Blockade Of Synaptic Inhibition Research Articles

A New Micro-holder Device for Local Drug Delivery during In Vivo Whole-cell Recordings

Focal administration of pharmacological agents during in vivo recordings is a useful technique to study the functional properties of neural microcircuits. However, the lack of visual control makes this task difficult and inaccurate, especially when targeting small and deep regions where spillover to neighboring regions is likely to occur. An additional problem with recording stability arises when combining focal drug administration with in vivo intracellular recordings, which are highly sensitive to mechanical vibrations. To address these technical issues, we designed a micro-holder that enables accurate local application of pharmacological agents during in vivo whole-cell recordings. The holder couples the recording and drug delivery pipettes with adjustable distance between the respective tips adapted to the experimental needs. To test the efficacy of the micro-holder we first performed whole-cell recordings in mouse primary somatosensory cortex (S1) with simultaneous extracellular recordings in S1 and motor cortex (M1), before and after local application of bicuculline methiodide (BMI 200 µM). The blockade of synaptic inhibition resulted in increased amplitudes and rising slopes of “Up states”, and shortening of their duration. We then checked the usability of the micro-holder in a deeper brain structure, the striatum. We applied tetrodotoxin (TTX 10 µM) during whole-cell recordings in the striatum, while simultaneously obtaining extracellular recordings in S1 and M1. The focal application of TTX in the striatum blocked Up states in the recorded striatal neurons, without affecting the cortical activity. We also describe two different approaches for precisely releasing the drugs without unwanted leakage along the pipette approach trajectory.

Chapter 1 - Rhythmic Bursting in the Pre-Bötzinger Complex: Mechanisms and Models

The pre-Bötzinger complex (pre-BötC), a neural structure involved in respiratory rhythm generation, can generate rhythmic bursting activity in vitro that persists after blockade of synaptic inhibition. Experimental studies have identified two mechanisms potentially involved in this activity: one based on the persistent sodium current (INaP) and the other involving calcium (ICa) and/or calcium-activated nonspecific cation (ICAN) currents. In this modeling study, we investigated bursting generated in single neurons and excitatory neural populations with randomly distributed conductances of INaP and ICa. We analyzed the possible roles of these currents, the Na(+)/K(+) pump, synaptic mechanisms, and network interactions in rhythmic bursting generated under different conditions. We show that a population of synaptically coupled excitatory neurons with randomly distributed INaP- and/or ICAN-mediated burst generating mechanisms can operate in different oscillatory regimes with bursting dependent on either current or independent of both. The existence of multiple oscillatory regimes and their state dependence may explain rhythmic activities observed in the pre-BötC under different conditions.

Sodium and calcium mechanisms of rhythmic bursting in excitatory neural networks of the pre-Bötzinger complex: a computational modelling study.

The neural mechanisms generating rhythmic bursting activity in the mammalian brainstem, particularly in the pre-Bötzinger complex (pre-BötC), which is involved in respiratory rhythm generation, and in the spinal cord (e.g. locomotor rhythmic activity) that persist after blockade of synaptic inhibition remain poorly understood. Experimental studies in rodent medullary slices containing the pre-BötC identified two mechanisms that could potentially contribute to the generation of rhythmic bursting: one based on the persistent Na(+) current (I(NaP)), and the other involving the voltage-gated Ca(2+) current (I(Ca)) and the Ca(2+) -activated nonspecific cation current (I(CAN)), activated by intracellular Ca(2+) accumulated from extracellular and intracellular sources. However, the involvement and relative roles of these mechanisms in rhythmic bursting are still under debate. In this theoretical/modelling study, we investigated Na(+)-dependent and Ca(2+)-dependent bursting generated in single cells and heterogeneous populations of synaptically interconnected excitatory neurons with I(NaP) and I(Ca) randomly distributed within populations. We analysed the possible roles of network connections, ionotropic and metabotropic synaptic mechanisms, intracellular Ca(2+) release, and the Na(+)/K(+) pump in rhythmic bursting generated under different conditions. We show that a heterogeneous population of excitatory neurons can operate in different oscillatory regimes with bursting dependent on I(NaP) and/or I(CAN), or independent of both. We demonstrate that the operating bursting mechanism may depend on neuronal excitation, synaptic interactions within the network, and the relative expression of particular ionic currents. The existence of multiple oscillatory regimes and their state dependence demonstrated in our models may explain different rhythmic activities observed in the pre-BötC and other brainstem/spinal cord circuits under different experimental conditions.

