Action Potentials In Pyramidal Cells Research Articles

Dynamic Recovery from Depression Enables Rate Encoding in Inhibitory Synapses.

SummaryParvalbumin-expressing fast-spiking interneurons (PV-INs) control network firing and the gain of cortical response to sensory stimulation. Crucial for these functions, PV-INs can sustain high-frequency firing with no accommodation. However, PV-INs also exhibit short-term depression (STD) during sustained activation, largely due to the depletion of synaptic resources (vesicles). In most synapses the rate of replenishment of depleted vesicles is constant, determining an inverse relationship between depression levels and the activation rate, which theoretically, severely limits rate-coding capabilities. We examined STD of the PV-IN to pyramidal cell synapse in the mouse visual cortex and found that in these synapses the recovery from depression is not constant but increases linearly with the frequency of use. By combining modeling, dynamic clamp, and optogenetics, we demonstrated that this recovery enables PV-INs to reduce pyramidal cell firing in a linear manner, which theoretically is crucial for controlling the gain of cortical visual responses.

Regulation of single spike initiated feed-forward networks through 5-HT-2 receptors in the human and rat cerebral cortex

Event Abstract Back to Event Regulation of single spike initiated feed-forward networks through 5-HT-2 receptors in the human and rat cerebral cortex Gergely Komlosi1*, Gabor Molnar1, Noemi Molnar1, Szabolcs Olah1, Miklos Fule1, Pal Barzo2 and Gabor Tamas1 1 Research Group for Cortical Microcircuits of the Hungarian Academy of Sciences, University of Szeged, Hungary 2 Department of Neurosurgery, University of Szeged, Hungary The performance of the human cerebral cortex is unparalleled by the nervous system of other species and this is presumably supported by refined, but largely unknown features of the human microcircuit. We have shown that single action potentials in pyramidal cells can trigger reliable and stereotyped series of multiple postsynaptic potentials in simultaneously recorded pyramidal cells and interneurons in the human cerebral cortex. These polysynaptic event series are composed of alternating excitatory and inhibitory postsynaptic potentials lasting up to tens of milliseconds. We tested how these complex network events could be affected by ascending neurotransmitter systems. We recorded from pairs, triplets and quadruplets of neurons in slices of human association cortices and examined the effects of acetylcholine, dopamine and serotonin receptor agonists. Nanomolar concentrations of serotonin reversibly supressed single pyramidal spike activated di- and polysynaptic events, while other agonists exerted little or no effect. The effect of serotonin (100nM) could be enhanced by Fluoxetine used in therapeutic concentration (10M). Similarly, serotonin was effective in eliminating polysynaptic event series triggered by human axo-axonic cells. The effect of serotonin could be mimicked by the 5-HT-2 receptor agonist alpha-methylserotonin. We then investigated the effect of serotonin and alpha-methylserotonin on monosynaptic unitary connections between various types of layer 2/3 neurons both in human and rat. We found that alpha-methylserotonin decreased the amplitude of EPSPs between pyramidal and fast-spiking cells including basket and axo-axonic cells but did not change the amplitude of IPSPs from fast-spiking to pyramidal neurons. Alpha-methylserotonin increased the failure rate of the EPSPs suggesting a presynaptic site of modulation of serotonin in the glutamatergic synaptic transmission. In conclusion, activation of 5-HT2 receptors can eliminate pyramidal cell activated feed-forward network events presumably via downregulation of glutamate release probability in pyramidal axon terminals. Conference: 12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009. Presentation Type: Poster Presentation Topic: Research on the cerebral cortex and related structures Citation: Komlosi G, Molnar G, Molnar N, Olah S, Fule M, Barzo P and Tamas G (2009). Regulation of single spike initiated feed-forward networks through 5-HT-2 receptors in the human and rat cerebral cortex. Front. Syst. Neurosci. Conference Abstract: 12th Meeting of the Hungarian Neuroscience Society. doi: 10.3389/conf.neuro.01.2009.04.206 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 06 Mar 2009; Published Online: 06 Mar 2009. * Correspondence: Gergely Komlosi, Research Group for Cortical Microcircuits of the Hungarian Academy of Sciences, University of Szeged, Szeged, Hungary, komgeri@bio.u-szeged.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Gergely Komlosi Gabor Molnar Noemi Molnar Szabolcs Olah Miklos Fule Pal Barzo Gabor Tamas Google Gergely Komlosi Gabor Molnar Noemi Molnar Szabolcs Olah Miklos Fule Pal Barzo Gabor Tamas Google Scholar Gergely Komlosi Gabor Molnar Noemi Molnar Szabolcs Olah Miklos Fule Pal Barzo Gabor Tamas PubMed Gergely Komlosi Gabor Molnar Noemi Molnar Szabolcs Olah Miklos Fule Pal Barzo Gabor Tamas Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Dendritic release of glutamate suppresses synaptic inhibition of pyramidal neurons in rat neocortex.

