scholarly journals Chloride-Cotransport Blockade Desynchronizes Neuronal Discharge in the “Epileptic” Hippocampal Slice

2000 ◽  
Vol 83 (1) ◽  
pp. 406-417 ◽  
Author(s):  
Daryl W. Hochman ◽  
Philip A. Schwartzkroin
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Extracellular Potassium ◽  
Intracellular Recordings ◽  
Population Activity ◽  
Ca1 Pyramidal Cells ◽  
Epileptiform Discharges

Antagonism of the chloride-cotransport system in hippocampal slices has been shown to block spontaneous epileptiform (i.e., hypersynchronized) discharges without diminishing excitatory synaptic transmission. Here we test the hypotheses that chloride-cotransport blockade, with furosemide or low-chloride (low-[Cl−]o) medium, desynchronizes the firing activity of neuronal populations and that this desynchronization is mediated through nonsynaptic mechanisms. Spontaneous epileptiform discharges were recorded from the CA1 and CA3 cell body layers of hippocampal slices. Treatment with low-[Cl−]o medium led to cessation of spontaneous synchronized bursting in CA1 ≥5–10 min before its disappearance from CA3. During the time that CA3 continued to burst spontaneously but CA1 was silent, electrical stimulation of the Schaffer collaterals showed that hyperexcited CA1 synaptic responses were maintained. Paired intracellular recordings from CA1 pyramidal cells showed that during low-[Cl−]otreatment, the timing of action potential discharges became desynchronized; desynchronization was identified with phase lags in firing times of action potentials between pairs of neurons as well as a with a broadening and diminution of the CA1 field amplitude. Continued exposure to low-[Cl−]o medium increased the degree of the firing-time phase shifts between pairs of CA1 pyramidal cells until the epileptiform CA1 field potential was abolished completely. Intracellular recordings during 4-aminopyridine (4-AP) treatment showed that prolonged low-[Cl−]oexposure did not diminish the frequency or amplitude of spontaneous postsynaptic potentials. CA3 antidromic responses to Schaffer collateral stimulation were not significantly affected by prolonged low-[Cl−]o exposure. In contrast to CA1, paired intracellular recordings from CA3 pyramidal cells showed that chloride-cotransport blockade did not cause a significant desynchronization of action potential firing times in the CA3 subregion at the time that CA1 synchronous discharge was blocked but did reduce the number of action potentials associated with CA3 burst discharges. These data support our hypothesis that the anti-epileptic effects of chloride-cotransport antagonism in CA1 are mediated through the desynchronization of population activity. We hypothesize that interference with Na+,K+,2Cl−cotransport results in an increase in extracellular potassium ([K+]o) that reduces the number of action potentials that are able to invade axonal arborizations and varicosities in all hippocampal subregions. This reduced efficacy of presynaptic action potential propagation ultimately leads to a reduction of synaptic drive and a desynchronization of the firing of CA1 pyramidal cells.

Extracellular Chloride and the Maintenance of Spontaneous Epileptiform Activity in Rat Hippocampal Slices

1999 ◽  
Vol 81 (1) ◽  
pp. 49-59 ◽  
Author(s):  
Daryl W. Hochman ◽  
Raimondo D'Ambrosio ◽  
Damir Janigro ◽  
Philip A. Schwartzkroin
Keyword(s):  
Prolonged Exposure ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Spontaneous Discharge ◽  
Extracellular Potassium ◽  
Ca1 Pyramidal Cells ◽  
Ca1 Region ◽  
Negative Field

