Field Potential Responses Research Articles

Climbing fiber responses evoked in lobule VII of the posterior cerebellum from a vagal nerve in rabbits

The vagal afferent projection to the cerebellar posterior lobe was examined in decerebrate rabbits with electrophysiological techniques. Electrical stimulation of a vagal nerve at the cervical region evoked field potential responses on both sides of the posterior vermal cortex from lobule VI to VIII. The most prominent potentials appeared in the ipsilateral medial vermis of lobule VIIa. These potentials had a latency of 15.6 ms, and were negative in the molecular layer and positive in the granular layer. At a stimulation rate of 20 Hz, their amplitude was reduced by 70% of the control value at 1 Hz. Superimposed on these field potentials, unitary complex spikes were recorded at the depths of Purkinje cell layers. These results indicate that the medial vermal cortex of lobule VII receives vagal afferent signals via climbing fibers, which presumably convey cardiovascular information.

Modification by focused ultrasound pulses of electrically evoked responses from an in vitro hippocampal preparation

The application of short pulses of focused ultrasound was studied as a method of modifying electrically evoked responses in the mammalian brain. The in vitro hippocampal preparation was employed to facilitate delivery and dosimetry of ultrasound, and assessment of mechanisms of ultrasound effects. Cellular and dendritic field potential responses evoked by electrical stimulation of the Schaffer/Commissural afferents were examined before, during and after exposure of a portion of the CA1 region to focused ultrasound pulses for periods ranging from 2 to 15 min. Focused ultrasound with a repetition rate of 150 kHz was delivered in pulses comparable in duration to an electrical pulse that could initiate activity in the nervous system. The pulses had a center frequency of 750 kHz, durations of about 6 μs, and spatial-peak-temporal-averaged intensities of about 80 W/cm 2. These parameters are markedly different from those employed in conventional diagnostic ultrasound. Temperatures in the bath and tissue were monitored. Extracellular field potentials reflecting the presynaptic fiber volley, dendritic response and cellular discharge were significantly reduced by exposure to ultrasound. Recovery occurred to varying degrees, and in one experiment was complete. Average temperature changes observed were less than 1 °C. The present study demonstrates that the electrically evoked response in mammalian brain can be altered by ultrasound in a non-thermal, non-cavitational mode, and that such effects are potentially reversible.

Excitatory amino acid receptor-channels in Purkinje cells in thin cerebellar slices

Glutamate receptors of the N-methyl-D-aspartate (NMDA) and non-NMDA type serve different functions during excitatory synaptic transmission. Although many central neurons bear both types of receptor, the evidence concerning the sensitivity of cerebellar Purkinje cells to NMDA is contradictory. To investigate the receptor types present in Purkinje cells, we have used whole-cell and outside-out patch-clamp methods to record from cells in thin cerebellar slices from young rats. At a holding potential of -70 mV (in nominally Mg(2+)-free medium, with added glycine) NMDA caused a whole-cell current response which consisted of a dramatic increase in the frequency of synaptic currents. In the presence of tetrodotoxin (TTX) and the gamma-aminobutyric acidA (GABAA) receptor antagonist bicuculline, spontaneous synaptic currents and responses to NMDA were inhibited. In a proportion of cells a small polysynaptic response to NMDA persisted, which was further reduced by the non-NMDA receptor antagonist 6-cyano-2,3-dihydro-7-nitroquinoxalinedione (CNQX). The non-NMDA glutamate receptor agonists kainate (KA), quisqualate (QA) and s-alpha-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (s-AMPA), evoked large inward currents due to the direct activation of receptors in Purkinje cells. NMDA applied to excised membrane patches failed to evoke any single-channel currents, whereas s-AMPA and QA caused small inward currents accompanied by marked increases in current noise. Spectral analysis of the s-AMPA noise in patches gave an estimated mean channel conductance of approximately 4 pS.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacologic evidence for NMDA, APB and kainate/quisqualate retinotectal transmission in the isolated whole tectum of goldfish