Modeling Na+- and Ca2+-dependent mechanisms of rhythmic bursting in excitatory neural networks

The mechanisms generating neural oscillations in the mammalian brainstem, particularly in the pre-Botzinger complex (pre-BotC) involved in control of respiration, and the spinal cord (e.g. circuits controlling locomotion) that persist after blockade of synaptic inhibition, remain poorly understood. Experimental studies in medullary slices from neonatal rodents containing the pre-BotC identified two mechanisms that could potentially contribute to generation of rhythmic bursting in the pre-BotC: one based on the persistent sodium current (INaP) [1,2], and the other involving the voltage-gated calcium (ICa) [3] and/or the calcium-activated nonspecific cation current (ICAN), activated by intracellular Ca2+ accumulated from extra- and/or intracellular sources [4]. However, the involvement and relative roles of these mechanisms in rhythmic bursting are still under debate. In this theoretical/modeling study we investigated Na+- and Ca2+-dependent bursting generated in single cells and in a heterogeneous population of synaptically interconnected excitatory neurons with INaP, and ICa randomly distributed within the population. We analyzed the possible roles of network connections, ionotropic and metabotropic synaptic mechanisms, intracellular Ca2+ release, and the Na+/K+ pump in rhythmic bursting activity generated under different conditions. We show that the heterogeneous population of excitatory neurons can operate in different oscillatory regimes with bursting dependent on INaP and/or ICAN, or independent of both (Fig. ​(Fig.1).1). The oscillatory regime and operating bursting mechanism may depend on neuronal excitability, synaptic interactions and relative expression of particular ionic currents. Figure 1 A map of bursting activities derived from multiple simulations of the excitatory neuron population and presented in a 2D parameter space (gtonic, ), where gtonic is the external excitatory drive to all neurons, N is the number of neurons in the population, ... The existence of multiple oscillatory regimes and their state-dependency may provide explanations for different rhythmic activities observed in the brainstem and spinal cord under different experimental conditions.

Interaural Time Difference Processing in the Mammalian Medial Superior Olive: The Role of Glycinergic Inhibition

The dominant cue for localization of low-frequency sounds are microsecond differences in the time-of-arrival of sounds at the two ears [interaural time difference (ITD)]. In mammals, ITD sensitivity is established in the medial superior olive (MSO) by coincidence detection of excitatory inputs from both ears. Hence the relative delay of the binaural inputs is crucial for adjusting ITD sensitivity in MSO cells. How these delays are constructed is, however, still unknown. Specifically, the question of whether inhibitory inputs are involved in timing the net excitation in MSO cells, and if so how, is controversial. These inhibitory inputs derive from the nuclei of the trapezoid body, which have physiological and structural specializations for high-fidelity temporal transmission, raising the possibility that well timed inhibition is involved in tuning ITD sensitivity. Here, we present physiological and pharmacological data from in vivo extracellular MSO recordings in anesthetized gerbils. Reversible blockade of synaptic inhibition by iontophoretic application of the glycine antagonist strychnine increased firing rates and significantly shifted ITD sensitivity of MSO neurons. This indicates that glycinergic inhibition plays a major role in tuning the delays of binaural excitation. We also tonically applied glycine, which lowered firing rates but also shifted ITD sensitivity in a way analogous to strychnine. Hence tonic glycine application experimentally decoupled the effect of inhibition from the timing of its inputs. We conclude that, for proper ITD processing, not only is inhibition necessary, but it must also be precisely timed.

Associating synaptic and intrinsic plasticity

Associating synaptic and intrinsic plasticity

Interaural time difference processing in the mammalian medial superior olive

The dominant cue for localization of low-frequency sounds are microsecond differences in the time-of-arrival of sounds at the two ears [interaural time difference (ITD)]. In mammals, ITD sensitivity is established in the medial superior olive (MSO) by coincidence detection of excitatory inputs from both ears. Hence the relative delay of the binaural inputs is crucial for adjusting ITD sensitivity in MSO cells. How these delays are constructed is, however, still unknown. Specifically, the question of whether inhibitory inputs are involved in timing the net excitation in MSO cells, and if so how, is controversial. These inhibitory inputs derive from the nuclei of the trapezoid body, which have physiological and structural specializations for high-fidelity temporal transmission, raising the possibility that well timed inhibition is involved in tuning ITD sensitivity. Here, we present physiological and pharmacological data from in vivo extracellular MSO recordings in anesthetized gerbils. Reversible blockade of synaptic inhibition by iontophoretic application of the glycine antagonist strychnine increased firing rates and significantly shifted ITD sensitivity of MSO neurons. This indicates that glycinergic inhibition plays a major role in tuning the delays of binaural excitation. We also tonically applied glycine, which lowered firing rates but also shifted ITD sensitivity in a way analogous to strychnine. Hence tonic glycine application experimentally decoupled the effect of inhibition from the timing of its inputs. We conclude that, for proper ITD processing, not only is inhibition necessary, but it must also be precisely timed.

