocortical pyramidal cells.

In pyramidal cells, induction of long-term potentiation (LTP) and long-term depression (LTD) of excitatory synaptic transmission by coincidence of presynaptic and postsynaptic activity is considered relevant to learning processes in vivo. Here we show that temporally correlated spiking activity of a pyramidal cell and an inhibiting interneuron may cause LTD or LTP of unitary IPSPs. Polarity of change in synaptic efficacy depends on timing between Ca(2+) influx induced by a backpropagating train of action potentials (APs) in pyramidal cell dendrites (10 APs, 50 Hz) and subsequent activation of inhibitory synapses. LTD of IPSPs was induced by synaptic activation in the vicinity of the AP train (<300 msec relative to the beginning of the train), whereas LTP of IPSPs was initiated with more remote synaptic activation (>400 msec relative to the beginning of the AP train). Solely AP trains induced neither LTP nor LTD. Both LTP and LTD were prevented by 5 mm BAPTA loaded into pyramidal cells. LTD was prevented by 5 mm EGTA, whereas EGTA failed to affect LTP. Synaptic plasticity was not dependent on activation of GABA(B) receptors. It was also not affected by the antagonists of vesicular exocytosis, botulinum toxin D, and GDP-beta-S.

Action Potentials↗
PubMed1999

Functional GABAA receptor heterogeneity of acutely dissociated hippocampal CA1 pyramidal cells.

CA1 pyramidal cells were voltage clamped, and GABA was applied to individual cells with a modified U-tube, rapid drug application system. With Vh = -50 mV, inward currents elicited by 10 microM GABA were inhibited by GABAA receptor (GABAR) antagonists and were baclofen insensitive, suggesting that GABA actions on isolated CA1 pyramidal cells were GABAR mediated. GABA concentration-response curves averaged from all cells were fitted best with a two-site equation, indicating the presence of at least two GABA binding sites, a higher-affinity site (EC50-1 = 11.0 microM) and a lower-affinity site (EC50-2 = 334.2 microM), on two or more populations of cells. The effects of GABAR allosteric modulators on peak concentration-dependent GABAR currents were complex and included monophasic (loreclezole) or multiphasic (diazepam) enhancement, mixed enhancement/inhibition (DMCM, zolpidem) or multiphasic inhibition (zinc). Monophasic (70% of cells) or biphasic (30% of cells) enhancement of GABAR currents by diazepam suggested three different sites on GABARs (EC50-1 =1.8 nM; EC50-2 = 75.8 nM; EC50-3 = 275.9 nM) revealing GABAR heterogeneity. The imidazopyridine zolpidem enhanced GABAR currents in 70% of cells with an EC50 = 222.5 nM, suggesting a predominance of moderate affinity alpha2 (or alpha3-) subtype-containing BZ Type IIA receptors. A small fraction of cells (10%) had a high affinity for zolpidem, something that is suggestive of alpha1 subtype-containing BZ Type I receptors. The remaining 30% of cells were insensitive to or inhibited by zolpidem, suggesting the presence of alpha5 subtype-containing BZ Type IIB receptors. Whether BZ Type I and Type II receptors coexist could not be determined. The beta-carboline methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) inhibited GABAR currents in all cells at midnanomolar concentrations, but in addition, potentiated GABAR currents in some cells at low nanomolar concentrations, characterizing two groups of cells, the latter likely due to functional assembly of alpha5betaxgamma2GABARs. In all cells, GABAR currents were moderately sensitive (EC50 = 9 microM) to loreclezole, consistent with a relatively greater beta3 subtype, than beta1 subtype, subunit mRNA expression. Two populations of cells were identified based on their sensitivities to zinc(IC50 = 28 and 182 microM), suggesting the presence of at least two GABAR isoforms including alpha5beta3gamma2 GABARs. Consistent with the heterogeneity of expression of GABAR subunit mRNA and protein in the hippocampus and based on their differential responses to GABA and to allosteric modulators, distinct populations of CA1 pyramidal cells likely express multiple, functional GABAR isoforms.

Allosteric Regulation↗
PubMed2001

Temporal interaction between single spikes and complex spike bursts in hippocampal pyramidal cells.

Cortical pyramidal cells fire single spikes and complex spike bursts. However, neither the conditions necessary for triggering complex spikes, nor their computational function are well understood. CA1 pyramidal cell burst activity was examined in behaving rats. The fraction of bursts was not reliably higher in place field centers, but rather in places where discharge frequency was 6-7 Hz. Burst probability was lower and bursts were shorter after recent spiking activity than after prolonged periods of silence (100 ms-1 s). Burst initiation probability and burst length were correlated with extracellular spike amplitude and with intracellular action potential rising slope. We suggest that bursts may function as "conditional synchrony detectors," signaling strong afferent synchrony after neuronal silence, and that single spikes triggered by a weak input may suppress bursts evoked by a subsequent strong input.

Action Potentials↗