Hochman, Daryl W., Raimondo D'Ambrosio, Damir Janigro, and Philip A. Schwartzkroin. Extracellular chloride and the maintenance of spontaneous epileptiform activity in rat hippocampal slices. J. Neurophysiol. 81: 49–59, 1999. Previous studies showed that furosemide blocks spontaneous epileptiform activity without diminishing synaptic transmission or reducing hyperexcited field responses to electrical stimuli. We now test the hypothesis that the antiepileptic effects of furosemide are mediated through its blockade of the Na+,K+,2Cl− cotransporter and thus should be mimicked by a reduction of extracellular chloride ([Cl−]o). In the first set of experiments, field recordings from the CA1 cell body layer of hippocampal slices showed that spontaneous bursting developed within 10–20 min in slices perfused with low-[Cl−]o (7 mM) medium but that this spontaneous epileptiform activity ceased after a further 10–20 min. Intracellular recordings from CA1 pyramidal cells showed that normal action potential discharge could be elicited by membrane depolarization, even after the tissue was perfused with low-[Cl−]o medium for >2 h. In a second set of experiments, spontaneous bursting activity was induced in slices by perfusion with high-[K+]o (10 mM), bicuculline (100 μM), or 4-aminopyridine (100 μM). In each case, recordings from the CA1 region showed that reduction of [Cl−]o to 21 mM reversibly blocked the bursting within 1 h. Similar to previous observations with furosemide treatment, low-[Cl−]o medium blocked spontaneous hypersynchronous discharges without reducing synaptic hyperexcitability (i.e., hyperexcitable field responses evoked by electrical stimulation). In a third set of experiments, prolonged exposure (>1 h after spontaneous bursting ceased) of slices to systematically varied [Cl−]o and [K+]o resulted in one of three types of events: 1) spontaneous, long-lasting, and repetitive negative field potential shifts (7 mM [Cl−]o; 3 mM [K+]o); 2) oscillations consisting of 5- to 10-mV negative shifts in the field potential, with a period of ∼1 cycle/40 s (16 mM [Cl−]o; 12 mM [K+]o); and 3) shorter, infrequently occurring negative field shifts lasting 20–40 s (21 mM [Cl−]o; 3 mM [K+]o). Our observations indicate that the effects of low [Cl−]o on neuronal synchronization and spontaneous discharge are time dependent. Similar effects were seen with furosemide and low [Cl−]o, consistent with the hypothesis that the antiepileptic effect of furosemide is mediated by the drug's effect on chloride transporters. Finally, the results of altering extracellular potassium along with chloride suggest that blockade of the Na+, K+,2Cl− cotransporter, which normally transports chloride from the extracellular space into glial cells, is key to these antiepileptic effects.

Variant firing patterns in rat hippocampal pyramidal cells modulated by extracellular potassium

1994 ◽  
Vol 71 (3) ◽  
pp. 831-839 ◽  
Author(s):  
M. S. Jensen ◽  
R. Azouz ◽  
Y. Yaari
Keyword(s):  
Action Potentials ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Resting Membrane Potential ◽  
Extracellular Potassium ◽  
Differential Distribution ◽  
Ca1 Pyramidal Cells ◽  
Current Pulses ◽  
High K ◽  
Single Spike

1. The distribution of distinctive firing modes within the population of CA1 pyramidal cells and their modulation by the extracellular concentration of potassium ([K+]o) were investigated with intracellular recordings in rat hippocampal slices. 2. Pyramidal cells were injected with long (> 250 ms) and brief (3-5 ms) positive current pulses of increasing intensity. In normal [K+]o (3.5 mM), most cells (38 of 46 cells; 83%) were regular spiking neurons (generating accommodating trains of independent action potentials during long depolarizations and a single spike in response to brief stimuli). The remaining pyramidal cells (8 of 46; 17%) displayed differential tendencies to generate stereotyped clusters of action potentials, or bursts, according to which they were grouped into three subsets of endogenous bursters: grade I, bursting only when stimulated with long depolarizing current pulses (6 of 46; 13%); grade II, bursting also in response to brief stimulation (1 of 46; 2%); grade III, bursting also spontaneously even in absence of synaptic transmission (1 of 46; 2%). 3. Raising [K+]o from 3.5 to 7.5 mM (high [K+]o) significantly reduced resting membrane potential and input impedance but did not change the threshold potential for eliciting an action potential. 4. Raising [K+]o to 7.5 mM reversibly converted many regular spiking cells to bursters. Likewise, the burst tendency of normally bursting pyramidal cells increased to a higher grade in high [K+]o. Consequently, the fraction of bursters in high [K+]o (17 of 41 cells; 42%) was approximately 2.5-fold higher than in normal [K+]o and their differential distribution was shifted toward higher grades of bursting.(ABSTRACT TRUNCATED AT 250 WORDS)

