scholarly journals Contribution of near-threshold currents to intrinsic oscillatory activity in rat medial entorhinal cortex layer II stellate cells

2013 ◽  
Vol 109 (2) ◽  
pp. 445-463 ◽  
Author(s):  
Anne Boehlen ◽  
Christian Henneberger ◽  
Uwe Heinemann ◽  
Irina Erchova
Keyword(s):  
Entorhinal Cortex ◽  
Neuronal Excitability ◽  
Spatial Information ◽  
Sodium Current ◽  
Stellate Cells ◽  
Frequency Component ◽  
Oscillatory Activity ◽  
Potential Oscillations ◽  
Near Threshold

The temporal lobe is well known for its oscillatory activity associated with exploration, navigation, and learning. Intrinsic membrane potential oscillations (MPOs) and resonance of stellate cells (SCs) in layer II of the entorhinal cortex are thought to contribute to network oscillations and thereby to the encoding of spatial information. Generation of both MPOs and resonance relies on the expression of specific voltage-dependent ion currents such as the hyperpolarization-activated cation current ( IH), the persistent sodium current ( INaP), and the noninactivating muscarine-modulated potassium current ( IM). However, the differential contributions of these currents remain a matter of debate. We therefore examined how they modify neuronal excitability near threshold and generation of near-threshold MPOs and resonance in vitro. We found that resonance mainly relied on IH and was reduced by IH blockers and modulated by cAMP and an IM enhancer but that neither of the currents exhibited full control over MPOs in these cells. As previously reported, IH controlled a theta-frequency component of MPOs such that blockade of IH resulted in fewer regular oscillations that retained low-frequency components and high peak amplitude. However, pharmacological inhibition and augmentation of IM also affected MPO frequencies and amplitudes. In contrast to other cell types, inhibition of INaP did not result in suppression of MPOs but only in a moderation of their properties. We reproduced the experimentally observed effects in a single-compartment stochastic model of SCs, providing further insight into the interactions between different ionic conductances.

scholarly journals Development of Theta Rhythmicity in Entorhinal Stellate Cells of the Juvenile Rat

2008 ◽  
Vol 100 (6) ◽  
pp. 3144-3157 ◽  
Author(s):  
Brian G. Burton ◽  
Michael N. Economo ◽  
G. Jenny Lee ◽  
John A. White
Keyword(s):  
Sodium Current ◽  
Stellate Cells ◽  
Relative Importance ◽  
Persistent Sodium Current ◽  
Medial Entorhinal Cortex ◽  
Potential Oscillations ◽  
Hippocampal Network ◽  
Low Levels ◽  
Membrane Potential Oscillations

Mature stellate cells of the rat medial entorhinal cortex (EC), layer II, exhibit subthreshold membrane potential oscillations (MPOs) at theta frequencies (4–12 Hz) in vitro. We find that MPOs appear between postnatal days 14 (P14) and 18 (P18) but show little further change by day 28+ (P28–P32). To identify the factors responsible, we examined the electrical responses of developing stellate cells, paying attention to two currents thought necessary for mature oscillation: the h current Ih, which provides the slow rectification required for resonance; and a persistent sodium current INaP, which provides amplification of resonance. Responses to injected current revealed that P14 cells were often nonresonant with a relatively high resistance. Densities of Ih and INaP both rose by about 50% from P14 to P18. However, Ih levels fell to intermediate values by P28+. Given the nonrobust trend in Ih expression and a previously demonstrated potency of even low levels of Ih to sustain oscillation, we propose that resonance and MPOs are limited at P14 more by low levels of INaP than of Ih. The relative importance of INaP for the development of MPOs is supported by simulations of a conductance-based model, which also suggest that general shunt conductance may influence the precise age when MPOs appear. In addition to our physiological study, we analyzed spine densities at P14, P18, and P28+ and found a vigorous synaptogenesis across the whole period. Our data predict that functions that rely on theta rhythmicity in the hippocampal network are limited until at least P18.

scholarly journals Cholinergic Modulation of the Resonance Properties of Stellate Cells in Layer II of Medial Entorhinal Cortex

2010 ◽  
Vol 104 (1) ◽  
pp. 258-270 ◽  
Author(s):  
James G. Heys ◽  
Lisa M. Giocomo ◽  
Michael E. Hasselmo
Keyword(s):  
Patch Clamp ◽  
Resonance Frequency ◽  
Entorhinal Cortex ◽  
Stellate Cells ◽  
Cholinergic Modulation ◽  
Medial Entorhinal Cortex ◽  
Whole Cell ◽  
Whole Cell Patch Clamp ◽  
Resonance Properties