The optic tectum of goldfish with intact optic and toral marginal fiber tracts was isolated in a perfusion chamber where the effectiveness of antagonists was tested on synaptic field potential responses to stimulation of each afferent system. There were 3 main conclusions about excitatory synapses. First, monosynaptic activation of retinotectal synapses was not detectably antagonized by d-tubocurarine, implying there is no nicotinic cholinergic component to optic transmission nor strong cholinergic gating of optic terminals. Second, a significant component of retinotectical transmission was shown to be mediated by kainate and quisqualate receptors since 6,7-dinitroquinoxaline-2,3-dione and kynurenate strongly suppressed the optic field potential. In addition, activation of these synapses involves two previously undescribed N-methyl- d-aspartate (NMDA) and APB receptor subtypes since optic field potentials were partially suppressed by 2-amino-5-phosphonovalerate (APV), 2-amino-4-phosphonobutyrate (APB) and MK-801. This is the first evidence that APB receptors exist in the visual system central to the retina. Together, these results are consistent with the possibility that retinal ganglion cells use multiple glutamate receptor subtypes. Third, the optic tectum contains a population of intrinsic glutaminergic synapses activated by a non-optic input, the marginal fibers, which can be suppressed by both APV and kynurenate. The existence of tectal NMDA receptors whicha are not at primary optic synapses implies that APV used to interfere with rearrangement of optic fibers during development may act not only at afferent synapses but also at a more central component of the circuit.

Functional connections in the human temporal lobe

Connections in the human mesial temporal lobe were investigated using brief, single pulses of electrical stimulation to evoke field potential responses in limbic structures of 74 epileptic patients. Eight specific areas within these structures were stereotactically targeted for study, including amygdala, entorhinal cortex, presubiculum, the anterior, middle and posterior levels of hippocampus and the middle and posterior levels of parahippocampal gyrus. These sites were studied systematically in order to quantitatively assess the response characteristics and reliability of responses evoked during stimulation of pathways connecting the areas. Specific measures included response probability, amplitude, latency and conduction velocities. The results are assumed to be representative of typical human limbic pathways since all recordings were made interictally and response probabilities across sites were not found to differ significantly between non-epileptogenic vs. identified epileptogenic regions. Field potentials ranging in amplitude from less than 0.1 to greater than 6.0 mV were evoked ipsilaterally, with mean onset latencies and conduction velocities ranging from 4.4 ms and 3.64 m/s in the perforant pathway connecting entorhinal cortex to anterior hippocampus to 24.8 ms and 0.88 m/s in the pathway connecting the amygdala and middle hippocampus. Stimulation of presubiculum and entorhinal cortex were most effective in evoking widespread responses in adjacent limbic recording sites, whereas posterior parahippocampal gyrus appeared functionally separated from other limbic sites since its probability of influencing ipsilateral sites was significantly lower than any other area. It was particularly noteworthy that stimulation did not evoke responses in any sites in contralateral hippocampal formation; even though a large number of sites were tested with bilateral implantation of homotopic electrodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Depolarization-dependent actions of dihydropyridines on synaptic transmission in the in vitro rat hippocampus

Field potential and intracellular recordings were obtained in the in vitro hippocampal slice to study the effects on synaptic transmission of dihydropyridine (DHP) derivatives. Nimodipine or nifedipine by itself had little effect upon the postsynaptic response as determined by field potential analysis. However, facilitation became evident when DHP application was coupled with manipulations which induced a moderate degree of membrane depolarization. In accordance with the hydrophobic nature of these compounds, extensive washing in normal Krebs' solution failed to reverse the facilitation indicating that the DHP effects outlasted the induced depolarization. Nifedipine is photolabile and its actions were reversed when intense light was applied to the slice. Application of the DHP Bay K 8644, resulted in a similar depolarization-dependent increase in neuronal excitability which, upon washout and exposure to light, was at first attenuated and then reversed, resulting in a long-lasting depression of the EPSP that was sensitive to caffeine. This depressant action of Bay K 8644 appeared to be mediated at a site presynaptic to the pyramidal cell because the postsynaptic component of the field potential response to pulsed applications of glutamate was not altered. Intracellular recording from CA1 neurons supports a presynaptic locus for the depressant actions of Bay K 8644; spike threshold for synaptically evoked responses was greatly increased while spike threshold to direct depolarization of the soma was unchanged. These results indicate that DHPs can exert effects on synaptic transmission in hippocampal brain slice under conditions of moderate membrane depolarization.

