Spike Timing of Lacunosom-Moleculare Targeting Interneurons and CA3 Pyramidal Cells During High-Frequency Network Oscillations In Vitro

2007 ◽  
Vol 98 (1) ◽  
pp. 96-104 ◽  
Author(s):  
Jay Spampanato ◽  
Istvan Mody
Keyword(s):  
High Frequency ◽  
Epileptiform Activity ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Gamma Oscillations ◽  
Spike Timing ◽  
Network Activity ◽  
Network Oscillations ◽  
Ca3 Pyramidal Cells

Network activity in the 200- to 600-Hz range termed high-frequency oscillations (HFOs) has been detected in epileptic tissue from both humans and rodents and may underlie the mechanism of epileptogenesis in experimental rodent models. Slower network oscillations including theta and gamma oscillations as well as ripples are generated by the complex spike timing and interactions between interneurons and pyramidal cells of the hippocampus. We determined the activity of CA3 pyramidal cells, stratum oriens lacunosum-moleculare (O-LM) and s. radiatum lacunosum-moleculare (R-LM) interneurons during HFO in the in vitro low-Mg2+ model of epileptiform activity in GIN mice. In these animals, interneurons can be identified prior to cell-attached recordings by the expression of green-fluorescent protein (GFP). Simultaneous local field potential recordings from s. pyramidale and on-cell recordings of individual interneurons and principal cells revealed three primary firing behaviors of the active cells: 36% of O-LM interneurons and 60% of pyramidal cells fired action potentials at high frequencies during the HFO. R-LM interneurons were biphasic in that they fired at high frequency at the beginning of the HFO but stopped firing before its end. When considering only the highest frequency component of the oscillations most pyramidal cells fired on the rising phase of the oscillation. These data provide evidence for functional distinction during HFOs within otherwise homogeneous groups of O-LM interneurons and pyramidal cells.

scholarly journals Impaired long-range synchronization of gamma oscillations in the neocortex of a mouse lacking Kv3.2 potassium channels

2012 ◽  
Vol 108 (3) ◽  
pp. 827-833 ◽  
Author(s):  
Michael Harvey ◽  
David Lau ◽  
Eugene Civillico ◽  
Bernardo Rudy ◽  
Diego Contreras
Keyword(s):  
Long Range ◽  
High Frequency ◽  
Single Cells ◽  
Critical Role ◽  
Pyramidal Cells ◽  
Gamma Oscillations ◽  
Network Activity ◽  
Inhibitory Interneurons ◽  
Phase Lag ◽  
Firing Properties

Inhibitory interneurons play a critical role in the generation of gamma (20–50 Hz) oscillations, either by forming mutually inhibitory networks or as part of recurrent networks with pyramidal cells. A key property of fast spiking interneurons is their ability to generate brief spikes and high-frequency spike trains with little accommodation. However, the role of their firing properties in network oscillations has not been tested in vivo. Studies in hippocampus in vitro have shown that high-frequency spike doublets in interneurons play a key role in the long-range synchronization of gamma oscillations with little phase lag despite long axonal conduction delays. We generated a knockout (KO) mouse lacking Kv3.2 potassium channel subunits, where infragranular inhibitory interneurons lose the ability both to sustain high-frequency firing and reliably generate high-frequency spike doublets. We recorded cortical local field potentials in anesthetized and awake, restrained mice. Spontaneous activity of the KO and the wild-type (WT) showed similar content of gamma and slow (0.1–15 Hz) frequencies, but the KO showed a significantly larger decay of synchronization of gamma oscillations with distance. Coronal cuts in the cortex of WT mice decreased synchronization to values similar to the intact KO. The synchronization of the slow oscillation showed little decay with distance in both mice and was largely reduced after coronal cuts. Our results show that the firing properties of inhibitory interneurons are critical for long-range synchronization of gamma oscillations, and emphasize that intrinsic electrophysiological properties of single cells may play a key role in the spatiotemporal characteristics of network activity.