Rebuttal from Ramirez

Rebuttal from Ramirez

Propriospinal Circuitry Underlying Interlimb Coordination in Mammalian Quadrupedal Locomotion

Soon after birth, freely moving quadrupeds can express locomotor activity with coordinated forelimb and hindlimb movements. To investigate the neural mechanisms underlying this coordination, we used an isolated spinal cord preparation from neonatal rats. Under bath-applied 5-HT, N-methyl-d,l-aspartate (NMA), and dopamine (DA), the isolated cord generates fictive locomotion in which homolateral cervicolumbar extensor motor bursts occur in phase opposition, as does bursting in homologous (left-right) extensor motoneurons. This coordination corresponded to a walking gait monitored with EMG recordings in the freely behaving animal. Functional decoupling of the cervical and lumbar generators in vitro by sucrose blockade at the thoracic cord level revealed independent rhythmogenic capabilities with similar cycle frequencies in the two locomotor regions. When the cord was partitioned at different thoracic levels and 5-HT/NMA/DA was applied to the more caudal compartment, the ability of the lumbar generators to drive their cervical counterparts increased with the proportion of chemically exposed thoracic segments. Blockade of synaptic inhibition at the lumbar level caused synchronous bilateral lumbar rhythmicity that, surprisingly, also was able to impose bilaterally synchronous bursting at the unblocked cervical level. Furthermore, after a midsagittal section from spinal segments C1 to T7, and during additional blockade of cervical synaptic inhibition, the cord exposed to 5-HT/NMA/DA continued to produce a coordinated fictive walking pattern similar to that observed in control. Thus, in the newborn rat, a caudorostral propriospinal excitability gradient appears to mediate interlimb coordination, which relies more on asymmetric axial connectivity (both excitatory and inhibitory) between the lumbar and cervical generators than on differences in their inherent rhythmogenic capacities.

Blockade of synaptic inhibition within the pre-Bötzinger complex in the cat suppresses respiratory rhythm generation in vivo.

1. The role of synaptic inhibition in respiratory rhythm generation was analysed by microinjections of GABAA and glycine receptor antagonists into the bilateral pre-Botzinger complex (PBC) of anaesthetized cats. Central respiratory activity was monitored by phrenic nerve recordings. 2. Bilateral injections of bicuculline (50 or 100 microM) irreversibly slowed respiratory frequency and induced apneustic patterns. 3. Bilateral injections of strychnine (50 or 100 microM) greatly reduced phrenic burst amplitudes leading to increased burst frequency or irreversibly blocked rhythmic phrenic discharges. After unilateral tetrodotoxin (TTX) blockade in the PBC, strychnine injection into the contralateral PBC blocked rhythmic phrenic discharges. 4. Bilateral blockade of both GABAergic and glycinergic inhibition abolished rhythmic burst discharges and only tonic phrenic activity remained. Such tonic activity was blocked only by TTX (1 microM). 5. Potentiation of synaptic inhibition by the serotonin 1A receptor agonist 8-hydroxydipropylaminotetralin (8-OH-DPAT; 50 microM) restored rhythmic activity only when given shortly after strychnine and bicuculline applications. It was, however, ineffective after blockade of synaptic inhibition was complete. 6. The study demonstrates the significance of synaptic inhibition in the process of respiratory generation in the adult cat in vivo.

Multiple metabotropic glutamate receptors regulate hippocampal function.

