Hyperexcitability of entorhinal cortex and hippocampus after application of aminooxyacetic acid (AOAA) to layer III of the rat medial entorhinal cortex in vitro

1996 ◽  
Vol 76 (5) ◽  
pp. 2986-3001 ◽  
Author(s):  
H. E. Scharfman
Keyword(s):  
Nmda Receptor ◽  
Evoked Potentials ◽  
Entorhinal Cortex ◽  
Pyramidal Cells ◽  
Aminooxyacetic Acid ◽  
Field Potentials ◽  
Medial Entorhinal Cortex ◽  
Extracellular Recordings ◽  
Extracellular Potentials

1. Injection of aminooxyacetic acid (AOAA) into the entorhinal cortex in vivo produces acute seizures and cell loss in medial entorhinal cortex. To understand these effects, AOAA was applied directly to the medial entorhinal cortex in slices containing both the entorhinal cortex and hippocampus. Extracellular and intracellular recordings were made in both the entorhinal cortex and hippocampus to study responses to angular bundle stimulation and spontaneous activity. 2. AOAA was applied focally by leak from a micropipette or by pressure ejection. Evoked potentials increased gradually within 5 min of application, particularly the late, negative components. Evoked potentials continued to increase for up to 1 h, and these changes persisted for the remainder of the experiment (up to 5 h after drug application). 3. Paired pulse facilitation (100-ms interval) was also enhanced after AOAA application. Increasing stimulus frequency to 1-10 Hz increased evoked potentials further, and after several seconds of such stimulation multiple field potentials occurred. When stimulation was stopped at this point, repetitive field potentials occurred spontaneously for 1-2 min. These recordings, and simultaneous extracellular recordings in different layers, indicated that spontaneous synchronous activity occurred in entorhinal neurons. Intracellularly labeled cortical pyramidal cells depolarized and discharged during spontaneous and evoked field potentials. 4. The effects of AOAA were blocked reversibly by bath application of the N-methyl-D-aspartate (NMDA) receptor antagonist D-amino-5-phosphonovalerate (D-APV; 25 microM) or focal application of D-APV to the medial entorhinal cortex. 5. Simultaneous extracellular recordings from the entorhinal cortex and hippocampus demonstrated that spontaneous synchronous activity in layer III was often followed within several milliseconds by negative field potentials in the terminal zones of the perforant path (stratum moleculare of the dentate gyrus and stratum lacunosum-moleculare of area CA1). The extracellular potentials recorded in the dentate gyrus corresponded to excitatory postsynaptic potentials and action potentials in dentate granule cells. However, extracellular potentials in area CA1 were small and rarely correlated with discharge in CA1 pyramidal cells. 6. The results demonstrate that AOAA application leads to an NMDA-receptor-dependent enhancement of evoked potentials in medial entorhinal cortical neurons, which appears to be irreversible. The potentials can be facilitated by repetitive stimulation, and lead to synchronized discharges of entorhinal neurons. The discharges invade other areas such as the hippocampus, indicating how seizure activity may spread after AOAA injection in vivo. These data suggest that AOAA may be a useful tool to study longlasting changes in NMDA receptor function that lead to epileptiform activity and neurodegeneration.

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)

scholarly journals P2-071: IMPAIRED IN VIVO GAMMA OSCILLATIONS IN THE MEDIAL ENTORHINAL CORTEX OF KNOCK-IN ALZHEIMER MODEL

2019 ◽  
Vol 15 ◽  
pp. P598-P598
Author(s):  
Heechul Jun ◽  
Shogo Soma ◽  
Ananya Dasgupta ◽  
Kei Igarashi
Keyword(s):  
Entorhinal Cortex ◽  
Gamma Oscillations ◽  
Medial Entorhinal Cortex

Characterizing interneuron and pyramidal cells in the human medial temporal lobe in vivo using extracellular recordings

Hippocampus ◽  
2006 ◽  
Vol 17 (1) ◽  
pp. 49-57 ◽  
Author(s):  
Indre V. Viskontas ◽  
Arne D. Ekstrom ◽  
Charles L. Wilson ◽  
Itzhak Fried
Keyword(s):  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Pyramidal Cells ◽  
Extracellular Recordings

scholarly journals How to build a grid cell

2014 ◽  
Vol 369 (1635) ◽  
pp. 20120520 ◽  
Author(s):  
Christoph Schmidt-Hieber ◽  
Michael Häusser
Keyword(s):  
Entorhinal Cortex ◽  
Action Potentials ◽  
Path Integration ◽  
Grid Cell ◽  
Medial Entorhinal Cortex ◽  
Synaptic Inputs ◽  
New Findings ◽  
Cell Firing