scholarly journals Oxygen Consumption Rates during Three Different Neuronal Activity States in the Hippocampal CA3 Network

2012 ◽  
Vol 33 (2) ◽  
pp. 263-271 ◽  
Author(s):  
Christine Huchzermeyer ◽  
Nikolaus Berndt ◽  
Hermann-Georg Holzhütter ◽  
Oliver Kann
Keyword(s):  
Oxygen Consumption ◽  
Field Potential ◽  
Gamma Oscillations ◽  
Convective Transport ◽  
Energy Utilization ◽  
Network Activity ◽  
Gas Mixture ◽  
Network Oscillations ◽  
Consumption Rates ◽  
Fast Network

The brain is an organ with high metabolic rate. However, little is known about energy utilization during different activity states of neuronal networks. We addressed this issue in area CA3 of hippocampal slice cultures under well-defined recording conditions using a 20% O2 gas mixture. We combined recordings of local field potential and interstitial partial oxygen pressure (pO2) during three different activity states, namely fast network oscillations in the gamma-frequency band (30 to 100 Hz), spontaneous network activity and absence of spiking (action potentials). Oxygen consumption rates were determined by pO2 depth profiles with high spatial resolution and a mathematical model that considers convective transport, diffusion, and activity-dependent consumption of oxygen. We show that: (1) Relative oxygen consumption rate during cholinergic gamma oscillations was 2.2-fold and 5.3-fold higher compared with spontaneous activity and absence of spiking, respectively. (2) Gamma oscillations were associated with a similar large decrease in pO2 as observed previously with a 95% O2 gas mixture. (3) Sufficient oxygenation during fast network oscillations in vivo is ensured by the calculated critical radius of 30 to 40 μm around a capillary. We conclude that the structural and biophysical features of brain tissue permit variations in local oxygen consumption by a factor of about five.

scholarly journals Evidence that PV+ cells enhance temporal population codes but not stimulus-related timing in auditory cortex

2017 ◽  
Author(s):  
Bryan M. Krause ◽  
Caitlin A. Murphy ◽  
Daniel J. Uhlrich ◽  
Matthew I. Banks
Keyword(s):  
Brain Slices ◽  
Pyramidal Cells ◽  
Gamma Oscillations ◽  
Cortical Activity ◽  
Spike Timing ◽  
Network Activity ◽  
Local Network ◽  
Network Bursts ◽  
Spatio Temporal

AbstractSpatio-temporal cortical activity patterns relative to both peripheral input and local network activity carry information about stimulus identity and context. GABAergic interneurons are reported to regulate spiking at millisecond precision in response to sensory stimulation and during gamma oscillations; their role in regulating spike timing during induced network bursts is unclear. We investigated this issue in murine auditory thalamo-cortical (TC) brain slices, in which TC afferents induced network bursts similar to previous reports in vivo. Spike timing relative to TC afferent stimulation during bursts was poor in pyramidal cells and SOM+ interneurons. It was more precise in PV+ interneurons, consistent with their reported contribution to spiking precision in pyramidal cells. Optogenetic suppression of PV+ cells unexpectedly improved afferent-locked spike timing in pyramidal cells. In contrast, our evidence suggests that PV+ cells do regulate the spatio-temporal spike pattern of pyramidal cells during network bursts, whose organization is suited to ensemble coding of stimulus information. Simulations showed that suppressing PV+ cells reduces the capacity of pyramidal cell networks to produce discriminable spike patterns. By dissociating temporal precision with respect to a stimulus versus internal cortical activity, we identified a novel role for GABAergic cells in regulating information processing in cortical networks.

scholarly journals Synaptic GABAA Activation Inhibits AMPA-Kainate Receptor–Mediated Bursting in the Newborn (P0–P2) Rat Hippocampus