On the synchronous activity induced by 4-aminopyridine in the CA3 subfield of juvenile rat hippocampus

1993 ◽  
Vol 70 (3) ◽  
pp. 1018-1029 ◽  
Author(s):  
M. Avoli ◽  
C. Psarropoulou ◽  
V. Tancredi ◽  
Y. Fueta
Keyword(s):  
Nmda Receptor ◽  
Gabaa Receptor ◽  
Action Potentials ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Occurrence Rate ◽  
Gamma Aminobutyric Acid ◽  
Synchronous Activity ◽  
Ca3 Pyramidal Cells

1. Extracellular field potential and intracellular recordings were made in the CA3 subfield of hippocampal slices obtained from 10- to 24-day-old rats during perfusion with artificial cerebrospinal fluid (ACSF) containing the convulsant 4-aminopyridine (4-AP, 50 microM). 2. Three types of spontaneous, synchronous activity were recorded in the presence of 4-AP by employing extracellular microelectrodes positioned in the CA3 stratum (s.) radiatum: first, inter-ictal-like discharges that lasted 0.2-1.2 s and had an occurrence rate of 0.3-1.3 Hz; second, ictal-like events (duration: 3-40 s) that occurred at 4-38 x 10(-3) Hz; and third, large-amplitude (up to 8 mV) negative-going potentials that preceded the onset of the ictal-like events and thus appeared to initiate them. 3. None of these synchronous activities was consistently modified by addition of antagonists of the N-methyl-D-aspartate (NMDA) receptor to the ACSF. In contrast, the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 2-10 microM) reversibly blocked interictal- and ictallike discharges. The only synchronous, spontaneous activity recorded in this type of medium consisted of the negative-going potentials that were abolished by the GABAA receptor antagonists bicuculline methiodide (5-20 microM) or picrotoxin (50 microM). Hence they were mediated through the activation of the GABAA receptor. 4. Profile analysis of the 4-AP-induced synchronous activity revealed that the gamma-aminobutyric acid (GABA)-mediated field potential had maximal negative amplitude in s. lacunosum-moleculare, attained equipotentiality at the border between s. radiatum and s. pyramidale, and became positive-going in s. oriens. These findings indicated that the GABA-mediated field potential presumably represented a depolarization occurring in the dendrites of CA3 pyramidal cells. 5. This conclusion was supported by intracellular analysis of the 4-AP-induced activity. The GABA-mediated potential was reflected by a depolarization of the membrane of CA3 pyramidal cells that triggered a few variable-amplitude, fractionated spikes or fast action potentials. By contrast, the ictal-like discharge was associated with a prolonged depolarization during which repetitive bursts of action potentials occurred. Short-lasting depolarizations with bursts of action potentials occurred during each interictal-like discharge. 6. The GABA-mediated potential recorded intracellularly in the presence of CNQX consisted of a prolonged depolarization (up to 12 s) that was still capable of triggering a few fast action potentials and/or fractionated spikes.(ABSTRACT TRUNCATED AT 400 WORDS)

Network Interactions Mediated by New Excitatory Connections Between CA1 Pyramidal Cells in Rats With Kainate-Induced Epilepsy

2002 ◽  
Vol 87 (3) ◽  
pp. 1655-1658 ◽  
Author(s):  
Bret N. Smith ◽  
F. Edward Dudek
Keyword(s):  
Status Epilepticus ◽  
Action Potentials ◽  
Cell Layer ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Ca1 Pyramidal Cells ◽  
Axon Sprouting ◽  
Synaptic Interactions ◽  
Network Bursts ◽  
Ca1 Area

Axon sprouting and synaptic reorganization in the hippocampus are associated with the development of seizures in temporal lobe epilepsy. Synaptic interactions among CA1 pyramidal cells were examined in fragments of hippocampal slices containing only the CA1 area from saline- and kainate-treated rats. Glutamate microapplication to the pyramidal cell layer increased excitatory postsynaptic current (EPSC) frequency, but only in rats with kainate-induced epilepsy. In bicuculline, action potentials evoked in single pyramidal cells increased the frequency of network bursts only in slices from rats with kainate-induced epilepsy. These data further support the hypothesis that excitatory connections between CA1 pyramidal cells increase after kainate-induced status epilepticus.