Stimulus-Dependent Neuronal Oscillations in Cat Visual Cortex: Inter-Columnar Interaction as Determined by Cross-Correlation Analysis.

We have demonstrated previously that neurons in cat striate cortex, in response to their preferred stimuli, exhibit oscillatory responses in a frequency range of 40 - 60 Hz. Recently, we obtained evidence that such oscillatory responses can synchronize across columns. We have now performed an extensive analysis of this phenomenon for both unit and field potential responses. In addition, we studied the stimulus conditions leading to intercolumnar synchronization. We recorded both multi-unit activity and local field potentials from area 17 of adult cats with arrays of several electrodes. Interelectrode distances ranged from 0.4 to 12 mm. For all pairs of unit (n=200) and field potential (n=174) recordings, we computed auto- and cross-correlation functions. The modulation of the correlograms was quantified by fitting a damped sine wave (Gabor) function to the data. Cross-correlation analysis of the unit data revealed that in 90 out of 200 cases the recorded cells established a constant phase-relationship of their oscillatory responses. This occurred, on average, with no phase difference. If the receptive fields were nonoverlapping, we observed a synchronization primarily between cells with similar orientation preferences. Cells with overlapping receptive fields also showed a high incidence of synchronization if their orientation preferences were different. In this latter group, synchronization occurred even in cases where the stimulus was optimal for only one of the recording sites. Under conditions of monocular instead of binocular stimulation the oscillatory modulation of the responses was attenuated, but the cross-correlogram still indicated a significant interaction. Similar effects were seen with the application of stationary instead of moving stimuli. A synchronization of oscillatory field potential responses was observed in 136 out of 174 paired recordings. At all distances investigated, the probability of synchronization of field potential responses was independent of the orientation preferences of the cells. However, the strength of interaction decreased with increasing spatial separation. Control experiments showed that the synchronization of field potential responses was not due to volume conduction. The results demonstrate that oscillatory responses at separate cortical sites can transiently synchronize. The probability and strength of synchronization are dependent on the spatial separation of the recorded cells and their orientation preferences. In addition, the cross-columnar synchronization is influenced by features of the visual stimulus. It is suggested that this synchronization provides a mechanism for the formation of neuronal assemblies in the visual cortex.

Control of NMDA receptor-mediated activity by GABAergic mechanisms in mature and developing rat neocortex

The effects of diazepam and low concentrations of bicuculline methiodide (BMI) on the expression of long-latency N- methyl- d-aspartate (NMDA) receptor-mediated activity was studied in supragranular layers of juvenile (14–18 days old) and adult rat (⩾28 days) primary somatosensory cortex. In juvenile slices, orthodromic stimulation of layer VI/white matter evoked a long-lasting oscillatory field potential response which could be blocked by the NMDA receptor antagonist d(−)-2-amino-5-phosphonovaleric acid ( d-APV) and by diazepam. Similar d-APV-sensitive responses could be observed in adult slices when the GABAergic system was slightly suppressed by adding low doses of BMI to the bathing solution. Our findings indicate that a small decrease in the efficacy of the inhibitory system, whether caused by developmental events or by processes that modulate inhibitory electrogenesis, can lead to NMDA receptor-mediated synchronized afterdischarges, which might play an important role in the functional maturation of the neocortex and in susceptibility to epileptogenesis.