2000 ◽  
Vol 83 (1) ◽  
pp. 359-366 ◽  
Author(s):  
Karri Lamsa ◽  
J. Matias Palva ◽  
Eva Ruusuvuori ◽  
Kai Kaila ◽  
Tomi Taira
Keyword(s):  
Pyramidal Neurons ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Neuronal Population ◽  
Excitatory Input ◽  
Calcium Oscillations ◽  
Rat Hippocampus ◽  
Network Activity ◽  
Ca1 Pyramidal Cells

The mechanisms of synaptic transmission in the rat hippocampus at birth are assumed to be fundamentally different from those found in the adult. It has been reported that in the CA3-CA1 pyramidal cells a conversion of “silent” glutamatergic synapses to conductive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) synapses starts gradually after P2. Further, GABA via its depolarizing action seems to give rise to grossly synchronous yet slow calcium oscillations. Therefore, GABA is generally thought to have a purely excitatory rather than an inhibitory role during the first postnatal week. In the present study field potential recordings and gramicidin perforated and whole cell clamp techniques as well as K+-selective microelectrodes were used to examine the relative contributions of AMPA and GABAA receptors to network activity of CA3-CA1 pyramidal cells in the newborn rat hippocampus. As early as postnatal day( P 0–P2), highly coherent spontaneous firing of CA3 pyramidal cells was seen in vitro. Negative-going extracellular spikes confined to periodic bursts (interval 16 ± 3 s) consisting of 2.9 ± 0.1 spikes were observed in stratum pyramidale. The spikes were accompanied by AMPA-R–mediated postsynaptic currents (PSCs) in simultaneously recorded pyramidal neurons (7.6 ± 3.0 unitary currents per burst). In CA1 pyramidal cells synchronous discharging of CA3 circuitry produced a barrage of AMPA currents at >20 Hz frequencies, thus demonstrating a transfer of the fast CA3 network activity to CA1 area. Despite its depolarizing action, GABAA-R–mediated transmission appeared to exert inhibition in the CA3 pyramidal cell population. The GABAA-R antagonist bicuculline hypersynchronized the output of glutamatergic CA3 circuitry and increased the network-driven excitatory input to the pyramidal neurons, whereas the GABAA-R agonist muscimol (100 nM) did the opposite. However, the occurrence of unitary GABAA-R currents was increased after muscimol application from 0.66 ± 0.16 s−1 to 1.43 ± 0.29 s−1. It was concluded that AMPA synapses are critical in the generation of spontaneous high-frequency bursts in CA3 as well as in CA3-CA1 transmission as early as P0–P2 in rat hippocampus. Concurrently, although GABAA-R–mediated depolarization may excite hippocampal interneurons, in CA3 pyramidal neurons it can restrain excitatory inputs and limit the size of the activated neuronal population.

Heterogeneous firing behavior during ictal-like epileptiform activity in vitro

2012 ◽  
Vol 107 (5) ◽  
pp. 1379-1392 ◽  
Author(s):  
Mogens Andreasen ◽  
Steen Nedergaard
Keyword(s):  
High Frequency ◽  
Critical Mass ◽  
Epileptiform Activity ◽  
Pyramidal Cells ◽  
Type I ◽  
Population Activity ◽  
Type Iii ◽  
Plateau Potential ◽  
Potential Type

Seizure activity in vivo is caused by populations of neurons displaying a high degree of variability in activity pattern during the attack. The reason for this variability is not well understood. Here we show in an in vitro preparation that hippocampal CA1 pyramidal cells display four types of afterdischarge behavior during stimulus-induced ictal-like events in the presence of Cs+ (5 mM): type I (43.7%) consisting of high-frequency firing riding on a plateau potential; type II (28.2%) consisting of low-frequency firing with no plateau potential; type III (18.3%) consisting of high-frequency firing with each action potential preceded by a transient hyperpolarization and time-locked to population activity, no plateau potential; “passive” (9.9%) typified by no afterdischarge. Type I behavior was blocked by TTX (0.2 μM) and intracellular injection of QX314 (12.5–25 mM). TTX (0.2 μM) or phenytoin (50 μM) terminated ictal-like events, suggesting that the persistent Na+ current ( INaP) is pivotal for type I behavior. Type I behavior was not correlated to intrinsic bursting capability. Blockade of the M current ( IM) with linopirdine (10 μM) increased the ratio of type I neurons to 100%, whereas enhancing IM with retigabine (50–100 μM) greatly reduced the epileptiform activity. These results suggest an important role of IM in determining afterdischarge behavior through control of INaP expression. We propose that type I neurons act as pacemakers, which, through synchronization, leads to recruitment of type III neurons. Together, they provide the “critical mass” necessary for ictogenesis to become regenerative.