Selective activation of metabotropic glutamate receptors with trans-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD) stimulates phosphoinositide hydrolysis and elicits three major physiological responses in area CA1 of the hippocampus. These include direct excitation of pyramidal cells, blockade of synaptic inhibition, and decreased transmission at the Schaffer collateral-CA1 pyramidal cell synapse. Physiological effects of trans-ACPD are thought to be mediated by activation of phosphoinositide hydrolysis. However, it is now clear that multiple metabotropic glutamate receptor subtypes exist, some of which are not coupled to phosphoinositide hydrolysis. Thus, we performed a series of studies aimed at determining whether the physiological effects of trans-ACPD in the hippocampus are mediated by activation of the predominant phosphoinositide hydrolysis-linked glutamate-receptor. We report that L-2-amino-3-phosphonopropionic acid (L-AP3), an antagonist of trans-ACPD-stimulated phosphoinositide hydrolysis, does not inhibit the physiological effects of trans-ACPD in area CA1 at concentrations that maximally inhibit trans-ACPD-stimulated phosphoinositide hydrolysis in this region. Furthermore, 1S,3S-ACPD activates the phosphoinositide hydrolysis-linked glutamate receptor but does not reduce evoked field excitatory postsynaptic potentials (EPSPs) in area CA1. However, we report that the physiological effects of 1R,3S- and 1S,3R-ACPD are consistent with the hypothesis that these effects are mediated by activation of a metabotropic glutamate receptor. Thus, our data are consistent with the hypothesis that the physiological effects of trans-ACPD in area CA1 of the hippocampus are mediated by metabotropic glutamate receptors that are distinct from the AP3-sensitive phosphoinositide hydrolysis-linked glutamate receptor.

Excitatory effects of ACPD receptor activation in the hippocampus are mediated by direct effects on pyramidal cells and blockade of synaptic inhibition.

1. Phosphoinositide hydrolysis-linked excitatory amino acid (EAA) receptors (ACPD receptors) are selectively activated by the glutamate analogue trans-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD). Regional analysis of trans-ACPD-induced phosphoinositide hydrolysis indicates that this response is greater in the hippocampus than in other brain regions. Therefore we designed a series of studies aimed at testing the hypothesis that activation of this receptor modulates synaptic function in the hippocampal region. 2. We report that trans-ACPD dramatically altered field population spikes at each of the three major synapses in the hippocampal trisynaptic circuit at concentrations that are effective in activating phosphoinositide hydrolysis. At the perforant path-dentate gyrus synapse, bath application of trans-ACPD resulted in a decrease in the amplitude of field population spikes. In contrast, trans-ACPD markedly enhanced field population spike amplitude at the mossy fiber-CA3 synapse and the Schaffer collateral-CA1 synapse. In area CA1, but not area CA3, trans-ACPD also induced generation of multiple population spikes. 3. Simultaneous field potential recordings from the s. pyramidale and s. radiatum in area CA1 revealed that the effect of trans-ACPD on population spikes in this region was not accompanied by an increase in the initial slope of the field EPSP. This suggests that the effect of trans-ACPD was not mediated by a presynaptic action but must be mediated by direct effects on CA1 pyramidal cells or by a decrease in synaptic inhibition. 4. trans-ACPD had a number of direct excitatory effects on CA1 pyramidal cells. These included 1) cell depolarization (with an increase in input resistance), 2) inhibition of the slow afterhyperpolarization, and 3) blockade of spike frequency adaptation. trans-ACPD also had effects on CA1 pyramidal cells that were not excitatory in nature. These included an increase in the threshold for initiation of calcium spikes and an increase in interspike interval during prolonged current injection. None of these effects were mimicked by an ACPD analogue that does not activate the ACPD receptor (trans-methanoglutamate), nor were they blocked by kynurenate, a nonselective EAA receptor antagonist that does not block the ACPD receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

Chronic epileptic foci in neocortex: in vivo and in vitro effects of tetanus toxin.

Injection of 0.2 - 3.0 ng of tetanus toxin into rat parietal neocortex resulted in permanent (> 7 months) changes in the local circuit properties of this tissue. It caused excessive synchronization of neuronal activity. This was seen as spontaneous paroxysmal field potentials and/or evoked all-or-none population burst discharges. Such activity was recorded widely over the parietal and temporal areas of both the injected and the contralateral hemispheres from as little as 16 h after injection up to the maximum survival time of 7 months. Several observations suggest that the speed with which the hypersynchronous activity spread to the opposite hemisphere reflects transport of the toxin through corticocortical axons, and consequent blockade of synaptic inhibition. However, from what is known of the half life of the peptide in brain, it is unlikely that the persistent, widespread distribution of epileptiform discharge several months after injection was due to the continued presence of toxin. Thus, intracortical application of tetanus toxin provides a good experimental model of chronic focal epilepsies, and raises fundamental questions regarding the long term regulation of local circuit properties in the neocortex.

