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

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)

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

Journal of Neurophysiology ◽

10.1152/jn.90351.2008 ◽

2008 ◽

Vol 100 (5) ◽

pp. 2746-2756 ◽

Cited By ~ 14

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.

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

Journal of Neurophysiology ◽

10.1152/jn.2002.87.6.2676 ◽

2002 ◽

Vol 87 (6) ◽

pp. 2676-2683 ◽

Cited By ~ 15

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.

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Local Generation of Theta-Frequency EEG Activity in the Parasubiculum

Journal of Neurophysiology ◽

10.1152/jn.01306.2006 ◽

2007 ◽

Vol 97 (6) ◽

pp. 3868-3879 ◽

Cited By ~ 27

Author(s):

Stephen D. Glasgow ◽

C. Andrew Chapman

Keyword(s):

Membrane Potential ◽

Hippocampal Formation ◽

Brain Slices ◽

Stratum Radiatum ◽

Potential Oscillations ◽

Eeg Activity ◽

Ca1 Region ◽

Adjacent Structures ◽

Theta Frequency ◽

Membrane Potential Oscillations

The parasubiculum is a major component of the hippocampal formation that receives inputs from the CA1 region, anterior thalamus, and medial septum and that projects primarily to layer II of the entorhinal cortex. Hippocampal theta-frequency (4–12 Hz) electroencephalographic (EEG) activity has been correlated with sensorimotor integration, spatial navigation, and memory functions. The present study was aimed at determining if theta is also generated locally within the parasubiculum versus volume conducted from adjacent structures. In urethan-anesthetized rats, the phase-reversal of theta activity between superficial and deep layers of the parasubiculum was demonstrated using differential recordings from movable bipolar electrodes that eliminate the influence of volume-conducted activity. Parasubicular theta was abolished by atropine, and was in phase with theta in stratum radiatum/lacunosum-moleculare of the CA1 region. Whole cell current-clamp recordings in brain slices were then used to determine if parasubicular theta may be generated in part by membrane potential oscillations in layer II neurons. Membrane potential oscillations occurred in most layer II neurons, including four putative interneurons, when cells were held at near-threshold voltages using current injection. The frequency of oscillations increased from 3.2 to 6.1 Hz when bath temperature was raised from 22 to 32°C, and oscillations persisted in the presence of blockers of fast ionotropic glutamatergic and GABAergic synaptic transmission. Oscillations are therefore likely generated by intrinsic, voltage-dependent ionic conductances. These results indicate that theta field activity is generated locally within the parasubiculum and that intrinsic membrane potential oscillations, synchronized by local inhibitory inputs, may contribute to the generation of this activity.

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

Journal of Neurophysiology ◽

10.1152/jn.00582.2013 ◽

2014 ◽

Vol 112 (1) ◽

pp. 30-38 ◽

Cited By ~ 9

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.

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

Journal of Neurophysiology ◽

10.1152/jn.1999.82.3.1465 ◽

1999 ◽

Vol 82 (3) ◽

pp. 1465-1476 ◽

Cited By ~ 41

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.

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