scholarly journals In vivo characterization and application of a novel potassium channel-based optogenetic silencer in the healthy and epileptic mouse hippocampus

2021 ◽  
Author(s):  
Piret Kleis ◽  
Enya Paschen ◽  
Ute Haeussler ◽  
Yinth Andrea Bernal Sierra ◽  
Carola A. Haas
Keyword(s):  
Side Effects ◽  
Potassium Channel ◽  
Neuronal Activity ◽  
Viral Vector ◽  
Epileptiform Activity ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Light Sensitivity

The performance of available optogenetic inhibitors remains insufficient due to low light sensitivity, short-lasting photocurrents, and unintended changes in ion distributions. To overcome these limitations, a novel potassium channel-based optogenetic silencer was developed and successfully applied in various in vitro and acute in vivo settings (Bernal Sierra et al., 2018). This tool, a two-component construct called PACK, comprises a photoactivated adenylyl cyclase (bPAC) and a cAMP-dependent potassium channel (SthK). Here, we examined the long-term inhibitory action and side effects of the PACK construct in healthy and epileptic adult male mice. We targeted hippocampal CA1 pyramidal cells using a viral vector and enabled illumination of these neurons via an implanted optic fiber. Local field potential (LFP) recordings from the CA1 of freely moving mice revealed significantly reduced neuronal activity during 50-minute intermittent illumination, especially in the beta and gamma frequency ranges. Adversely, PACK expression in healthy mice induced chronic astrogliosis, dispersion of pyramidal cells, and generalized seizures. These side effects were independent of the light application and were also present in mice expressing bPAC without the potassium channel. Additionally, light-activation of bPAC alone increased neuronal activity, presumably via enhanced cAMP signaling. In chronically epileptic mice, the dark activity of bPAC/PACK in CA1 prevented the spread of spontaneous epileptiform activity from the seizure focus to the contralateral bPAC/PACK-expressing hippocampus. Taken together, the PACK tool is a potent optogenetic inhibitor but requires refinement of its light-sensitive domain to avoid unexpected physiological changes.

Aluminum Suppresses Effect of Nicotine on Gamma Oscillations (20-40 Hz) in Mouse Hippocampal Slices

2018 ◽  
Vol 17 (6) ◽  
pp. 404-411 ◽  
Author(s):  
Syeda Mehpara Farhat ◽  
Touqeer Ahmed
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Cholinergic System ◽  
Acetylcholine Receptors ◽  
Peak Power ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Gamma Oscillations ◽  
Gamma Oscillation ◽  
Facilitatory Effect