In vitro whole cell patch-clamp recordings of stellate cells in layer II of medial entorhinal cortex show a subthreshold membrane potential resonance in response to a sinusoidal current injection of varying frequency. Physiological recordings from awake behaving animals show that neurons in layer II medial entorhinal cortex, termed “grid cells,” fire in a spatially selective manner such that each cell's multiple firing fields form a hexagonal grid. Both the spatial periodicity of the grid fields and the resonance frequency change systematically in neurons along the dorsal to ventral axis of medial entorhinal cortex. Previous work has also shown that grid field spacing and acetylcholine levels change as a function of the novelty to a particular environment. Using in vitro whole cell patch-clamp recordings, our study shows that both resonance frequency and resonance strength vary as a function of cholinergic modulation. Furthermore, our data suggest that these changes in resonance properties are mediated through modulation of h-current and m-current.

Carbachol Induces Fast Oscillations in the Medial but not in the Lateral Entorhinal Cortex of the Isolated Guinea Pig Brain

1999 ◽  
Vol 82 (5) ◽  
pp. 2441-2450 ◽  
Author(s):  
Solange van der Linden ◽  
Ferruccio Panzica ◽  
Marco de Curtis
Keyword(s):  
Guinea Pig ◽  
Entorhinal Cortex ◽  
Gamma Oscillations ◽  
Gamma Activity ◽  
Oscillatory Activity ◽  
Medial Entorhinal Cortex ◽  
Arterial Perfusion ◽  
Fast Oscillations ◽  
Guinea Pig Brain

Fast oscillations at 25–80 Hz (gamma activity) have been proposed to play a role in attention-related mechanisms and synaptic plasticity in cortical structures. Recently, it has been demonstrated that the preservation of the entorhinal cortex is necessary to maintain gamma oscillations in the hippocampus. Because gamma activity can be reproduced in vitro by cholinergic activation, this study examined the characteristics of gamma oscillations induced by arterial perfusion or local intracortical injections of carbachol in the entorhinal cortex of the in vitro isolated guinea pig brain preparation. Shortly after carbachol administration, fast oscillatory activity at 25.2–28.2 Hz was observed in the medial but not in the lateral entorhinal cortex. Such activity was transiently associated with oscillations in the theta range that showed a variable pattern of distribution in the entorhinal cortex. No oscillatory activity was observed when carbachol was injected in the lateral entorhinal cortex. Gamma activity in the medial entorhinal cortex showed a phase reversal at 200–400 μm, had maximal amplitude at 400–500 μm depth, and was abolished by arterial perfusion of atropine (5 μM). Local carbachol application in the medial entorhinal cortex induced gamma oscillations in the hippocampus, whereas no oscillations were observed in the amygdala and in the piriform, periamygdaloid, and perirhinal cortices ipsilateral and contralateral to the carbachol injection. Hippocampal oscillations had higher frequency than the gamma activity recorded in the entorhinal cortex, suggesting the presence of independent generators in the two structures. The selective ability of the medial but not the lateral entorhinal cortex to generate gamma activity in response to cholinergic activation suggests a differential mode of signal processing in entorhinal cortex subregions.

scholarly journals KCC2 antagonism increases neuronal network excitability but disrupts ictogenesis in vitro

2019 ◽  
Vol 122 (3) ◽  
pp. 1163-1173 ◽  
Author(s):  
Li-Yuan Chen ◽  
Maxime Lévesque ◽  
Massimo Avoli
Keyword(s):  
Potassium Chloride ◽  
Entorhinal Cortex ◽  
Single Unit ◽  
Neuronal Excitability ◽  
Cell Activity ◽  
Principal Cell ◽  
Cell Firing ◽  
Interictal Discharges ◽  
Tetrode Recordings

The potassium-chloride cotransporter 2 (KCC2) plays a role in epileptiform synchronization, but it remains unclear how it influences such a process. Here, we used tetrode recordings in the in vitro rat entorhinal cortex (EC) to analyze the effects of the KCC2 antagonist VU0463271 on 4-aminopyridine (4AP)-induced ictal and interictal activity. During 4AP application, ictal events were associated with significant increases in interneurons and principal cells activities. VU0463271 application transformed ictal discharges to shorter ictal-like events that were not accompanied by significant increases in interneuron or principal cell firing. Interictal events persisted during VU0463271 application at an accelerated frequency of occurrence with significant increases in interneuron and principal cell activity. Further analysis revealed that interneuron and principal cell firing rate during 4AP-induced interictal events were increased after VU0463271 application without changes in synchronicity. Overall, our results demonstrate that in the EC, KCC2 antagonism enhances both interneuron and principal cell excitability, while paradoxically decreasing the ability of neuronal networks to generate structured ictal events. NEW & NOTEWORTHY We are the first to use tetrode recordings in the entorhinal cortex to demonstrate that antagonizing potassium-chloride cotransporter 2 (KCC2) function abolishes ictal discharges and the associated, dynamic changes in single-unit firing in the in vitro 4-aminopyrine model of epileptiform synchronization. Interictal discharges were, however, shorter and more frequent during KCC2 antagonism, while the associated single-unit activity increased, suggesting augmented neuronal excitability. Our findings highlight the complex role of KCC2 in disease pathology.

