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ABSTRACT: Neuronal impedance characterizes the magnitude and timing of the subthreshold response of a neuron to oscillatory input at a given frequency. It is known to be influenced by both the morphology of the neuron and the presence of voltage-gated conductances in the cell membrane. Most existing theoretical accounts of neuronal impedance considered the effects of voltage-gated conductances but neglected the spatial extent of the cell, while others examined spatially extended dendrites with a passive or spatially uniform quasi-active membrane. We derived an explicit mathematical expression for the somatic input impedance of a model neuron consisting of a somatic compartment coupled to an infinite dendritic cable which contained voltage-gated conductances, in the more general case of non-uniform dendritic membrane potential. The validity and generality of this model was verified through computer simulations of various model neurons. The analytical model was then applied to the analysis of experimental data from real CA1 pyramidal neurons. The model confirmed that the biophysical properties and predominantly dendritic localization of the hyperpolarization-activated cation current I (h) were important determinants of the impedance profile, but also predicted a significant contribution from a depolarization-activated fast inward current. Our calculations also implicated the interaction of I (h) with amplifying currents as the main factor governing the shape of the impedance-frequency profile in two types of hippocampal interneuron. Our results provide not only a theoretical advance in our understanding of the frequency-dependent behavior of nerve cells, but also a practical tool for the identification of candidate mechanisms that determine neuronal response properties.
Journal of Computational Neuroscience 02/2012; 33(2):257-84. · 2.51 Impact Factor
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ABSTRACT: Traditionally, Echinacea preparations are used as antiinflammatory agents and immune-enhancers. In addition to these effects, their anxiolytic potency has been recognized recently in laboratory tests. Our aim in this study was to uncover the potential effects of an Echinacea preparation on neuronal operations in the hippocampus, a brain region that is involved in anxiety and anxiety-related behaviors. Using in vitro electrophysiological techniques, we observed that excitatory synaptic transmission in hippocampal slices was significantly suppressed by an Echinacea extract found to be effective in anxiety tests. In contrast, no change in inhibitory synaptic transmission could be detected upon application of this extract. In addition, our experiments revealed that at low concentration the Echinacea extract reduced the spiking activity of CA1 pyramidal cells, while at high concentration increased it. This latter observation was parallel to the reduction in the magnitude of the h-current-mediated voltage responses in pyramidal cells. At any concentrations, the passive membrane properties of CA1 pyramidal cells were found to be unaltered by the Echinacea extract. In summary, the Echinacea extract can significantly regulate excitatory, but not inhibitory, synaptic transmission in the hippocampus, and this action might be involved in its anxiolytic effects observed in behaviour tests.
Phytotherapy Research 06/2011; 26(3):354-62. · 2.09 Impact Factor
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ABSTRACT: The intrinsic properties of distinct types of neuron play important roles in cortical network dynamics. One crucial determinant of neuronal behaviour is the cell's response to rhythmic subthreshold input, characterised by the input impedance, which can be determined by measuring the amplitude and phase of the membrane potential response to sinusoidal currents as a function of input frequency. In this study, we determined the impedance profiles of anatomically identified neurons in the CA1 region of the rat hippocampus (pyramidal cells as well as interneurons located in the stratum oriens, including OLM cells, fast-spiking perisomatic region-targeting interneurons and cells with axonal arbour in strata oriens and radiatum). The basic features of the impedance profiles, as well as the passive membrane characteristics and the properties of the sag in the voltage response to negative current steps, were cell-type specific. With the exception of fast-spiking interneurons, all cell types showed subthreshold resonance, albeit with distinct features. The HCN channel blocker ZD7288 (10 microM) eliminated the resonance and changed the shape of the impedance curves, indicating the involvement of the hyperpolarization-activated cation current I(h). Whole-cell voltage-clamp recordings uncovered differences in the voltage-dependent activation and kinetics of I(h) between different cell types. Biophysical modelling demonstrated that the cell-type specificity of the impedance profiles can be largely explained by the properties of I(h) in combination with the passive membrane characteristics. We conclude that differences in I(h) and passive membrane properties result in a cell-type-specific response to inputs at given frequencies, and may explain, at least in part, the differential involvement of distinct types of neuron in various network oscillations.
The Journal of Physiology 06/2010; 588(Pt 12):2109-32. · 4.72 Impact Factor
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ABSTRACT: Studies in brain slices have provided a wealth of data on the basic features of neurons and synapses. In the intact brain, these properties may be strongly influenced by ongoing network activity. Although physiologically realistic patterns of network activity have been successfully induced in brain slices maintained in interface-type recording chambers, they have been harder to obtain in submerged-type chambers, which offer significant experimental advantages, including fast exchange of pharmacological agents, visually guided patch-clamp recordings, and imaging techniques. Here, we investigated conditions for the emergence of network oscillations in submerged slices prepared from the hippocampus of rats and mice. We found that the local oxygen level is critical for generation and propagation of both spontaneously occurring sharp wave-ripple oscillations and cholinergically induced fast oscillations. We suggest three ways to improve the oxygen supply to slices under submerged conditions: (i) optimizing chamber design for laminar flow of superfusion fluid; (ii) increasing the flow rate of superfusion fluid; and (iii) superfusing both surfaces of the slice. These improvements to the recording conditions enable detailed studies of neurons under more realistic conditions of network activity, which are essential for a better understanding of neuronal network operation.
