Muscarinic Modulation of the Oscillatory and Repetitive Firing Properties of Entorhinal Cortex Layer II Neurons

1997 ◽  
Vol 77 (4) ◽  
pp. 1813-1828 ◽  
Author(s):  
Ruby Klink ◽  
Angel Alonso
Keyword(s):  
Entorhinal Cortex ◽  
Repetitive Firing ◽  
Potential Oscillations ◽  
Cyclic Monophosphate ◽  
Oscillatory Dynamics ◽  
Adenosine Cyclic Monophosphate ◽  
Voltage Dependent ◽  
Firing Properties ◽  
Muscarinic Modulation ◽  
Membrane Potential Oscillations

Klink, Ruby and Angel Alonso. Muscarinic modulation of the oscillatory and repetitive firing properties of entorhinal cortex layer II neurons. J. Neurophysiol. 77: 1813–1828, 1997. Neurons in layer II of the entorhinal cortex (EC) are key elements in the temporal lobe memory system because they integrate and transfer into the hippocampal formation convergent sensory input from the entire cortical mantle. EC layer II also receives a profuse cholinergic innervation from the basal forebrain that promotes oscillatory dynamics in the EC network and may also implement memory function. To understand the cellular basis of cholinergic actions in EC, we investigated by intracellular recording in an in vitro rat brain slice preparation the muscarinic modulation of the electroresponsive properties of the two distinct classes of medial EC layer II projection neurons, the stellate cells (SCs) and non-SCs. In both SCs and non-SCs, muscarinic receptor activation with carbachol (CCh, 10–50 μM) caused atropine-sensitive (300 nM) membrane depolarization. In SCs, the CCh-induced membrane depolarization was associated with subthreshold membrane potential oscillations and “spike cluster” discharge, which are typically expressed by these cells on depolarization. CCh, however, caused a decrease of the dominant frequency of the membrane potential oscillations from 9.2 ± 1.1 (SD) Hz to 6.3 ± 1.1 Hz, as well as a decrease of the intracluster firing frequency from 18.1 ± 1.7 Hz to 13.6 ± 1.3 Hz. In addition, spike cluster discharge was less robust, and the cells tended to shift into tonic firing during CCh. In contrast to SCs, in non-SCs, CCh drastically affected firing behavior by promoting the development of voltage-dependent, long-duration (1–5 s) slow bursts of action potentials that could repeat rhythmically at slow frequencies (0.2–0.5 Hz). Concomitantly, the slow afterhyperpolarization (sAHP) was replaced by long-lasting plateau postdepolarizations. In both SCs and non-SCs, CCh also produced conspicuous changes on the action potential waveform and its afterpotentials. Notably, CCh significantly decreased spike amplitude and rate of rise, which suggests muscarinic modulation of a voltage-dependent Na+ conductance. Finally, we also observed that whereas CCh abolished the sAHP in both SCs and non-SCs, the membrane-permeant analogues of adenosine 3′,5′-cyclic monophosphate, 8-(4-chlorophenylthio)-adenosine-cyclic monophosphate and 8-bromo-adenosine-cyclic-monophosphate, abolished the sAHP in SCs but not in non-SCs. The data demonstrate that cholinergic modulation further differentiates the intrinsic electroresponsiveness of SCs and non-SCs, and add support to the presence of two parallel processing systems in medial EC layer II that could thereby differentially influence their hippocampal targets. The results also indicate an important role for the cholinergic system in tuning the oscillatory dynamics of entorhinal neurons.

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)

scholarly journals Conductances Mediating Intrinsic Theta-Frequency Membrane Potential Oscillations in Layer II Parasubicular Neurons

2008 ◽  
Vol 100 (5) ◽  
pp. 2746-2756 ◽  
Author(s):  
Stephen D. Glasgow ◽  
C. Andrew Chapman
Keyword(s):  
Membrane Potential ◽  
Network Activity ◽  
Potential Oscillations ◽  
Cationic Current ◽  
Artificial Cerebrospinal Fluid ◽  
Theta Frequency ◽  
Ionic Conductances ◽  
Voltage Dependent ◽  
Cell Current ◽  
Membrane Potential Oscillations