Neurons in the medial entorhinal cortex fire action potentials at regular spatial intervals, creating a striking grid-like pattern of spike rates spanning the whole environment of a navigating animal. This remarkable spatial code may represent a neural map for path integration. Recent advances using patch-clamp recordings from entorhinal cortex neurons in vitro and in vivo have revealed how the microcircuitry in the medial entorhinal cortex may contribute to grid cell firing patterns, and how grid cells may transform synaptic inputs into spike output during firing field crossings. These new findings provide key insights into the ingredients necessary to build a grid cell.

scholarly journals Spike afterpotentials shape the in-vivo burst activity of principal cells in medial entorhinal cortex

2019 ◽  
Author(s):  
Dóra É. Csordás ◽  
Caroline Fischer ◽  
Johannes Nagele ◽  
Martin Stemmler ◽  
Andreas V.M. Herz
Keyword(s):  
Entorhinal Cortex ◽  
High Frequency ◽  
Cell Group ◽  
Two Dimensional ◽  
Grid Cells ◽  
Spatial Coding ◽  
Medial Entorhinal Cortex ◽  
Whole Cell

AbstractPrincipal neurons in rodent medial entorhinal cortex (MEC) generate high-frequency bursts during natural behavior. While in vitro studies point to potential mechanisms that could support such burst sequences, it remains unclear whether these mechanisms are effective under in-vivo conditions. In this study, we focused on the membrane-potential dynamics immediately following action potentials, as measured in whole-cell recordings from male mice running in virtual corridors (Domnisoru et al., 2013). These afterpotentials consisted either of a hyperpolarization, an extended ramp-like shoulder, or a depolarization reminiscent of depolarizing afterpotentials (DAPs) recorded in vitro in MEC stellate and pyramidal neurons. Next, we correlated the afterpotentials with the cells’ propensity to fire bursts. All DAP cells with known location resided in Layer II, generated bursts, and their inter-spike intervals (ISIs) were typically between five and fifteen milliseconds. The ISI distributions of Layer-II cells without DAPs peaked sharply at around four milliseconds and varied only minimally across that group. This dichotomy in burst behavior is explained by cell-group-specific DAP dynamics. The same two groups of bursting neurons also emerged when we clustered extracellular spike-train autocorrelations measured in real two-dimensional arenas (Latuske et al., 2015). No difference in the spatial coding properties of the grid cells across all three groups was discernible. Layer III neurons were only sparsely bursting and had no DAPs. As various mechanisms for modulating the ion-channels underlying DAPs exist, our results suggest that the temporal features of MEC activity can be altered while maintaining the cells’ spatial tuning characteristics.Significance StatementDepolarizing afterpotentials (DAPs) are frequently observed in principal neurons from slice preparations of rodent medial entorhinal cortex (MEC), but their functional role in vivo is unknown. Analyzing whole-cell data from mice running on virtual tracks, we show that DAPs do occur during behavior. Cells with prominent DAPs are found in Layer II; their inter-spike intervals reflect DAP time-scales. In contrast, neither the rarely bursting cells in Layer III, nor the high-frequency bursters in Layer II, have a DAP. Extracellular recordings from mice exploring real two-dimensional arenas demonstrate that grid cells within these three groups have rather similar spatial coding properties. We conclude that DAPs shape the temporal but not the spatial response characteristics of principal neurons in MEC.Author contributionsAll authors designed research. DÉC, CF, and JN performed research and analyzed data (equal contribution). AVMH wrote and edited the paper with support from MS and the other authors.

scholarly journals Theta-frequency resonance as the scale of input-output mapping in the medial entorhinal cortex

2018 ◽  
Author(s):  
Nupur Katyare ◽  
Sujit Sikdar
Keyword(s):  
Firing Rate ◽  
Entorhinal Cortex ◽  
Grid Cell ◽  
Synaptic Activity ◽  
Spatial Period ◽  
Hcn Channels ◽  
Medial Entorhinal Cortex ◽  
Frequency Resonance ◽  
Theta Frequency

Grid cell spatial period is thought to be dictated by a mapping between the speed-direction modulated excitatory inputs, and consequent modulation of the firing rate, yet, the exact underlying mechanisms are not known. Here, through experiments on the medial entorhinal cortex stellate cells, subjected to in-vivo like stochastic synaptic activity through the dynamic clamp, we show that such mapping can emerge from a theta-frequency resonance in the signal gain, which is HCN sensitive, robust to noise, and is potent enough to modulate the synaptic responses in the theta frequency. This modulation also extends to the corresponding theta-gamma modulation of the firing rate, the slope of whose excitation mediated increase is steeper in the presence of HCN channels. We also show that in the cells devoid of HCN channels, inhibition can emulate their role. Considering the dorso-ventral gradients of HCN and inhibition, which are present aligned to the grid spacing gradient in the medial entorhinal cortex, these findings should be noteworthy.