Partial Disinhibition Is Required for Transition of Stimulus-Induced Sharp Wave–Ripple Complexes Into Recurrent Epileptiform Discharges in Rat Hippocampal Slices

2011 ◽  
Vol 105 (1) ◽  
pp. 172-187 ◽  
Author(s):  
Agustin Liotta ◽  
Gürsel Çalışkan ◽  
Rizwan ul Haq ◽  
Jan O. Hollnagel ◽  
Anton Rösler ◽  
...  
Keyword(s):  
Hippocampal Slices ◽  
Field Potential ◽  
Long Term Potentiation ◽  
Equilibrium Potential ◽  
High Frequency Stimulation ◽  
Extracellular Potassium ◽  
Epileptogenic Zone ◽  
Sharp Wave ◽  
Epileptiform Discharges ◽  
Inhibitory Conductance

Sharp wave–ripple complexes (SPW-Rs) in the intact rodent hippocampus are characterized by slow field potential transients superimposed by close to 200-Hz ripple oscillations. Similar events have been recorded in hippocampal slices where SPW-Rs occur spontaneously or can be induced by repeated application of high-frequency stimulation, a standard protocol for induction of long-lasting long-term potentiation. Such stimulation is reminiscent of protocols used to induce kindling epilepsy and ripple oscillations may be predictive of the epileptogenic zone in temporal lobe epilepsy. In the present study, we investigated the relation between recurrent epileptiform discharges (REDs) and SPW-Rs by studying effects of partial removal of inhibition. In particular, we compared the effects of nicotine, low-dose bicuculline methiodide (BMI), and elevated extracellular potassium concentration ([K+]o) on induced SPW-Rs. We show that nicotine dose-dependently transformed SPW-Rs into REDs. This transition was associated with reduced inhibitory conductance in CA3 pyramidal cells. Similar results were obtained from slices where the GABAergic conductance was reduced by application of low concentrations of BMI (1–2 μM). In contrast, sharp waves were diminished by phenobarbital. Elevating [K+]o from 3 to 8.5 mM did not transform SPW-Rs into REDs but significantly increased their incidence and amplitude. Under these conditions, the equilibrium potential for inhibition was shifted in depolarizing direction, whereas inhibitory conductance was significantly increased. Interestingly, the propensity of elevated [K+]o to induce seizure-like events was reduced in slices where SPW-Rs had been induced. In conclusion, recruitment of inhibitory cells during SPW-Rs may serve as a mechanism by which hyperexcitation and eventually seizure generation might be prevented.

Differential Fall in ATP Accounts for Effects of Temperature on Hypoxic Damage in Rat Hippocampal Slices

2000 ◽  
Vol 83 (6) ◽  
pp. 3462-3472 ◽  
Author(s):  
J. Wang ◽  
G. Chambers ◽  
J. E. Cottrell ◽  
I. S. Kass
Keyword(s):  
Glucose Concentration ◽  
Action Potentials ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Cytosolic Calcium ◽  
Ca1 Neurons ◽  
Ca1 Pyramidal Cells ◽  
Artificial Cerebrospinal Fluid ◽  
Intracellular Ca ◽  
Effects Of Temperature