Anatomic organization and physiology of the limbic cortex

Ce rapport analyse l'organisation anatomique du systeme limbique, ses principales connexions avec les autres compartiments du cerveau et sa physiologie en rapport avec le comportement de l'animal

Generalized self-consistent reaction field theory in a multicenter-multipole ab-initio LCGO framework. I. Electronic properties of the water molecule in a Monte Carlo sample of liquid water molecules studied with standard basis sets

A generalized reaction field theory of surrounding medium effects on the electronic wavefunction of a solute is implemented at an ab initio level of theory. The reaction field (RF) potential, which in the exact theory is given as a compact functional form factorized into a solute charge density and a RF susceptibility, is calculated at a multicenter multipolar level of approximation. The static reaction field potential response function depends on the geometry and on the polarizability response tensor of the surrounding medium. The scheme is well adapted to study electronic systems in structurally fluctuating environments when these latter are simulated either with molecular dynamics or by Monte Carlo techniques. For nonhomogenous media, such as the environments around a water molecule immersed in a sample of equilibrated water molecules, a permanent electrostatic potential is also present. Solvent effects on one water molecule produced by a MC sample of water molecules interacting via MCY water-water potential and previously equilibrated have been studied at the RHF SCF level with STO-3G, 4-31G, 4-31G** and 6-31G** basis sets. Fluctuations of Mulliken populations, dipole moments, permanent solvent potentials and reaction potential components are studied for these 4 basis sets.

IN VITRO ACTIONS OF KETAMINE AND METHOHEXITONE IN THE RAT HIPPOCAMPUS

The effects of ketamine and methohexitone have been tested in vitro on rat CA1 pyramidal neurones using conventional extracellular and intracellular recording techniques. Ketamine 20-200 mumol litre-1 predominantly increased excitability by a postsynaptic action: it enhanced the amplitude of the antidromic (field) potential response in extracellular recordings; in intracellular studies depolarized or did not change the resting membrane potential; increased intrinsic excitability (assessed by direct stimulation); and reduced accommodation properties of CA1 neurones. Methohexitone 10-100 mumol litre-1 did not affect the amplitude of the antidromic field potential responses, tended to hyperpolarize and reduce the intrinsic excitability, but did not alter accommodation properties. At these concentrations these agents either did not affect or, in the case of ketamine, enhanced excitatory synaptic transmission on to the CA1 pyramidal neurones. Methohexitone 50 and 100 mumol litre-1 also induced a large, slow (several seconds) after depolarization which followed the conventional orthodromic response and may lead to action potential discharge. It is clear that these agents have multiple actions on CA1 pyramidal neurones in vitro and that ketamine and methohexitone in vitro influence excitability by different mechanisms.

PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY CARDIFF MEETING JULY 7-8, 1989: PREOXYGENATION IN THE ELDERLY PATIENT USING THE FOUR MAXIMAL BREATHS TECHNIQUE

The effects of the three inhalation anaesthetics enflurane, isoflurane and halothane were tested in vitro on accommodation of rat CA1 neurones. At near clinical concentrations (approximately 2.5%) the anaesthetics slightly depressed antidromic field potential responses. At the same concentrations the anaesthetics also blocked accommodation reversibly and reduced the after hyperpolarization of CA1 neurones. No significant changes in the threshold potential were observed, although the resting membrane potential was often increased in the presence of the anaesthetics. The action of enflurane was not blocked by propranolol 20 mumol litre-1 and enflurane had no obvious effect on the duration of Ca2+ spikes of CA1 neurones. It is concluded that the anaesthetics may have a direct effect on membrane K+ channels such as the Ca2+-activated K+ conductance and that the block of accommodation is unlikely to account for the proconvulsant action of enflurane.

Conditional stimulus probability and activity of hippocampal, cingulate cortical, and limbic thalamic neurons during avoidance conditioning in rabbits.