Differential electroresponsiveness of stellate and pyramidal-like cells of medial entorhinal cortex layer II

1993 ◽  
Vol 70 (1) ◽  
pp. 128-143 ◽  
Author(s):  
A. Alonso ◽  
R. Klink
Keyword(s):  
Membrane Potential ◽  
Entorhinal Cortex ◽  
Morphological Characteristics ◽  
Oscillatory Activity ◽  
Inward Rectification ◽  
Projection Neurons ◽  
Medial Entorhinal Cortex ◽  
Mean Frequency ◽  
Subthreshold Oscillations

1. The electroresponsive properties of neurons from layer II of the rat medial entorhinal cortex (MEC) were studied by intracellular recording under current clamp in an in vitro brain slice preparation. From a total of 184 cells that fulfilled our criteria for recording stability, two groups of projection neurons were distinguished on the basis of their intrinsic biophysical properties and morphological characteristics (demonstrated by intracellular biocytin injection; n = 34). 2. Stellate cells (SCs) were the most abundant (69%). They were highly electroresponsive, and minimal changes (1-3 mV) of membrane potential generated an active response. Subthreshold depolarizing or hyperpolarizing current pulse injection always caused the membrane potential to attain an early peak and then sag to a lower level. Depolarization-induced "sags" were larger and determined early firing in all cells. The voltage-current relationship of SCs was markedly non-linear, demonstrating robust inward rectification in the hyperpolarizing and depolarizing range. 3. SCs generated persistent rhythmic subthreshold voltage oscillations on DC depolarization positive to -60 mV. The mean frequency of the oscillations was 8.6 Hz (theta range) at a membrane potential of approximately -55 mV, at which level occasional single spiking also occurred. At slightly more positive potentials, a striking 1- to 3-Hz repetitive bursting pattern emerged. This consisted of nonadapting trains of spikes ("clusters") interspersed with subthreshold oscillations that had a mean frequency of 21.7 Hz (beta range). 4. Nonstellate cells (39%; mostly pyramidal-like) displayed time-dependent inward rectification that was less pronounced than that of SCs, and minimal depolarization-induced sags. On threshold depolarization, firing was always preceded by a slowly rising ramp depolarization and thus occurred with a long delay. Inward rectification in the depolarizing range was very pronounced. However, non-SCs did not generate persistent rhythmic subthreshold oscillatory activity or spike clusters. 5. Of the electrophysiological parameters quantified, spike threshold, spike duration, depolarizing afterpotential amplitude and apparent membrane time constant demonstrated statistically significant differences between SCs and non-SCs. 6. The repetitive hiring properties in response to square current pulses of short duration (< 500 ms) were also different between SCs and non-SCs. First, most SCs displayed a bilinear frequency-current (f-I) relationship for only the first interspike interval, whereas most non-SCs displayed a bilinear relationship for all intervals. Second, SCs had a much steeper primary f-I slope for early intervals than non-SCs. Finally, SCs displayed more pronounced and faster spike frequency adaptation than non-SCs.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Monoterpenoid Terpinen-4-ol Exhibits Anticonvulsant Activity in Behavioural and Electrophysiological Studies

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Franklin F. F. Nóbrega ◽  
Mirian G. S. S. Salvadori ◽  
Cintia J. Masson ◽  
Carlos F. Mello ◽  
Tiago S. Nascimento ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Sodium Current ◽  
Anticonvulsant Effect ◽  
Aromatic Plants ◽  
Gabaergic Neurotransmission ◽  
Benzodiazepine Binding ◽  
Voltage Dependent ◽  
Electrophysiological Studies ◽  
Anticonvulsant Effects

Terpinen-4-ol (4TRP) is a monoterpenoid alcoholic component of essential oils obtained from several aromatic plants. We investigated the psychopharmacological and electrophysiological activities of 4TRP in male Swiss mice and Wistar rats. 4TRP was administered intraperitoneally (i.p.) at doses of 25 to 200 mg/kg and intracerebroventricularly (i.c.v.) at concentrations of 10, 20, and 40 ng/2 μL. For in vitro experiments, 4TRP concentrations were 0.1 mM and 1.0 mM. 4TRP (i.p.) inhibited pentylenetetrazol- (PTZ-) induced seizures, indicating anticonvulsant effects. Electroencephalographic recordings showed that 4TRP (i.c.v.) protected against PTZ-induced seizures, corroborating the behavioural results. To determine whether 4TRP exerts anticonvulsant effects via regulation of GABAergic neurotransmission, we measured convulsions induced by 3-mercapto-propionic acid (3-MP). The obtained results showed involvement of the GABAergic system in the anticonvulsant action exerted by 4TRP, but flumazenil, a selective antagonist of the benzodiazepine site of theGABAAreceptor, did not reverse the anticonvulsant effect, demonstrating that 4TRP does not bind to the benzodiazepine-binding site. Furthermore, 4TRP decreased the sodium current through voltage-dependent sodium channels, and thus its anticonvulsant effect may be related to changes in neuronal excitability because of modulation of these channels.