Intracellular recordings, ATP and cytosolic calcium measurements from CA1 pyramidal cells in rat hippocampal slices were used to examine the mechanisms by which temperature alters hypoxic damage. Hypothermia (34°C) preserved ATP (1.7 vs. 0.8 nM/mg) and improved electrophysiologic recovery of the CA1 neurons after hypoxia; 58% of the neurons subjected to 10 min of hypoxia (34°C) recovered their resting and action potentials, while none of the neurons at 37°C recovered. Increasing the glucose concentration from 4 to 6 mM during normothermic hypoxia improved ATP (1.3 vs. 0.8 nM/mg) and mimicked the effects of hypothermia; 67% of the neurons recovered their resting and action potentials. Hypothermia attenuated the membrane potential changes and the increase in intracellular Ca2+(212 vs. 384 nM) induced by hypoxia. Changing the glucose concentration in the artificial cerebrospinal fluid primarily affects ATP levels during hypoxia. Decreasing the glucose concentration from 4 to 2 mM during hypothermic hypoxia worsened ATP, cytosolic Ca2+, and electrophysiologic recovery. Ten percent of the neurons subjected to 4 min of hypoxia at 40°C recovered their resting and action potentials; this compared with 60% of the neurons subjected to 4 min of normothermic hypoxia. None of the neurons subjected to 10 min of hypoxia at 40°C recovered their resting and action potentials. Hyperthermia (40°C) worsens the electrophysiologic changes and induced a greater increase in intracellular Ca2+(538 vs. 384 nM) during hypoxia. Increasing the glucose concentration from 4 to 8 mM during 10 min of hyperthermic hypoxia improved ATP (1.4 vs. 0.6 nM/mg), Ca2+(267 vs. 538 nM), and electrophysiologic recovery (90 vs. 0%). Our results indicate that the changes in electrophysiologic recovery with temperature are primarily due to changes in ATP and that the changes in depolarization and Ca2+are secondary to these ATP changes. Both primary and secondary changes are important for explaining the improved electrophysiologic recovery with hypothermia.

Local Circuit Abnormalities in Chronically Epileptic Rats After Intrahippocampal Tetanus Toxin Injection in Infancy

1998 ◽  
Vol 79 (1) ◽  
pp. 106-116 ◽  
Author(s):  
Karen L. Smith ◽  
Chong L. Lee ◽  
John W. Swann
Keyword(s):  
Tetanus Toxin ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Membrane Properties ◽  
Small Subset ◽  
Local Circuit ◽  
Epileptiform Discharges ◽  
Network Bursts ◽  
Local Circuits

Smith, Karen L. Chong L. Lee, and John W. Swann. Local circuit abnormalities in chronically epileptic rats after intrahippocampal tetanus toxin injection in infancy. J. Neurophysiol. 79: 106–116, 1998. In vitro slice experiments were undertaken in adult rats to investigate the physiological origins of a chronic epileptic condition that was initiated in infancy. A unilateral injection of a minute quantity of tetanus toxin into hippocampus on postnatal day 10 produced a severe convulsive syndrome characterized by brief but repeated seizures that lasted for 5–7 days. Hippocampal slices were then taken from these rats in adulthood because at this time previous studies have shown the occurrence of electrographic and behavioral seizures. Dramatic alterations in local circuit functioning were observed. In normal artificial cerebrospinal fluid (ACSF), spontaneous epileptiform network bursts were recorded in a majority (73%) of experimental rats. Network bursts occurred in area CA3of both the injected and contralateral hippocampus. These consisted of intracellular depolarization shifts that were coincident with extracellularly recorded network bursts. Often they occurred at frequencies of 0.05–0.1 Hz and although variable in amplitude and duration, had all-or-none-like qualities. These events appeared to arise largely from local circuits in the CA3Csubfield. Network bursts were rarely recorded in area CA1and were never observed in the dentate gyrus. However in 31% of rats, a novel, higher frequency (2–8 Hz) field potential was recorded in area CA1. This was coincident with rhythmic, intracellularly recorded, inhibitory postsynaptic potentials (IPSPs). These summated IPSPs blocked action potential firing and reversed polarity near −75 mV. To understand the origins of network bursting in area CA3C, comparisons were made of the fundamental neurophysiological properties of pyramidal cells in epileptic and control rats. Of the passive and active membrane properties examined, all appeared normal. Unusually prolonged bursts of action potentials were observed in a small subset of pyramidal cells. However on average the duration of intrinsic bursts were unaltered in the CA3 neurons analyzed from experimental rats. To explore the role that alterations in CA3recurrent excitatory network excitability may play in epileptiform discharges, picrotoxin was bath applied. On blockade of γ-aminobutyric acid (GABAA) receptors, slices from experimental rats underwent prolonged electrographic seizures that were up to 10 s in duration. In contrast, slices from control rats produced only brief 100-ms network bursts. These results suggest that a change in excitability within CA3Crecurrent excitatory networks likely contributes to seizures in chronically epileptic rats. However, at the same time, this hyperexcitability is controlled to an important degree by functional GABAA-mediated synaptic inhibition.