Past studies of the neuronal correlates of avoidance conditioning in rabbits have led to a model of information flow among structures of the limbic system. A hypothesis of the model is that unexpected stimuli activate certain hippocampal and cingulate cortical neurons. This activity in turn suppresses or "limits" the firing of limbic thalamic neurons. This hypothesis is tested in relation to stimuli classified as unexpected or expected on the basis of their incidence or "probability." Multi-unit and field potential responses in the anterior and posterior cingulate cortices (AC and PC), the dentate gyrus (DG), and the anterior ventral (AV) and medial dorsal (MD) thalamic nuclei were recorded during the acquisition and performance of a locomotor conditioned response (CR). The CR, stepping in an activity wheel in response to a 0.5-s tone (CS+), prevented the occurrence of a shock US scheduled 5 s after CS+ onset. The rabbits also learned to ignore a different tone (CS-), not predictive of the US. Training was given daily (120 trials, 60 with each CS in an irregular sequence) until behavioral discrimination reached criterion. After criterion, asymmetric probability (AP) sessions were given, in which the CS+/CS- proportions were .2/.8 or .8/.2. The AP sessions were the same as conditioning sessions except for the probability manipulation. A significant discriminative response, i.e., a greater neuronal discharge to the CS+ than to the CS-, developed in all regions during behavioral acquisition. The unit response in the AP sessions was enhanced in all areas by rare presentation of the CS-, compared with the equal and frequent CS- conditions. Rare presentation of the CS+ enhanced the unit response in the cortical areas (AC, PC, and DG), but it suppressed the firing of limbic thalamic (AV and MD) neurons. These results were supportive of the model. Rare CS+ presentations did not alter AV and PC neuronal activity in rabbits with subicular lesions, a result suggesting that an intact hippocampus is essential for normal neuronal responses to stimulus probability in the cingulate cortex and limbic thalamus.

Presynaptic actions of carbachol and adenosine on corticostriatal synaptic transmission studied in vitro

The purpose of this study was to identify, in the in vitro rat neostriatal slice preparation, an electrophysiological response corresponding to the activation of striatal neurons by cortical afferents, and to study the actions of a variety of putative neurotransmitters on modulating synaptic transmission at this synapse. Local stimulation of the neostriatal slice evokes a field potential composed of 2 prominent negativities. Experiments using calcium antagonists and tetrodotoxin indicate that the first negativity (N1) reflects the direct activation of intrinsic neurons and axons, while the second negativity (N2) is synaptically mediated. The afferent fibers eliciting the second negativity have not previously been identified because of the mixing of afferents within the striatum. However, similar field potential responses are elicited by stimulation of the corpus callosum, in which the only striatal afferents are crossed corticostriatal fibers. Kynurenate, gamma-D-glutamylglycine, and piperidine dicarboxylate all reversibly reduced or abolished N2, suggesting that the transmitter generating the response is an excitatory amino acid. Together, these results strongly suggest that N2 reflects activation of striatal neurons by corticostriatal afferents. Three putative striatal neurotransmitters, dopamine, acetylcholine and adenosine, were studied with respect to their ability to modulate the corticostriatal response. Dopamine had minimal effects on the waveform of the field potential. In contrast, carbachol or adenosine consistently reversibly reduced or eliminated N2. Atropine blocked carbachol's actions, while theophylline blocked adenosine's actions, indicating that the compounds were acting on muscarinic and adenosine receptors, respectively. To test whether these were primarily pre- or postsynaptic actions, we recorded the response to ionophoretically applied glutamate while simultaneously recording the synaptically evoked field potential from the same location.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute lead exposure transiently inhibits hippocampal neuronal activities in vitro

The effects of acute lead exposure on extracellularly recorded evoked responses in the CA1 region of hippocampal slices were investigated. Field potentials in response to paired-pulse stimulation were assessed while perfusing the slices with normal media and media containing lead in concentrations of 0.2 μM to 53 μM. The evoked population excitatory postsynaptic potentials decreased during lead exposure to a lesser extent that the orthodromically evoked population spike, whereas the presynaptic fiber volley remained unchanged. The maximal inhibition of the orthodromically evoked responses depended strongly on the lead concentration. The input-output relations of the orthodromic responses obtained during perfusion with lead significantly differed from those during control conditions. The somatic short-term potentiation obtained by paired-pulse stimulation increased during the lead exposure. Lead seemed to inhibit the evoked activities only transiently: within 20 min after lead onset, the recorded responses had reached the control level again in spite of further lead perfusion. In contrast to the orthodromically evoked responses, the antidromically evoked population spikes remained constant at all concentrations used. It is concluded from these results that lead acts presynaptically in the hippocampal slice preparation. Additionally, lead interferes with non-synaptic processes at the pyramidal neurons in the CA1. Possible influences of lead over different neurotransmitter systems are discussed.