Background firing in cortical neurons with blockade of synaptic inhibition in guinea pig neocortical slices maintained in vitro

The effects of 100 µM picrotoxin on neuronal background firing were investigated in guinea pig neocortical slices maintained in vitro. Picrotoxin or bicuculline application is known to bring about an abrupt increase in background firing or the onset of spontaneous epileptiform volleys at a higher excitatory and inhibitory level in the in vivo than in the in vitro cortex. Blocking GABA-ergic inhibition hardly affected the pattern of background spike trains, although stimuli-induced response did become epileptiform. Findings from this research would thus indicate that any inhibitory processes taking place during in vitro background activity are only very slight and exert no significant effect on this activity.

Sodium valproate decreases synaptic potentiation and epileptiform activity in hippocampus

The actions of sodium valproate (NaVP) were studied in the in vitro hippocampus using extracellular, intracellular and voltage-clamp recording techniques. In the CA1 region, concentrations of 30–200 μM NaVP reduced the amplitude but not the time course of post-tetanic potentiation (PTP) of dendritic field excitatory postsynaptic potentials (EPSPs). Epileptiform discharges were studied intracellularly in CA3 cells after pharmacological blockade of synaptic inhibition and repeated tetanic stimulation. NaVP (100 μM) blocked evoked paroxysmal depolarizing shift (PDS) discharges through a mechanism of increasing the threshold for burst-firing. When the PDS current was studied under voltage-clamp, application of NaVP (100 μM) resulted in a graded reduction of the PDS waveform. All of the actions of NaVP may result from inhibition of excitatory synaptic transmission following repetitive cell firing. A hypothesis is proposed that NaVP may act to decrease excitatory synaptic potentiation necessary for network synchronization.

Synchronized afterdischarges in the hippocampus: Simulation studies of the cellular mechanism

Synchronized multiple bursts represent an epileptic neuronal behavior transitional between synchronized single bursts (interictal spikes) and self-sustained seizures. As described in the previous paper, synchronized multiple bursts occur in hippocampal slices treated with picrotoxin. Multiple bursts consist of an initial prolonged depolarizing burst followed by a rhythmical series of afterdischarges. Both the initial burst and the afterdischarges are synaptically elicited. Our previously described model of the interictal spike illustrates that the generation of a single synchronized burst requires a neuronal network possessing the following properties: intrinsic bursting capability of individual neurons, the presence of recurrent excitatory connections between principal neurons and the blockade of synaptic inhibition. The model demonstrates that the generation of single synchronized bursts involves the initial excitation of one or more neurons, and the subsequent sequential spread of excitation through a population of neurons via recurrent excitatory synapses. In the present study, we examined whether this same mechanism assumed in the previous model could also allow for the generation of synchronized afterdischarges in a population of neurons. We tested the effects of manipulating three network factors: synaptic strength, synaptic density and the refractoriness in the population members following a period of excitation. We discovered that the refractory period following prolonged excitation assumed in our previous model was insufficient to allow for afterdischarge generation. Once sufficient refractoriness was introduced, afterdischarges appeared in our network of neurons. In the present study, the required refractoriness was attributed to the properties of pyramidal cell axons. In principle, such refractoriness might be located elsewhere in the network. The possible contribution of axonal properties is emphasized because of the known intermittent conduction in other axons. Our present model also reproduced other experimental data. Thus, if the network was too small or if synaptic strength was too small, then only a single synchronized burst occurred. The basic assumptions of this model are both biologically plausible and experimentally testable.

Self-excitation of olfactory bulb neurones.

The concept that neurotransmitter released from a neurone may feed back and influence the excitability of the same neurone has been suggested by a variety of evidence. Anatomical studies have shown that axon collaterals can arborize among the dendrites of the parent neurone1–7, suggesting a direct feedback via axon collaterals. In addition, the dendritic release of dopamine from substantia nigra neurones has suggested that dopamine may exert a direct feedback inhibition of these neurones8,9. Little electrophysiological evidence is available, however, to indicate that such a mechanism does exist. Based on intracellular recordings, Park et al.10 have proposed a direct inhibitory feedback in the neostriatum, but a presynaptic mechanism was not entirely excluded. We have now found that blockade of synaptic inhibition of relay neurones in the olfactory bulb unmasks long-lasting depolarizing potentials which can trigger repetitive discharges. These depolarizing potentials result from direct feedback of dendritically released excitatory transmitter onto the same and neighbouring relay neurones. Such a process might contribute to epileptogenic neuronal discharge.