Ionic Mechanisms of Spontaneous GABAergic Events in Rat Hippocampal Slices Exposed to 4-Aminopyridine

1997 ◽  
Vol 78 (5) ◽  
pp. 2582-2591 ◽  
Author(s):  
Karri Lamsa ◽  
Kai Kaila
Keyword(s):  
Pyramidal Cell ◽  
Cell Response ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Fold Increase ◽  
Stratum Radiatum ◽  
Intracellular Recordings ◽  
Free Medium ◽  
Ionic Mechanisms

Lamsa, Karri and Kai Kaila. Ionic mechanisms of spontaneous GABAergic events in rat hippocampal slices exposed to 4-aminopyridine. J. Neurophysiol. 78: 2582–2591, 1997. Ion-selective (H+ and K+) microelectrode techniques as well as conventional extra- and intracellular recordings were used to study the ionic mechanisms of propagating spontaneous GABAergic events (SGEs) in rat hippocampal slices exposed to 4-aminopyridine (4-AP, 50–100 μM). All experiments were made in the presence of antagonists of ionotropic glutamate receptors [10 μM 6-nitro-7-sulphamoylbenzoquinoxaline-2,3-dione (NBQX) and 40 μM dl-2-amino-5-phosphonopentanoic acid (AP5)]. The SGEs were composed of a negative-going change in field potential with a temporally coincident increase (0.7 ± 0.3 mM; mean ± SE) in extracellular K+ ([K+]o) and an alkaline transient (0.01–0.08 units) in extracellular pH (pHo) in stratum radiatum of the area CA1. Simultaneous intracellular recordings showed a triphasic hyperpolarization-depolarization–late hyperpolarization response in pyramidal cells. Application of pentobarbital sodium (PB, 100 μM) decreased the interval between SGEs from a mean value of 35 to ∼20 s and shortened the period of refractoriness of stimulus-evoked propagating events. This was accompanied by an increase in the amplitude of the field potential response of the [K+]o and the pHo shifts and of the depolarizing phase of the pyramidal-cell response. The SGEs were completely blocked by the γ-aminobutyric acid-A (GABAA) receptor antagonist, picrotoxin (PiTX; 100 μM). The amplitudes of the negative-going field potential and of the depolarizing phase of the pyramidal-cell response as well as the ionic shifts associated with SGEs were strongly suppressed in the nominal absence of CO2/HCO− 3. There was a five-fold increase in the interevent interval, and propagating SGEs could not be evoked by stimuli given at intervals shorter than ∼2–3 min. Exposure to inhibitors of carbonic anhydrase, benzolamide (BA; 10 μM) or ethoxyzolamide (EZA; 50 μM) fully blocked the alkaline pHo transients and turned them into acid shifts. The poorly membrane-permeant BA had no discernible effect on the other components of the SGEs, but application of EZA had effects reminiscent to those of CO2/HCO− 3-free medium. Addition of the GABAA receptor–permeant weak-acid anion, formate (20 mM) reestablished the SGEs that were first suppressed by exposure to the CO2/HCO− 3-free medium. No SGEs were seen in the presence of a similar concentration of the GABAA receptor–impermeant anion propionate. Unlike the alkaline transients associated with HCO− 3-driven SGEs, those supported by formate were not blocked by BA. The present data suggest that an inward current carried by bicarbonate is necessary for the generation of SGEs and that the GABAA receptor–mediated excitatory coupling among GABAergic interneurons is essentially dependent on the availability of intracellular bicarbonate.