Effects of raised extracellular potassium on the excitability of, and hormone release from, the isolated rat neurohypophysis.

1. Single neurohypophyses from male rats were maintained in an in vitro perifusion chamber. Ion-sensitive microelectrodes were introduced into the tissue to measure changes in [K+]o and [Ca2+]o during electrical stimulation. 2. Electrical stimulation at 6 Hz for 1 min and 30 Hz for 12 s raised [K+]o by 5.4 +/- 0.4 and 13.5 +/- 0.5 mM (mean +/- S.E.M., n = 8) respectively. To investigate the effects of raised [K+]o on the excitability of the neurosecretory terminals, stimulations were repeated in media of altered K+ concentration. The increase in [K+]o evoked by 6 Hz stimulation was elevated in 10 mM-K+ medium (133% of that in 5 mM-K+ medium) and reduced in 0 mM-K+ medium and in 25 mM-K+ medium. Thus it appeared that stimulus-induced changes in [K+]o might enhance the excitability of the tissue during electrical activation. 3. To test this hypothesis, we measured the field potential responses evoked by 0.5 Hz stimulation in media of different K+ concentrations. The size of the field potential was enhanced in 10 mM-K+ medium and depressed in 0 mM-K+ medium and in 25 mM-K+ medium. 4. Electrical stimulation (6 Hz, 1 min) decreased [Ca2+]o by 10.9 +/- 1.8% (n = 6). This decrease was absent in the presence of 1 microM-tetrodotoxin or 1 mM-cadmium. Again, the [Ca2+] response to stimulation was enhanced in 10 mM-K+ medium and depressed in 0 mM-K+ medium or 25 mM-K+ medium. 5. The release of vasopressin and oxytocin evoked by stimulation at 6 or 30 Hz from isolated neurohypophyses was measured by radioimmunoassay in a separate series of experiments. Stimulation at 30 Hz for 1 min released 5- to 6-fold more hormone than stimulation at 6 Hz for 5 min. Release evoked by 6 Hz stimulation was enhanced in 15 mM-K+ medium and depressed in 25 mM-K+ medium. 6. We conclude that the rise in [K+]o that accompanies high-frequency activation of axons and terminals in the neurohypophysis contributes to the facilitation of hormone release with increasing frequencies of stimulation, and in particular to the efficiency of the milk-ejection burst discharge of oxytocin neurones for evoking oxytocin release.

Field potential response changes in the rabbit olfactory bulb accompany behavioral habituation during the repeated presentation of unreinforced odors

Experiments were performed on waking rabbits to investigate the changes in both sniffing behavior and local field potential responses in the olfactory bulb during repeated exposure to unreinforced odors. Six rabbits were each implanted with 2 pairs of electrodes for differential recording of the bulbar extracellular field potential. Each animal was given 3 sequential sessions to each of 2 separate odors on 6 consecutive days, while monitoring the bulbar field potential activity and sniffing behavior. Behavioral sniffing responses exhibited rapid within-session decrement in amplitude and long term decrement across sessions. The within-session decrement showed spontaneous recovery between sessions. Both decremental changes in sniffing behavior were accompanied by changes in the bulbar field potential responses. The responses to novel odors were characterized by a reduction in amplitude of high frequency activity (40-80 Hz) and a corresponding increase in amplitude of low frequency activity (15-25 Hz). The high frequency component of the responses showed an initial increase in frequency to a novel odor on the first 3 presentations followed by a rapid decrease in frequency on subsequent trials in the first session which stabilized thereafter. No change in frequency or relative amplitude was observed for the low frequency component. The absolute difference between the odor evoked activity and the preceding control activity measured on each trial showed a significant decrement across sessions with no evidence for spontaneous recovery. The results demonstrate that olfactory bulb responses to novel unreinforced odors show both rapid and long-term changes which parallel changes in sniffing behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

ENFLURANE-INDUCED BURST FIRING OF HIPPOCAMPAL CA 1 NEURONES: In Vitro Studies using a Brain Slice Preparation