Blockade of synaptic inhibition reveals long-lasting synaptic excitation in isolated turtle olfactory bulb.

Blockade of synaptic inhibition reveals long-lasting synaptic excitation in isolated turtle olfactory bulb.M C Nowycky, K Mori, and G M ShepherdM C Nowycky, K Mori, and G M ShepherdPublished Online:01 Sep 1981https://doi.org/10.1152/jn.1981.46.3.649MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformationCited ByOdor-Induced Persistent Discharge of Mitral Cells in the Mouse Olfactory BulbHideyuki Matsumoto, Hideki Kashiwadani, Hiroshi Nagao, Atsu Aiba, and Kensaku Mori1 April 2009 | Journal of Neurophysiology, Vol. 101, No. 4Reciprocal intraglomerular excitation and intra- and interglomerular lateral inhibition between mouse olfactory bulb mitral cells22 July 2004 | The Journal of Physiology, Vol. 542, No. 2Emerging rules for the distributions of active dendritic conductances1 May 2002 | Nature Reviews Neuroscience, Vol. 3, No. 5Spatio-Temporal Dynamics of Odor Representations in the Mammalian Olfactory BulbNeuron, Vol. 34, No. 2Odour-evoked [Ca 2+ ] transients in mitral cell dendrites of frog olfactory glomeruli20 December 2001 | European Journal of Neuroscience, Vol. 13, No. 9Dendritic Glutamate Autoreceptors Modulate Signal Processing in Rat Mitral CellsPaul-Antoine Salin, Pierre-Marie Lledo, Jean-Didier Vincent, and Serge Charpak1 March 2001 | Journal of Neurophysiology, Vol. 85, No. 3Functional Role of NMDA Autoreceptors in Olfactory Mitral CellsDaniel Friedman, and Ben W. Strowbridge1 July 2000 | Journal of Neurophysiology, Vol. 84, No. 1Computation of frequency-to-spatial transform by olfactory bulb glomeruliBiological Cybernetics, Vol. 65, No. 5Large mechanical changes in the bullfrog olfactory bulb evoked by afferent fiber stimulationBrain Research, Vol. 475, No. 1Membrane and synaptic properties of identified neurons in the olfactory bulbProgress in Neurobiology, Vol. 29, No. 3Petit mal seizure spikes in olfactory bulb and cortex caused by runaway inhibition after exhaustion of excitationBrain Research Reviews, Vol. 11, No. 3Intracellular potentials of salamander mitral/tufted neurons in response to odor stimulationBrain Research, Vol. 338, No. 1Periglomerular cell action on mitral cells in olfactory bulb shown by current source density analysisBrain Research, Vol. 308, No. 2Neurochemistry of the vertebrate olfactory bulbNeuroscience, Vol. 10, No. 3An electrophysiological study of the accessory olfactory bulb in the rabbit—I. Analysis of electrically evoked potential fieldsNeuroscience, Vol. 10, No. 1An electrophysiological study of the accessory olfactory bulb in the rabbit—II. Input-output relations as assessed from analysis of intra- and extracellular unit recordingsNeuroscience, Vol. 10, No. 1Evoked field potential analysis of dopaminergic mechanisms in the isolated turtle olfactory bulbNeuroscience, Vol. 8, No. 4 More from this issue > Volume 46Issue 3September 1981Pages 649-58 https://doi.org/10.1152/jn.1981.46.3.649PubMed7299439History Published online 1 September 1981 Published in print 1 September 1981 Metrics

Epileptiform burst afterhyperolarization: calcium-dependent potassium potential in hippocampal CA1 pyramidal cells.

Synaptic excitation of hippocampal cells during blockade of synaptic inhibition results in an epileptiform "burst" potential followed by a prolonged afterhyperpolarization. This afterhyperpolarization resembles the one that is seen after the epileptic interictal spike and that is considered of critical importance in preventing seizure development. The afterhyperpolarization produced in the presence of y-aminobutyric acid antagonists is associated with a conductance increase and is inhibitory. It can occur in an all-or-none fashion after a burst, is independent of chloride, and is depressed by barium. The afterhyperpolarization has a reversal potential of (-86) millivolts, and the reversal potential is strongly dependent on the extracellular concentration of potassium. The afterhyperpolarization appears to be an intrinsic, inhibitory potassium potential mediated by calcium. This finding has implications for understanding the cellular mechanisms of epilepsy.