Level of Arousal During the Small Irregular Activity State in the Rat Hippocampal EEG

2004 ◽  
Vol 91 (6) ◽  
pp. 2649-2657 ◽  
Author(s):  
Beata Jarosiewicz ◽  
William E. Skaggs
Keyword(s):  
Slow Wave Sleep ◽  
Power Spectra ◽  
Pyramidal Cells ◽  
Auditory Stimuli ◽  
Sleep State ◽  
Population Activity ◽  
Ca1 Pyramidal Cells ◽  
Emg Amplitude ◽  
Current Location ◽  
Activity State

The sleeping rat cycles between two well-characterized hippocampal physiological states, large irregular activity (LIA) during slow-wave sleep (SWS) and theta activity during rapid-eye-movement sleep (REM). A third, less well-characterized electroencephalographic (EEG) state, termed “small irregular activity” (SIA), has been reported to occur when an animal is startled out of sleep without moving and during active waking when it abruptly freezes. We recently found that the hippocampal population activity of a spontaneous sleep state whose EEG resembles SIA reflects the rat's current location in space, suggesting that it is also a state of heightened arousal. To test whether this spontaneous SIA state corresponds to the SIA state reported in the literature and to compare the level of arousal during SIA to the other well-characterized physiological states, we recorded unit activity from ensembles of hippocampal CA1 pyramidal cells, EEG from the hippocampus and the neocortex, and electromyography (EMG) from the dorsal neck musculature in rats presented with auditory stimuli while foraging for randomly scattered food pellets and while sleeping. Auditory stimuli presented during sleep reliably induced SIA episodes very similar to spontaneous SIA in hippocampal and neocortical EEG amplitudes and power spectra, EMG amplitude, and CA1 population activity. Both spontaneous and elicited SIA exhibited neocortical desynchronization, and both had EMG amplitude comparable to that of waking LIA. We conclude based on this and other evidence that spontaneous SIA and elicited SIA correspond to a single state and that the level of arousal in SIA is higher than in the well-characterized sleep states but lower than the active theta state.

scholarly journals Zinc Enhances the Inhibitory Effects of Strychnine-Sensitive Glycine Receptors in Mouse Hippocampal Neurons

2007 ◽  
Vol 98 (6) ◽  
pp. 3666-3676 ◽  
Author(s):  
Hai Xia Zhang ◽  
Liu Lin Thio
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Hippocampal Neurons ◽  
Neuronal Excitability ◽  
Hippocampal Slices ◽  
Glycine Receptors ◽  
Inhibitory Effects ◽  
Action Potential Firing ◽  
Embryonic Mouse ◽  
Potential Firing

Although extracellular Zn2+ is an endogenous biphasic modulator of strychnine-sensitive glycine receptors (GlyRs), the physiological significance of this modulation remains poorly understood. Zn2+ modulation of GlyR may be especially important in the hippocampus where presynaptic Zn2+ is abundant. Using cultured embryonic mouse hippocampal neurons, we examined whether 1 μM Zn2+, a potentiating concentration, enhances the inhibitory effects of GlyRs activated by sustained glycine applications. Sustained 20 μM glycine (EC25) applications alone did not decrease the number of action potentials evoked by depolarizing steps, but they did in 1 μM Zn2+. At least part of this effect resulted from Zn2+ enhancing the GlyR-induced decrease in input resistance. Sustained 20 μM glycine applications alone did not alter neuronal bursting, a form of hyperexcitability induced by omitting extracellular Mg2+. However, sustained 20 μM glycine applications depressed neuronal bursting in 1 μM Zn2+. Zn2+ did not enhance the inhibitory effects of sustained 60 μM glycine (EC70) applications in these paradigms. These results suggest that tonic GlyR activation could decrease neuronal excitability. To test this possibility, we examined the effect of the GlyR antagonist strychnine and the Zn2+ chelator tricine on action potential firing by CA1 pyramidal neurons in mouse hippocampal slices. Co-applying strychnine and tricine slightly but significantly increased the number of action potentials fired during a depolarizing current step and decreased the rheobase for action potential firing. Thus Zn2+ may modulate neuronal excitability normally and in pathological conditions such as seizures by potentiating GlyRs tonically activated by low agonist concentrations.

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