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)

Ionic mechanisms for the subthreshold oscillations and differential electroresponsiveness of medial entorhinal cortex layer II neurons

1993 ◽  
Vol 70 (1) ◽  
pp. 144-157 ◽  
Author(s):  
R. Klink ◽  
A. Alonso
Keyword(s):  
Membrane Potential ◽  
Entorhinal Cortex ◽  
Inward Rectification ◽  
Voltage Level ◽  
Medial Entorhinal Cortex ◽  
Potential Oscillations ◽  
Subthreshold Oscillations ◽  
Outward Rectification ◽  
Ionic Mechanisms ◽  
Membrane Potential Oscillations

1. Layer II of the medial entorhinal cortex is composed of two electrophysiologically and morphologically distinct types of projection neurons: stellate cells (SCs), which are distinguished by rhythmic subthreshold oscillatory activity, and non-SCs. The ionic mechanisms underlying their differential electroresponsiveness, particularly in the subthreshold range of membrane potentials, were investigated in an "in vitro" slice preparation. 2. In both SCs and non-SCs, the apparent membrane input resistance was markedly voltage dependent, respectively decreasing or increasing at hyperpolarized or subthreshold depolarized potential levels. Thus the neurons displayed inward rectification in the hyperpolarizing and depolarizing range. 3. In the depolarizing range, inward rectification was blocked by tetrodotoxin (TTX, 1 microM) in both types of neurons and thus shown to depend on the presence of a persistent low-threshold Na+ conductance (gNap). However, in the presence of TTX, pronounced outward rectification became manifest in the subthreshold depolarizing range of membrane potentials (positive to -60 mV) in the SCs but not in the non-SCs. 4. The rhythmic subthreshold membrane potential oscillations that were present only in the SCs were abolished by TTX and not by Ca2+ conductance block with Cd2+ or Co2+. Subthreshold oscillations thus rely on the activation of voltage-gated Na+, and not Ca2+, conductances. The Ca2+ conductance block also had no effect on the subthreshold outward rectification. 5. Prominent time-dependent inward rectification in the hyperpolarizing range in the SCs persisted after Na(+)- and Ca2+ conductance block. This rectification was not affected by Ba2+ (1 mM), but was blocked by Cs+ (1-4 mM). Therefore, it is most probably generated by a hyperpolarization-activated cationic current (Q-like current). However, the Q-like current appears to play no major role in the generation of subthreshold rhythmic membrane potential oscillations, because these persisted in the presence of Cs+. 6. On the other hand, in the SCs, the fast, sustained, outward rectification that strongly developed (after Na+ conductance block) at the oscillatory voltage level was not affected by Cs+ but was blocked by Ba2+ (1 mM). Barium was also effective in blocking the subthreshold membrane potential oscillations. 7. In the non-SCs, which do not generate subthreshold rhythmic membrane potential oscillations or manifest subthreshold outward rectification in TTX, Ca2+ conductance block abolished spike repolarization and caused the development of long-lasting Na(+)-dependent plateau potentials at a high suprathreshold voltage level. At this level, where prominent delayed rectification is present, the Na+ plateaus sustained rhythmic membrane potential oscillations.(ABSTRACT TRUNCATED AT 400 WORDS)

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 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.

Properties and Role of I h in the Pacing of Subthreshold Oscillations in Entorhinal Cortex Layer II Neurons

2000 ◽  
Vol 83 (5) ◽  
pp. 2562-2579 ◽  
Author(s):  
Clayton T. Dickson ◽  
Jacopo Magistretti ◽  
Mark H. Shalinsky ◽  
Erik Fransén ◽  
Michael E. Hasselmo ◽  
...  
Keyword(s):  
Entorhinal Cortex ◽  
Hippocampal Formation ◽  
Reversal Potential ◽  
Perforant Path ◽  
Oscillatory Activity ◽  
Inward Rectification ◽  
Oscillatory Process ◽  
Biophysical Parameters ◽  
Inward Current ◽  
Subthreshold Oscillations