Ionic conductances that generate membrane potential oscillations in neurons of layer II of the parasubiculum were studied using whole cell current-clamp recordings in horizontal slices from the rat brain. Blockade of ionotropic glutamate and GABA synaptic transmission did not reduce the power of the oscillations, indicating that oscillations are not dependent on synaptic inputs. Oscillations were eliminated when cells were hyperpolarized 6–10 mV below spike threshold, indicating that they are mediated by voltage-dependent conductances. Application of TTX completely eliminated oscillations, suggesting that Na+ currents are required for the generation of the oscillations. Oscillations were not reduced by blocking Ca2+ currents with Cd2+ or Ca2+-free artificial cerebrospinal fluid, or by blocking K+ conductances with either 50 μM or 5 mM 4-aminopyridine (4-AP), 30 mM tetraethylammonium (TEA), or Ba2+(1–2 mM). Oscillations also persisted during blockade of the muscarinic-dependent K+ current, IM, using the selective antagonist XE-991 (10 μM). However, oscillations were significantly attenuated by blocking the hyperpolarization-activated cationic current Ih with Cs+ and were almost completely blocked by the more potent Ih blocker ZD7288 (100 μM). Intrinsic membrane potential oscillations in neurons of layer II of the parasubiculum are therefore likely driven by an interaction between an inward persistent Na+ current and time-dependent deactivation of Ih. These voltage-dependent conductances provide a mechanism for the generation of membrane potential oscillations that can help support rhythmic network activity within the parasubiculum during theta-related behaviors.

Subthreshold membrane potential oscillations in neurons of deep layers of the entorhinal cortex

Neuroscience ◽  
1998 ◽  
Vol 85 (4) ◽  
pp. 999-1004 ◽  
Author(s):  
D. Schmitz ◽  
T. Gloveli ◽  
J. Behr ◽  
T. Dugladze ◽  
U. Heinemann
Keyword(s):  
Membrane Potential ◽  
Entorhinal Cortex ◽  
Potential Oscillations ◽  
Deep Layers ◽  
Membrane Potential Oscillations

scholarly journals Intracellular QX-314 Causes Depression of Membrane Potential Oscillations in Lamprey Spinal Neurons During Fictive Locomotion

2002 ◽  
Vol 87 (6) ◽  
pp. 2676-2683 ◽  
Author(s):  
Guo-Yuan Hu ◽  
Zoltán Biró ◽  
Russell H. Hill ◽  
Sten Grillner
Keyword(s):  
Spinal Cord ◽  
Membrane Potential ◽  
Dendritic Tree ◽  
Cell Voltage ◽  
Fictive Locomotion ◽  
Spinal Neurons ◽  
Potential Oscillations ◽  
Short Pulses ◽  
Voltage Dependent ◽  
Membrane Potential Oscillations

Spinal neurons undergo large cyclic membrane potential oscillations during fictive locomotion in lamprey. It was investigated whether these oscillations were due only to synaptically driven excitatory and inhibitory potentials or if voltage-dependent inward conductances also contribute to the depolarizing phase by using N-(2,6-dimethylphenyl carbamoylmethyl)triethylammonium bromide (QX-314) administered intracellularly during fictive locomotion. QX-314 intracellularly blocks inactivating and persistent Na+ channels, and in some neurons, effects on certain other types of channels have been reported. To detail the effects of QX-314 on Na+ and Ca2+ channels, we used dissociated lamprey neurons recorded under whole cell voltage clamp. At low intracellular concentrations of QX-314 (0.2 mM), inactivating Na+ channels were blocked and no effects were exerted on Ca2+ channels (also at 0.5 mM). At 10 mM QX-314, there was, however a marked reduction of I Ca. In the isolated spinal cord of the lamprey, fictive locomotion was induced by superfusing the spinal cord with Ringer's solution containing N-methyl-d-aspartate (NMDA), while recording the locomotor activity from the ventral roots. Simultaneously, identified spinal neurons were recorded intracellularly, while infusing QX-314 from the microelectrode. Patch electrodes cannot be used in the intact spinal cord, and therefore “sharp” electrodes were used. The amplitude of the oscillations was consistently reduced by 20–25% in motoneurons ( P < 0.05) and unidentified spinal neurons ( P < 0.005). The onset of the effect started a few minutes after impalement and reached a stable level within 30 min. These effects thus show that QX-314 causes a reduction in the amplitude of membrane potential oscillations during fictive locomotion. We also investigated whether QX-314 could affect glutamate currents by applying short pulses of glutamate from an extracellular pipette. No changes were observed. We also found no evidence for a persistent Na+ current in dissociated neurons, but these cells have a much-reduced dendritic tree. The results indicate that there is an inward conductance, which is sensitive to QX-314, during membrane potential oscillations that “boosts” the synaptic drive during fictive locomotion. Taken together, the results suggest that inactivating Na+ channels contribute to this inward conductance although persistent Na+channels, if present on dendrites, could possibly also contribute to shaping the membrane potential oscillations.