Dual whole-cell recordings were made in layer 2/3 of the rat neocortex in synaptically connected pyramidal cells and fast-spiking non-accommodating (FSN) interneurons. In 75% of cell pairs (n = 80), the cells formed reciprocal synaptic connections. Trains of backpropagating action potentials in pyramidal cells induced Ca2+ transients in dendrites followed by inhibition of unitary IPSPs. IPSP depression was prevented by loading pyramidal cells with 5 mM BAPTA or EGTA. IPSP depression was mimicked by the metabotropic glutamate receptor (mGluR) agonist ACPD and was prevented by a mixture of the mGluR antagonists CPCCOEt and EGLU.IPSP depression was prevented by loading pyramidal cells with the antagonists of vesicular exocytosis botulinum toxin D (light chain) and GDP-beta-S. It is concluded that Ca2+-dependent release of a retrograde messenger, most probably glutamate, from pyramidal cell dendrites suppresses the inhibition of pyramidal neurons via activation of mGluRs located in FSN interneuron nerve terminals.

Interdependence of Multiple Theta Generators in the Hippocampus: a Partial Coherence Analysis

The extracellularly recorded theta oscillation reflects a dynamic interaction of various synaptic and cellular mechanisms. Because the spatially overlapping dipoles responsible for the generation of theta field oscillation may represent different mechanisms, their separation might provide clues with regard to their origin and significance. We used a novel approach, partial coherence analysis, to reveal the various components of the theta rhythm and the relationship among its generators. Hippocampal field activity was recorded by a 16-site silicon probe in the CA1-dentate gyrus axis of the awake rat. Field patterns, recorded from various intrahippocampal or entorhinal cortex sites, were used to remove activity caused by a common source by the partialization procedure. The findings revealed highly coherent coupling between theta signals recorded (1) from the hippocampal fissure and stratum (str.) oriens of the CA1 region and (2) between CA1 stratum radiatum and the dentate molecular layer. The results of partial coherence analysis indicated that rhythmic input from the entorhinal cortex explained theta coherence between signals recorded from the hippocampal fissure and str. oriens but not the coherence between signals derived from str. radiatum and the dentate molecular layer. After bilateral lesions of the entorhinal cortex, all signals recorded from both below and above the CA1 hippocampal pyramidal cell layer became highly coherent. These observations indicate the presence of two, relatively independent, theta generators in the hippocampus, which are mediated by the entorhinal cortex and the CA3-mossy cell recurrent circuitry, respectively. The CA3-mossy cell theta generator is partially suppressed by the dentate gyrus interneuronal output in the intact brain. We suggest that timing of the action potentials of pyramidal cells during the theta cycle is determined by the cooperation between the active CA3 neurons and the entorhinal input.

Target-cell-specific facilitation and depression in neocortical circuits.

In neocortical circuits, repetitively active neurons evoke unitary postsynaptic potentials (PSPs) whose peak amplitudes either increase (facilitate) or decrease (depress) progressively. To examine the basis for these different synaptic responses, we made simultaneous recordings from three classes of neurons in cortical layer 2/3. We induced repetitive action potentials in pyramidal cells and recorded the evoked unitary excitatory (E)PSPs in two classes of GABAergic neurons. We observed facilitation of EPSPs in bitufted GABAergic interneurons, many of which expressed somatostatin immunoreactivity. EPSPs recorded from multipolar interneurons, however, showed depression. Some of these neurons were immunopositive for parvalbumin. Unitary inhibitory (I)PSPs evoked by repetitive stimulation of a bitufted neuron also showed a less pronounced but significant difference between the two target neurons. Facilitation and depression involve presynaptic mechanisms, and because a single neuron can express both behaviors simultaneously, we infer that local differences in the molecular structure of presynaptic nerve terminals are induced by retrograde signals from different classes of target neurons. Because bitufted and multipolar neurons both formed reciprocal inhibitory connections with pyramidal cells, the results imply that the balance of activation between two recurrent inhibitory pathways in the neocortex depends on the frequency of action potentials in pyramidal cells.

Different mechanisms underlying the repolarization of narrow and wide action potentials in pyramidal cells and interneurons of cat motor cortex.