Various subsets of brain neurons express a hyperpolarization-activated inward current ( I h) that has been shown to be instrumental in pacing oscillatory activity at both a single-cell and a network level. A characteristic feature of the stellate cells (SCs) of entorhinal cortex (EC) layer II, those neurons giving rise to the main component of the perforant path input to the hippocampal formation, is their ability to generate persistent, Na+-dependent rhythmic subthreshold membrane potential oscillations, which are thought to be instrumental in implementing theta rhythmicity in the entorhinal-hippocampal network. The SCs also display a robust time-dependent inward rectification in the hyperpolarizing direction that may contribute to the generation of these oscillations. We performed whole cell recordings of SCs in in vitro slices to investigate the specific biophysical and pharmacological properties of the current underlying this inward rectification and to clarify its potential role in the genesis of the subthreshold oscillations. In voltage-clamp conditions, hyperpolarizing voltage steps evoked a slow, noninactivating inward current, which also deactivated slowly on depolarization. This current was identified as I h because it was resistant to extracellular Ba2+, sensitive to Cs+, completely and selectively abolished by ZD7288, and carried by both Na+and K+ ions. I h in the SCs had an activation threshold and reversal potential at approximately −45 and −20 mV, respectively. Its half-activation voltage was −77 mV. Importantly, bath perfusion with ZD7288, but not Ba2+, gradually and completely abolished the subthreshold oscillations, thus directly implicating I h in their generation. Using experimentally derived biophysical parameters for I h and the low-threshold persistent Na+ current ( I NaP) present in the SCs, a simplified model of these neurons was constructed and their subthreshold electroresponsiveness simulated. This indicated that the interplay between I NaP and I h can sustain persistent subthreshold oscillations in SCs. I NaP and I h operate in a “push-pull” fashion where the delay in the activation/deactivation of I h gives rise to the oscillatory process.

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.

Synaptic and intrinsic responses of medical entorhinal cortical cells in normal and magnesium-free medium in vitro

1988 ◽  
Vol 59 (5) ◽  
pp. 1476-1496 ◽  
Author(s):  
R. S. Jones ◽  
U. Heinemann
Keyword(s):  
Entorhinal Cortex ◽  
Action Potentials ◽  
Membrane Conductance ◽  
Nmda Receptor Antagonist ◽  
Field Potentials ◽  
Cortical Cells ◽  
Medial Entorhinal Cortex ◽  
Membrane Hyperpolarization

1. Extracellular recordings were made from slices of hippocampus plus parahippocampal regions maintained in vitro. Field potentials, recorded in the entorhinal cortex after stimulation in the subiculum, resembled those observed in vivo. 2. Washout of magnesium from the slices resulted in paroxysmal events which resembled those occurring during sustained seizures in vivo. These events were greatest in amplitude and duration in layers IV/V of the medial entorhinal cortex and could occur both spontaneously and in response to subicular stimulation. Spontaneous seizure-like events were not prevented by severing the connections between the hippocampus and entorhinal cortex, but much smaller and shorter events occurring in the dentate gyrus were stopped by this manipulation. Both spontaneous and evoked paroxysmal events were blocked by perfusion with the N-methyl-D-aspartate (NMDA) receptor antagonist, DL-2-amino-5-phosphonovalerate (2-AP5). 3. Neurons in layers IV/V were characterized by intracellular recording. Injection of depolarizing current in most cells evoked a train of nondecrementing action potentials with only weak spike frequency accommodation and little or no posttrain after hyperpolarization. 4. A small number of cells displayed burst response when depolarized by positive current. The burst consisted of a slow depolarization with superimposed action potentials which decreased in amplitude and increased in duration during the discharge. The burst was terminated by a strong after hyperpolarization and thereafter, during prolonged current pulses a train of nondecrementing spikes occurred. The burst response remained if the cell was held at hyperpolarized levels but was inactivated by holding the cell at a depolarized level. 5. Depolarizing synaptic potentials could be evoked by stimulation in the subiculum. A delayed and prolonged depolarization clearly decremented with membrane hyperpolarization and, occasionally, increased with depolarization. 6. Washout of magnesium from the slices resulted in an enhancement of the late depolarization and a reversal of its voltage dependence. Eventually a single shock to the subiculum evoked a large all-or-none paroxysmal depolarization associated with a massive increase in membrane conductance. Similar events occurred spontaneously in all cells tested. The paroxysmal depolarizations, both spontaneous and evoked, were rapidly blocked by 2-AP5. 7. It is concluded that medial entorhinal cortical cells possess several intrinsic and synaptic properties which confer an extreme susceptibility to generation of sustained seizure activity.(ABSTRACT TRUNCATED AT 400 WORDS)

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