Background: Aluminum (Al) causes neurodegeneration and its toxic effects on cholinergic system in the brain is well documented. However, it is unknown whether and how Al changes oscillation patterns, driven by the cholinergic system, in the hippocampus. Objective: We studied acute effects of Al on nicotinic acetylcholine receptors (nAChRs)-mediated modulation of persistent gamma oscillations in the hippocampus. Method: The field potential recording was done in CA3 area of acute hippocampal slices. Results: Carbachol-induced gamma oscillation peak power increased (1.32±0.09mV2/Hz, P<0.01) in control conditions (without Al) by application of 10µM nicotine as compared to baseline value normalized to 1. This nicotine-induced facilitation of gamma oscillation peak power was found to depend on non-α7 nAChRs. In slices with Al pre-incubation for three to four hours, gamma oscillation peak power was reduced (5.4±1.8mV2/Hz, P<0.05) and facilitatory effect of nicotine on gamma oscillation peak power was blocked as compared to the control (18.06±2.1mV2/Hz) or one hour Al pre-incubated slices (11.3±2.5mV2/Hz). Intriguingly wash-out, after three to four hours of Al incubation, failed to restore baseline oscillation power and its facilitation by nicotine as no difference was observed in gamma oscillation peak power between Al wash-out slices (3.4±1.1mV2/Hz) and slices without washout (3.6±0.9mV2/Hz). Conclusion: This study shows that at cellular level, exposure of hippocampal tissue to Al compromised nAChR-mediated facilitation of cholinergic hippocampal gamma oscillations. Longer in vitro Al exposure caused permanent changes in hippocampal oscillogenic circuitry and changed its sensitivity to nAChR-modulation. This study will help to understand the possible mechanism of cognitive decline induced by Al.

Generation of Slow Network Oscillations in the Developing Rat Hippocampus After Blockade of Glutamate Uptake

2007 ◽  
Vol 98 (4) ◽  
pp. 2324-2336 ◽  
Author(s):  
Adriano Augusto Cattani ◽  
Valérie Delphine Bonfardin ◽  
Alfonso Represa ◽  
Yehezkel Ben-Ari ◽  
Laurent Aniksztejn
Keyword(s):  
Nmda Receptors ◽  
Glutamate Uptake ◽  
Pyramidal Cells ◽  
Cell Types ◽  
Proper Function ◽  
Network Oscillations ◽  
Bath Application ◽  
Hippocampal Network

Cell-surface glutamate transporters are essential for the proper function of early cortical networks because their dysfunction induces seizures in the newborn rat in vivo. We have now analyzed the consequences of their inhibition by dl-TBOA on the activity of the developing CA1 rat hippocampal network in vitro. dl-TBOA generated a pattern of recurrent depolarization with an onset and decay of several seconds' duration in interneurons and pyramidal cells. These slow network oscillations (SNOs) were mostly mediated by γ-aminobutyric acid (GABA) in pyramidal cells and by GABA and N-methyl-d-aspartate (NMDA) receptors in interneurons. However, in both cell types SNOs were blocked by NMDA receptor antagonists, suggesting that their generation requires a glutamatergic drive. Moreover, in interneurons, SNOs were still generated after the blockade of NMDA-mediated synaptic currents with MK-801, suggesting that SNOs are expressed by the activation of extrasynaptic NMDA receptors. Long-lasting bath application of glutamate or NMDA failed to induce SNOs, indicating that they are generated by periodic but not sustained activation of NMDA receptors. In addition, SNOs were observed in interneurons recorded in slices with or without the strata pyramidale and oriens, suggesting that the glutamatergic drive may originate from the radiatum and pyramidale strata. We propose that in the absence of an efficient transport of glutamate, the transmitter diffuses in the extracellular space to activate extrasynaptic NMDA receptors preferentially present on interneurons that in turn activate other interneurons and pyramidal cells. This periodic neuronal coactivation may contribute to the generation of seizures when glutamate transport dysfunction is present.

Effect of Common Anesthetics on Dendritic Properties in Layer 5 Neocortical Pyramidal Neurons

2008 ◽  
Vol 99 (3) ◽  
pp. 1394-1407 ◽  
Author(s):  
Sarah Potez ◽  
Matthew E. Larkum
Keyword(s):  
High Frequency ◽  
Pyramidal Neurons ◽  
Animal Experiments ◽  
Apical Dendrite ◽  
Network Activity ◽  
Calcium Spikes ◽  
Firing Properties ◽  
The Impact