Enflurane can produce seizure activity in the cortical EEG, in vivo, at concentrations associated with surgical anaesthesia. The present study was designed to determine whether this seizure-like burst activity could occur in isolated cortical neurones. Enflurane altered synaptic transmission in the in vitro rat hippocampal slice preparation and produced seizure-like burst discharges of CA 1 neurones, at vapour concentrations equivalent to those obtained during anaesthesia (2-6 vol%; 0.5-1.5 mmol litre-1). Burst discharges occurred both spontaneously and in response to stimulation of stratum radiatum fibres in the CA 1 pyramidal region, but not in the dentate area. Low concentrations of enflurane (approx. 0.75 mmol litre-1), decreased the field potential responses of CA 1 neurones; however, dentate granule neurone responses were increased. Input/output analyses of field excitatory post-synaptic potential (EPSP) and population spike amplitudes revealed that the enflurane-induced depression of field potential responses was associated with decreases in synaptic input, whereas burst activity resulted from a decrease in the threshold of CA 1 neurones.

The action of valproate on spontaneous epileptiform activity in the absence of synaptic transmission and on evoked changes in [Ca 2+] 0 and [K +] 0 in the hippocampal slice

The effects of valproate (VPA) on neuronal excitability and on changes in extracellular potassium ([K +] 0) and calcium ([Ca 2+] 0) were investigated with ion selective-reference electrode pairs in area CA 1 of rat hippocampal slices. Field potential responses to single ortho- and antidromic stimuli were unaltered by VPA (1–5 mM). The afferent volley evoked in the Schaffer-commissural fibers was also unaffected. In contrast, VPA (1 mM) depressed frequency potentiation and paired pulse facilitation markedly. Decreases in [Ca 2+] 0 induced either by repetitive stimulation or by application of the excitatory amino acids N-methyl- d-aspartate and quisqualate were reduced, and the latter results suggest that VPA interferes with postsynaptic Ca 2+ entry. When synaptic transmission was blocked by lowering [Ca 2+] 0 (0.2 mM) and elevating [Mg 2+] 0 (7 mM), prolonged afterdischarges elicited by antidromic stimulation were blocked by VPA. VPA also suppressed the spontaneous epileptiform activity seen when [Ca 2+] 0 was lowered to 0.2 mM, without elevating [Mg 2+] 0. The amplitudes of the rises in [K +] 0 induced by repetitive orthodromic stimulation were only slightly depressed and those elicited by antidromic stimulation were generally unaltered by VPA, as were laminar profiles of stimulus-evoked [K +] 0 signals. These results indicate that VPA has membrane actions in addition to known effects on excitatory and inhibitory transmitter pools.

Modulation by prostaglandin D 2 of mitral cell responses to odor stimulation in rabbit olfactory bulb

Recent work in our laboratory has demonstrated that prostaglandin (PG) D2 and the enzyme activities for its biosynthesis and inactivation are highly concentrated in the olfactory bulb and that the mitral cell layer of the bulb is enriched with PGD2-binding protein. We therefore investigated the role of PGD2 in the processing of odor signals in the rabbit olfactory bulb by an electrophysiological technique. Iontophoretic (-100 nA, 20 s), intra-arterial (0.0125-0.1 mg/kg) and intravenous (i.v., 0.05-0.3 mg/kg) administration of PGD2 enhanced and prolonged the responses of mitral cells to some of the olfactory stimuli tested. The extent and duration of granule cell inhibition of mitral cells were assessed by recording field potential responses in the bulb to paired lateral olfactory tract volleys. The i.v. administration of indomethacin or diclophenac, both of which are inhibitors of PG biosynthesis, resulted in prolongation of the granule cell inhibition of mitral cells without any significant change of the conditioning amplitudes. It also caused the reduction of the spike responses of mitral cells to olfactory stimuli. After treatment with indomethacin, the i.v. administration of PGD2 (1 mg/kg) rapidly reduced the duration of the granule cell inhibition of mitral cells. These results indicate that PGD2 plays a modulatory role in the mitral cell responses to odor stimuli by suppressing the inhibitory synaptic inputs from granule cells to mitral cells.