scholarly journals Linking Cellular Mechanisms to Behavior: Entorhinal Persistent Spiking and Membrane Potential Oscillations May Underlie Path Integration, Grid Cell Firing, and Episodic Memory

2008 ◽  
Vol 2008 ◽  
pp. 1-12 ◽  
Author(s):  
Michael E. Hasselmo ◽  
Mark P. Brandon
Keyword(s):  
Membrane Potential ◽  
Episodic Memory ◽  
Entorhinal Cortex ◽  
Path Integration ◽  
Grid Cell ◽  
Physiological Data ◽  
Cellular Mechanisms ◽  
Potential Oscillations ◽  
Cell Firing ◽  
Membrane Potential Oscillations

The entorhinal cortex plays an important role in spatial memory and episodic memory functions. These functions may result from cellular mechanisms for integration of the afferent input to entorhinal cortex. This article reviews physiological data on persistent spiking and membrane potential oscillations in entorhinal cortex then presents models showing how both these cellular mechanisms could contribute to properties observed during unit recording, including grid cell firing, and how they could underlie behavioural functions including path integration. The interaction of oscillations and persistent firing could contribute to encoding and retrieval of trajectories through space and time as a mechanism relevant to episodic memory.

Low- and high-frequency membrane potential oscillations during theta activity in CA1 and CA3 pyramidal neurons of the rat hippocampus under ketamine-xylazine anesthesia

1993 ◽  
Vol 70 (1) ◽  
pp. 97-116 ◽  
Author(s):  
I. Soltesz ◽  
M. Deschenes
Keyword(s):  
Membrane Potential ◽  
Phase Difference ◽  
High Frequency ◽  
Theta Rhythm ◽  
Pyramidal Neurons ◽  
Potential Oscillations ◽  
Eeg Activity ◽  
Intracellular Injection ◽  
Voltage Dependent ◽  
Membrane Potential Oscillations

1. Intracellularly recorded low- and high-frequency (4-6 and 25-50 Hz, respectively), rhythmic, spontaneous membrane potential oscillations were investigated in pyramidal neurons of the rat hippocampus in vivo, during theta (theta, 4-6 Hz) electroencephalographic (EEG) activity, under ketamine-xylazine anesthesia. 2. The EEG activity showed two spectral peaks, one in the theta range, the other at higher frequencies (25-50 Hz). On the basis of their electrophysiological and pharmacological properties, it was concluded that the EEG theta-waves, and the fast EEG rhythm, recorded during ketamine-xylazine anesthesia, share the basic properties of those theta and fast rhythms that are recorded under the effects of other types of anesthetics. 3. When intracellular recordings (n = 32) were made with electrodes filled with potassium-acetate (K-acetate), the only CA1 and CA3 pyramidal cells (PCs) considered for further analysis were those that did not fire rhythmically at most or each cycle of the theta rhythm at the resting membrane potential. During EEG-theta, the membrane potential (Vm) of these cells showed a prominent oscillation (3-15 mV) with frequencies similar to those of the EEG-theta (the intracellular theta rhythm, intra-theta). 4. The frequency of the intra-theta was independent of the Vm. However, the phase difference between the intra-theta and the EEG-theta was voltage dependent in both types of cells. CA1 PCs showed a large (120-180 degrees, where 360 degrees is the full cycle), gradual shift in the phase difference between the intra-theta and the EEG-theta, when the membrane was hyperpolarized to -85 from -65 mV. Although CA3 PCs displayed a larger variability in their phase-voltage relations, a voltage-dependent phase shift (90-180 degrees) could be observed in CA3 PCs as well. 5. Although the amplitude of the intra-theta in both CA1 and CA3 PCs could display large, sudden, spontaneous changes at a given Vm, the amplitude-Vm plots tended to show a minimum between -70 and -80 mV. Spontaneous changes in the amplitude of the intra-theta did not affect the phase difference between the intra- and the EEG-theta rhythms. 6. Intracellular injection of QX-314 (50-100 mM) did not change the phase-Vm or the amplitude-Vm relationships of CA1 PCs. 7. Intracellular injection of chloride (Cl-) ions greatly reduced the voltage dependency of the phase difference and revealed fast (duration: 20-25 ms), depolarizing potentials (5-20 mV), which appeared at high frequencies (25-50 Hz), amplitude modulated at theta-frequencies.(ABSTRACT TRUNCATED AT 400 WORDS)