scholarly journals Autoactivity of A5 neurons: role of subthreshold oscillations and persistent Na+current

1997 ◽  
Vol 273 (5) ◽  
pp. H2280-H2289 ◽  
Author(s):  
Donghai Huangfu ◽  
Patrice G. Guyenet
Keyword(s):  
Membrane Potential ◽  
Discharge Rate ◽  
Input Resistance ◽  
Frequency Component ◽  
Inward Rectification ◽  
Intrinsic Properties ◽  
Potential Oscillations ◽  
Subthreshold Oscillations

A5 noradrenergic neurons play a key role in autonomic regulation, nociception, and respiration. The purpose of the present experiments was to characterize some of the intrinsic properties of A5 cells in vitro. Whole cell recordings were obtained from 85 spinally projecting neurons of the ventrolateral pons of neonate rats. Immunohistochemistry showed that 60% of the ventrolateral pontine cells were noradrenergic. Eighty percent of A5 neurons were spontaneously active (0.1–5.5 spikes/s). Their discharge rate was unchanged by a mixture of synaptic blockers that eliminated postsynaptic potentials (PSPs). The nonnoradrenergic cells could not be distinguished from A5 cells on the basis of discharge rate, action potential duration, inward rectification, input resistance, or accommodation. A5 cells displayed subthreshold irregular oscillations of the membrane potential (main frequency component 0.5–2 Hz). These oscillations were unchanged in the presence of low external Ca2+-high Mg2+ and were very reduced by hyperpolarizing the cells below −65 mV. The oscillations were partially attenuated by 1 μM tetrodotoxin (TTX) and were eliminated by reducing external Na+ (27 mM). Stepping the membrane potential from −65 to −50 mV for 200 ms revealed the presence of a transient and a persistent inward current that were both blocked by 0.1 μM TTX or by extracellular Na+ reduction. In conclusion, most A5 neurons are spontaneously active in vitro. They display irregular subthreshold membrane potential oscillations generated by voltage-activated conductances that include a persistent TTX-sensitive Na+ current. Most of the activity of A5 cells appears due to intrinsic properties rather than to synaptic inputs.

Slow Periodic Events and Their Transition to Gamma Oscillations in the Entorhinal Cortex of the Isolated Guinea Pig Brain

2003 ◽  
Vol 90 (1) ◽  
pp. 39-46 ◽  
Author(s):  
Clayton T. Dickson ◽  
Gerardo Biella ◽  
Marco de Curtis
Keyword(s):  
Membrane Potential ◽  
Guinea Pig ◽  
Entorhinal Cortex ◽  
Gamma Oscillations ◽  
Oscillatory Activity ◽  
Periodic Field ◽  
Slow Potential ◽  
Pig Brain ◽  
Guinea Pig Brain

Slow (<1 Hz) periodic activity is a distinctive discharge pattern observed in different cortical and sub-cortical structures during sleep and anesthesia. By performing field and cellular recordings, we demonstrated that slow periodic events (0.02–0.4 Hz) are spontaneously generated in the entorhinal cortex of the in vitro isolated whole brain of the guinea pig. These events were characterized by gradually developing runs of low-amplitude (50–300 μV), high-frequency (25–70 Hz) oscillations superimposed on a slow potential that lasted 1–3 s. Both slow and fast components showed a phase reversal in the superficial layers. In layer II-III entorhinal neurons, the slow periodic events correlated to a slowly developing depolarizing envelope capped by subthreshold membrane potential oscillations and action potential discharge. Slow periodic field events propagated tangentially across the entorhinal cortex and could be triggered by stimulation of superficial associative fibers, suggesting that they were generated by and propagated via network interactions in the superficial layers. Slow periodic events were reversibly abolished by muscarinic excitation elicited by carbachol (50 μM) that promoted intracellular membrane potential depolarization associated with continuous fast oscillatory activity in the gamma frequency range. These results suggest that, as proposed in vivo, activity changes in the entorhinal cortex of the in vitro isolated guinea-pig brain reflect different activation states that are under cholinergic control.

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