Frequency Selectivity of Layer II Stellate Cells in the Medial Entorhinal Cortex

2002 ◽  
Vol 88 (5) ◽  
pp. 2422-2429 ◽  
Author(s):  
Julie S. Haas ◽  
John A. White
Keyword(s):  
Entorhinal Cortex ◽  
Stellate Cells ◽  
Mechanistic Explanation ◽  
Input Power ◽  
Total Power ◽  
Frequency Content ◽  
Medial Entorhinal Cortex ◽  
Subthreshold Oscillations ◽  
Subthreshold Resonance

Electrophysiologically, stellate cells (SCs) from layer II of the medial entorhinal cortex (MEC) are distinguished by intrinsic 4- to 12-Hz subthreshold oscillations. These oscillations are thought to impose a pattern of slow periodic firing that may contribute to the parahippocampal theta rhythm in vivo. Using stimuli with systematically differing frequency content, we examined supra- and subthreshold responses in SCs with the goal of understanding how their distinctive characteristics shape these responses. In reaction to repeated presentations of identical, pseudo-random stimuli, the reliability (repeatability) of the spiking response in SCs depends critically on the frequency content of the stimulus. Reliability is optimal for stimuli with a greater proportion of power in the 4- to 12-Hz range. The simplest mechanistic explanation of these results is that rhythmogenic subthreshold membrane mechanisms resonate with inputs containing significant power in the 4- to 12-Hz band, leading to larger subthreshold excursions and thus enhanced reliability. However, close examination of responses rules out this explanation: SCs do show clear subthreshold resonance (i.e., selective amplification of inputs with particular frequency content) in response to sinusoidal stimuli, while simultaneously showing a lack of subthreshold resonance in response to the pseudo-random stimuli used in reliability experiments. Our results support a model with distinctive input-output relationships under subthreshold and suprathreshold conditions. For suprathreshold stimuli, SC spiking seems to best reflect the amount of input power in the theta (4–12 Hz) frequency band. For subthreshold stimuli, we hypothesize that the magnitude of subthreshold theta-range oscillations in SCs reflects the total power, across all frequencies, of the input.

Dentate EEG spikes and associated interneuronal population bursts in the hippocampal hilar region of the rat

1995 ◽  
Vol 73 (4) ◽  
pp. 1691-1705 ◽  
Author(s):  
A. Bragin ◽  
G. Jando ◽  
Z. Nadasdy ◽  
M. van Landeghem ◽  
G. Buzsaki
Keyword(s):  
Entorhinal Cortex ◽  
Slow Wave Sleep ◽  
Molecular Layer ◽  
Current Source ◽  
Pyramidal Cells ◽  
Suppressive Effect ◽  
Simultaneous Recording ◽  
Field Potentials ◽  
Electrode Arrays ◽  
Hilar Region

1. This paper describes two novel population patterns in the dentate gyrus of the awake rat, termed type 1 and type 2 dentate spikes (DS1, DS2). Their cellular generation and spatial distribution were examined by simultaneous recording of field potentials and unit activity using multiple-site silicon probes and wire electrode arrays. 2. Dentate spikes were large amplitude (2-4 mV), short duration (< 30 ms) field potentials that occurred sparsely during behavioral immobility and slow-wave sleep. Current-source density analysis revealed large sinks in the outer (DS1) and middle (DS2) thirds of the dentate molecular layer, respectively. DS1 and DS2 had similar longitudinal, lateral, and interhemispheric synchrony. 3. Dentate spikes invariably were coupled to synchronous population bursts of putative hilar interneurons. CA3 pyramidal cells, on the other hand were suppressed during dentate spikes. 4. After bilateral removal of the entorhinal cortex, dentate spikes disappeared, whereas sharp wave-associated bursts, reflecting synchronous discharge of the CA3-CA1 network, increased several fold. 5. These physiological characteristics of the dentate spikes suggest that they are triggered by a population burst of layer II stellate cells of the lateral (DS1) and medial (DS2) entorhinal cortex. 6. We suggest that dentate spike-associated synchronized bursts of hilar-region interneurons provide a suppressive effect on the excitability of the CA3-CA1 network in the intact brain.

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