Endogenous release of 5-HT modulates the plateau phase of NMDA-induced membrane potential oscillations in lamprey spinal neurons

2014 ◽  
Vol 112 (1) ◽  
pp. 30-38 ◽  
Author(s):  
Di Wang ◽  
Sten Grillner ◽  
Peter Wallén
Keyword(s):  
Spinal Cord ◽  
Membrane Potential ◽  
Calcium Channels ◽  
Nmda Receptors ◽  
Plateau Phase ◽  
Spinal Neurons ◽  
Potential Oscillations ◽  
Voltage Dependent ◽  
Endogenous Release ◽  
Membrane Potential Oscillations

The lamprey central nervous system has been used extensively as a model system for investigating the networks underlying vertebrate motor behavior. The locomotor networks can be activated by application of glutamate agonists, such as N-methyl-D-aspartic acid (NMDA), to the isolated spinal cord preparation. Many spinal neurons are capable of generating pacemaker-like membrane potential oscillations upon activation of NMDA receptors. These oscillations rely on the voltage-dependent properties of NMDA receptors in interaction with voltage-dependent potassium and calcium-dependent potassium (KCa) channels, as well as low voltage-activated calcium channels. Upon membrane depolarization, influx of calcium will activate KCa channels, which in turn, will contribute to repolarization and termination of the depolarized phase. The appearance of the NMDA-induced oscillations varies markedly between spinal cord preparations; they may either have a pronounced, depolarized plateau phase or be characterized by a short-lasting depolarization lasting approximately 200–300 ms without a plateau. Both types of oscillations increase in frequency with increased concentrations of NMDA. Here, we characterize these two types of membrane potential oscillations and show that they depend on the level of endogenous release of 5-HT in the spinal cord preparations. In the lamprey, 5-HT acts to block voltage-dependent calcium channels and will thereby modulate the activity of KCa channels. When 5-HT antagonists were administered, the plateau-like oscillations were converted to the second type of oscillations lacking a plateau phase. Conversely, plateau-like oscillations can be induced or prolonged by 5-HT agonists. These properties are most likely of significance for the modulatory action of 5-HT on the spinal networks for locomotion.

Oscillatory Membrane Potential Activity in the Soma of a Primary Afferent Neuron

1999 ◽  
Vol 82 (3) ◽  
pp. 1465-1476 ◽  
Author(s):  
Cristina M. Pedroarena ◽  
Inés E. Pose ◽  
Jack Yamuy ◽  
Michael H. Chase ◽  
Francisco R. Morales
Keyword(s):  
Membrane Potential ◽  
High Frequency ◽  
Present Report ◽  
Oscillatory Activity ◽  
Repetitive Firing ◽  
Afferent Neuron ◽  
Primary Afferent ◽  
Potential Oscillations ◽  
Adult Rat ◽  
Voltage Dependent