Two different types of action potentials were observed among the pyramidal cells and interneurons in cat motor cortex: the narrow action potentials and the wide action potentials. These two types of action potentials had similar rising phases (528.8 +/- 77.0 vs 553.1 +/- 71.8 mV/ms for the maximal rising rate), but differed in spike duration (0.44 +/- 0.09 vs 1.40 +/- 0.39 ms) and amplitude (57.31 +/- 8.22 vs 72.52 +/- 8.31 mV), implying that the ionic currents contributing to repolarization of these action potentials are different. Here we address this issue by pharmacological manipulation and using voltage-clamp technique in slices of cat motor cortex. Raising extracellular K+ concentration (from 3 mM to 10 mM), applying a low dose of 4-aminopyridine (2-200 microM) or administering a low concentration of tetraethylammonium (0.2-1.0 mM) each not only broadened the narrow action potentials, but also increased their amplitudes. In contrast, high K+ medium or low dose of tetraethylammonium only broadened the wide action potentials, leaving their amplitudes unaffected, and 4-aminopyridine had only a slight broadening effect on the wide spikes. These results implied that K+ currents were involved in the repolarization of both types of action potentials, and that the K+ currents in the narrow action potentials seemed to activate much earlier than those in the wide spikes. This early activated K+ current may counteract the rapid sodium current, yielding the extremely brief duration and small amplitude of the narrow spikes. The sensitivity of the narrow spikes to 4-aminopyridine may not be mainly attributed to blockade of the classical A current (IA), because depolarizing the membrane potential to inactivate IA did not reproduce the effects of 4-aminopyridine. Blockade of Ca2+ influx slowed the last two-thirds repolarization of the wide action potentials. On the contrary, the narrow action potentials were not affected by Ca(2+)-current blockers, but if they were first broadened by 4-aminopyridine or tetraethylammonium, subsequent application of Ca(2+)-free medium caused further broadening, suggesting that the narrow action potentials were too brief to activate the Ca(2+)-activated potassium currents for their repolarization. Therefore, the effects of low concentrations of tetraethylammonium on the narrow spikes appeared to be mainly due to blockade of an outward current that was different from the tetraethylammonium-sensitive Ca(2+)-activated potassium current (IC). In the neurons with the narrow spikes, voltage-clamp experiments revealed two voltage-gated outward currents that were sensitive to tetraethylammonium and 4-aminopyridine, respectively. Both currents were activated rapidly following the onset of depolarizing steps. Interestingly, the tetraethylammonium-sensitive current was a transient outward current that inactivated rapidly (tau < or = 5 ms), while the 4-aminopyridine-sensitive current was relatively persistent during maintained depolarization. The 4-aminopyridine-sensitive current did not show obvious inactivation even at membrane potential of -40 mV, which completely inactivated the transient tetraethylammonium-sensitive, current. The results indicate that different potassium currents are involved in the repolarization of the narrow and wide action potentials in cat motor cortex. A novel tetraethylammonium-sensitive transient outward current and a 4-aminopyridine-sensitive outward current are responsible for the short duration and small amplitude of the narrow action potentials in the interneurons and some of the layer V pyramidal cells. These two currents are voltage-gated and Ca(2+)-independent. For the wide action potentials that characterize most pyramidal neurons, a Ca(2+)-independent tetraethylammonium-sensitive outward current and a Ca(2+)-activated potassium current are the main contributors to their repolarization.

Electrophysiological characteristics of hippocampal complex-spike cells and theta cells.

Stimulating electrodes were chronically implanted in the ventral hippocampal commissure and the entorhinal cortex or angular bundle of rats. Moveable metal microelectrodes which could be passed through the hippocampus were implanted. All hippocampal units were classified s complex-spike cells or theta cells on the basis of the form of their action potentials and their rates of firing in various behaviors. Field potentials and unit firing evoked from the stimulating electrodes were recorded during slow wave sleep. Complex-spike cells (1) could often be antidromically activated in CA3 (it was not attempted in CA1); (2) could only be induced to fire one or two action potentials in response to a single stimulus; (3) had action potentials at the same time as the local population-spike and, in condition-test studies, were depressed when the population-spike was depressed. (The population-spike is presumably the summed synchronous action potentials of pyramidal cells.) Theta cells: (1) were antidromically activated in only one out of 25 cases; (2) usually could fire long bursts of action potentials in response to a sufficiently intense single stimulus; (3) this firing occurred before, during, and after the local orthodromic population-spike. Most complex-spike cells in Ammon's horn must be pyramidal cells (projection cells), and vice versa. The case for theta cells is more difficult. Some are non-pyramidal cells with locally ramifying axons, but at least some are projection cells. The data is consistent with most of them being inhibitory interneurons, but this is not established.

Do enkephalins directly affect calcium-spikes in hippocampal pyramidal cells?

Although bath application of 10 −6 g/ml tetrodotoxin abolished the fast action potentials of pyramidal cells in hippocampal slices of rats, action potentials of lower amplitude and longer duration could still be evoked by intracellular current injection. FK 33–824 (an enkephalin analogue) had no effect on the threshold or shape of these presumed calcium-spikes. These data suggest that enkephalins, which induce bursting discharges in pyramidal cells, do not exert this action by a direct effect on inward calcium movement through the pyramidal cell membrane.