European Journal of Neuroscience 02/2009; 29(2):319-27. · 3.63 Impact Factor
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ABSTRACT: The medial septum (MS) is an indispensable component of the subcortical network which synchronizes the hippocampus at theta frequency during specific stages of information processing. GABAergic neurons exhibiting highly regular firing coupled to the hippocampal theta rhythm are thought to form the core of the MS rhythm-generating network. In recent studies the hyperpolarization-activated, cyclic nucleotide-gated non-selective cation (HCN) channel was shown to participate in theta synchronization of the medial septum. Here, we tested the hypothesis that HCN channel expression correlates with theta modulated firing behaviour of MS neurons by a combined anatomical and electrophysiological approach. HCN-expressing neurons represented a subpopulation of GABAergic cells in the MS partly overlapping with parvalbumin (PV)-containing neurons. Rhythmic firing in the theta frequency range was characteristic of all HCN-expressing neurons. In contrast, only a minority of HCN-negative cells displayed theta related activity. All HCN cells had tight phase coupling to hippocampal theta waves. As a group, PV-expressing HCN neurons had a marked bimodal phase distribution, whereas PV-immunonegative HCN neurons did not show group-level phase preference despite significant individual phase coupling. Microiontophoretic blockade of HCN channels resulted in the reduction of discharge frequency, but theta rhythmic firing was perturbed only in a few cases. Our data imply that HCN-expressing GABAergic neurons provide rhythmic drive in all phases of the hippocampal theta activity. In most MS theta cells rhythm genesis is apparently determined by interactions at the level of the network rather than by the pacemaking property of HCN channels alone.
The Journal of Physiology 07/2008; 586(16):3893-915. · 4.72 Impact Factor
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ABSTRACT: A kérgi neuronhálózatokban megfigyelt gamma (30-100 Hz) oszcillációk alapvető szerepet játszanak olyan kognitív folyamatokban, mint pl. a szenzoros információfeldolgozás. Funkciójuk megértéséhez ismernünk kell a neuronhálózatokat alkotó serkentő és gátlósejtek viselkedését ill. szerepét az oszcillációk kialakításában. Pályázatunk célja a hippokampális ideghálózatok szinkronizált működését kialakító sejtszintű mechanizmusok felderítése volt. In vitro farmakológiailag indukált oszcillációk során vizualizált patch-clamp méréstechnika segítségével megállapítottuk, hogy a hippokampusz CA3 régiójában keletkező gamma oszcillációkat a gyorsan tüzelő kosársejtek és a piramissejtek időben összehangolt kisülése generálja szinaptikus visszacsatolás révén. A hippokampusz CA1 régiójába a gamma oszcilláció előrecsatoló gátlással terjed át a CA3 régióból. Mindkét régióban a gátlósejtek oszcillációhoz viszonyított fáziskapcsolt tüzelését a rájuk érkező szinaptikus serkentés, míg a piramissejtek kisülését a szinaptikus gátlás határozta meg. Kifejlesztettünk egy szabadalmi bejelentéssel védett szeletkamrát in vitro mérésekhez, melyben az agyszeletek oxigénellátása megközelíti az in vivo körülményeket. Az eredményeinknek klinikai vonatkozása is elképzelhető, hiszen az epilepszia tünetcsoportban tapasztalt hiperszinkonitás kialakulásában is kulcsfontosságú szerepet játszhatnak a gyorsan tüzelő kosársejtek, amely gátlósejtek működésének célzott szabályozása egy potenciális gyógyszercélpont lehet. | Cortical network oscillations at gamma (30-100 Hz) frequencies were suggested to be linked to several cognitive tasks including sensory processing. To understand the role of oscillations in neuronal operation, the behavior and the function of different neuronal types during oscillatory activities need to be revealed. The aim of our project was to uncover the basic cellular mechanisms generating synchronous network activities in hippocampal neuronal circuitries. The combination of visualized patch-clamp recordings with pharmacologically-induced in vitro oscillations allowed us to determine that in CA3 hippocampal region the precisely timed discharge of fast spiking basket cells and pyramidal cells could generate the gamma oscillations via a synaptic feed-back loop. The gamma oscillation emerged intrinsically in CA3 propagates to CA1 via feed-forward inhibition. In both regions, the phase-coupled firing of inhibitory cells was controlled by synaptic excitation, whereas the discharge of pyramidal cells was primarily determined by synaptic inhibition. For in vitro recordings we developed a new type of slice chamber protected by a patent, where the oxygen supply of brain slices approaches the in vivo circumstances. Our results also have clinical relevance implying the pivotal role of fast spiking basket cells in hypersynchrony during epileptic discharges, therefore the modulation of the fast spiking basket cell operation might be a novel target for drug development.