In the present report, we provide evidence that mesencephalic trigeminal (Mes-V) sensory neurons, a peculiar type of primary afferent cell with its cell body located within the CNS, may operate in different functional modes depending on the degree of their membrane polarization. Using intracellular recording techniques in the slice preparation of the adult rat brain stem, we demonstrate that when these neurons are depolarized, they exhibit sustained, high-frequency, amplitude-modulated membrane potential oscillations. Under these conditions, the cells discharge high-frequency trains of spikes. Oscillations occur at membrane potential levels more depolarized than −53 ± 2.3 mV (mean ± SD). The amplitude of these oscillations increases with increasing levels of membrane depolarization. The peak-to-peak amplitude of these waves is ∼3 mV when the cells are depolarized to levels near threshold for repetitive firing. The frequency of oscillations is similar in different neurons (108.9 ± 15.5 Hz) and was not modified, in any individual neuron, by changes in the membrane potential level. These oscillations are abolished by hyperpolarization and by TTX, whereas blockers of voltage-dependent K+ currents slow the frequency of oscillations but do not abolish the activity. These data indicate that the oscillations are generated by the activation of inward Na+ current/s and shaped by voltage-dependent K+ outward currents. The oscillatory activity is not modified by perfusion with low-calcium, high-magnesium, or cobalt-containing solutions nor is it modified in the presence of cadmium or Apamin. These results indicate that a calcium-dependent K+ current does not play a significant role in this activity. We postulate that the membrane oscillatory activity in Mes-V neurons is synchronized in adjoining electrotonically coupled cells and that this activity may be modulated in the behaving animal by synaptic influences.

scholarly journals Voltage‐dependent membrane potential oscillations of rat striatal fast‐spiking interneurons

2003 ◽  
Vol 549 (1) ◽  
pp. 121-130 ◽  
Author(s):  
Enrico Bracci ◽  
Diego Centonze ◽  
Giorgio Bernardi ◽  
Paolo Calabresi
Keyword(s):  
Membrane Potential ◽  
Potential Oscillations ◽  
Voltage Dependent ◽  
Fast Spiking ◽  
Membrane Potential Oscillations

Cell-Type–Specific Modulation of Intrinsic Firing Properties and Subthreshold Membrane Oscillations by the M(Kv7)-Current in Neurons of the Entorhinal Cortex

2007 ◽  
Vol 98 (5) ◽  
pp. 2779-2794 ◽  
Author(s):  
Motoharu Yoshida ◽  
Angel Alonso
Keyword(s):  
Membrane Potential ◽  
Entorhinal Cortex ◽  
Intrinsic Excitability ◽  
Cell Type ◽  
Potential Oscillations ◽  
Principal Cells ◽  
M Current ◽  
Current Block ◽  
Layer V ◽  
Membrane Potential Oscillations

The M-current (current through Kv7 channels) is a low-threshold noninactivating potassium current that is suppressed by muscarinic agonists. Recent studies have shown its role in spike burst generation and intrinsic subthreshold theta resonance, both of which are important for memory function. However, little is known about its role in principal cells of the entorhinal cortex (EC). In this study, using whole cell patch recording techniques in a rat EC slice preparation, we have examined the effects of the M-current blockers linopirdine and XE991 on the membrane dynamics of principal cells in the EC. When the M-current was blocked, layer II nonstellate cells (non-SCs) and layer III cells switched from tonic discharge to intermittent firing mode, during which layer II non-SCs showed high-frequency short-duration spike bursts due to increased fast spike afterdepolarization (ADP). When three spikes were elicited at 50 Hz, these two types of cells reacted with a slow ADP that drove delayed firing. In contrast, layer II stellate cells (SCs) and layer V cells never displayed intermittent firing, bursting behavior, or delayed firing. Under the M-current block, intrinsic excitability increased significantly in layer III and layer V cells but not in layer II SCs and non-SCs. The M-current block also had contrasting effects on the subthreshold excitability, greatly suppressing the subthreshold membrane potential oscillations in layer V cells but not in layer II SCs. Modulation of the M-current thus shifts the firing behavior, intrinsic excitability, and subthreshold membrane potential oscillations of EC principal cells in a cell-type–dependent manner.

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