Understanding the impact of active dendritic properties on network activity in vivo has so far been restricted to studies in anesthetized animals. However, to date no study has been made to determine the direct effect of the anesthetics themselves on dendritic properties. Here, we investigated the effects of three types of anesthetics commonly used for animal experiments (urethane, pentobarbital and ketamine/xylazine). We investigated the generation of calcium spikes, the propagation of action potentials (APs) along the apical dendrite and the somatic firing properties in the presence of anesthetics in vitro using dual somatodendritic whole cell recordings. Calcium spikes were evoked with dendritic current injection and high-frequency trains of APs at the soma. Surprisingly, we found that the direct actions of anesthetics on calcium spikes were very different. Two anesthetics (urethane and pentobarbital) suppressed dendritic calcium spikes in vitro, whereas a mixture of ketamine and xylazine enhanced them. Propagation of spikes along the dendrite was not significantly affected by any of the anesthetics but there were various changes in somatic firing properties that were highly dependent on the anesthetic. Last, we examined the effects of anesthetics on calcium spike initiation and duration in vivo using high-frequency trains of APs generated at the cell body. We found the same anesthetic-dependent direct effects in addition to an overall reduction in dendritic excitability in anesthetized rats with all three anesthetics compared with the slice preparation.

Nonsynaptic epileptogenesis in the mammalian hippocampus in vitro. I. Development of seizurelike activity in low extracellular calcium

1986 ◽  
Vol 56 (2) ◽  
pp. 409-423 ◽  
Author(s):  
A. Konnerth ◽  
U. Heinemann ◽  
Y. Yaari
Keyword(s):  
Epileptiform Activity ◽  
Large Population ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Discharge Zone ◽  
Critical Threshold ◽  
Mean Velocity ◽  
Stratum Pyramidale ◽  
Ca1 Area

Epileptiform activity induced in rat hippocampal slices by lowering extracellular Ca2+ concentration ([Ca2+]o) was studied with extracellular and intracellular recordings. Perfusing the slices with low Ca2+ (less than or equal to 0.2 mM) or EGTA-containing solutions blocked the synaptic responses of hippocampal pyramidal cells (HPCs). Despite the block, spontaneous paroxysms, termed seizurelike events (SLEs), appeared in the CA1 area and then recurred regularly at a stable frequency. Transient hypoxia accelerated their development and increased their frequency. When [Ca2+]o was raised in a stepwise manner, the SLEs disappeared at 0.3 mM. With extracellular recording from the CA1 stratum pyramidale, a SLE was characterized by a large negative shift in the field potential, which lasted for several seconds. During this period a large population of CA1 neurons discharged intensely and often in synchrony, as concluded from the frequent appearance of population spikes. Synchronization, however, was not a necessary precursor for the development of paroxysmal activity, but seemed to be the end result of massive neuronal excitation. The cellular counterpart of a SLE, as revealed by intracellular recording from HPCs in the discharge zone of the paroxysms, was a long-lasting depolarization shift (LDS) of up to 20 mV. This was accompanied by accelerated firing of the neuron. A prolonged after-hyperpolarization succeeded each LDS and arrested cell firing. Brief (approximately 50 ms) bursts were commonly observed before LDS onset. Single electrical stimuli applied focally to the stratum pyramidale or alveus evoked paroxysms identical to the spontaneous SLEs, provided they surpassed a critical threshold intensity. Subthreshold stimuli elicited only small local responses, whereas stimuli of varied suprathreshold intensities evoked the same maximal SLEs. Thus the buildup of a SLE is an all or nothing or a regenerative process, which mobilizes the majority, if not all, of the local neuronal population. Each SLE was followed by absolute and relative refractory periods during which focal stimulation was, respectively, ineffective and less effective in evoking a maximal SLE. In most slices the spontaneous SLEs commenced at a "focus" located in the CA1a subarea (near the subiculum). SLEs evoked by focal stimulation arose near the stimulating electrode. From their site of origin the paroxysmal discharges spread transversely through the entire CA1 area at a mean velocity of 1.74 mm/s. Consequently, the discharge zone of a SLE could encompass for several seconds the entire CA1 area.(ABSTRACT TRUNCATED AT 400 WORDS)

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