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M Avoli

Publications and source records attributed to M Avoli.

At least 127 records · Page 7Linked to original sources
PubMed1988

Synaptic and non-synaptic mechanisms underlying low calcium bursts in the in vitro hippocampal slice.

1. The epileptiform activity generated by lowering extracellular [Ca++] was studied in the CA1 subfield of rat hippocampal slices maintained "in vitro" at 32 degrees C. Extracellular and intracellular recordings were performed with NaCl and KCl filled microelectrodes. 2. Synaptic potentials evoked by stimulation of the stratum radiatum and alveus were blocked upon perfusion with artificial cerebrospinal fluid (ACSF) containing 0.2 mM Ca++, 4 mM Mg++. Blockade of synaptic potentials was accompanied by the appearance of synchronous field bursts which either occurred spontaneously or could be induced by stimulation of the alveus. 3. Both spontaneous and stimulus-induced low Ca++ bursts recorded extracellularly in stratum pyramidale consisted of a negative potential shift with superimposed population spikes. This extracellular event was closely associated with intracellularly recorded action potentials rising from a prolonged depolarization shift. Steady hyperpolarization of the cell membrane potential decreased the amplitude of the depolarizing shift suggesting that synaptic conductance were not involved in the genesis of the low Ca++ burst. 4. Spontaneous depolarizing inhibitory potentials recorded in normal ACSF with KCl filled microelectrodes were reduced in size in low Ca++ ACSF. However, small amplitude potentials could still be observed at a time when low CA++ bursts were generated by hippocampal CA1 pyramidal neurons. 5. Bicuculline methiodide, an antagonist of gamma-aminobutyric acid (GABA), was capable of modifying the frequency of occurrence and the shape of synchronous field bursts. The effects evoked by bicuculline methiodide were, however, not observed when 81-100% of NaCl was replaced with Na-Methylsulphate.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1988

A depolarizing inhibitory postsynaptic potential activated by synaptically released gamma-aminobutyric acid under physiological conditions in rat hippocampal pyramidal cells.

We report that CA1 pyramidal neurons of the rat hippocampus respond to high intensity afferent stimulation by generating a late depolarizing potential that typically occurs between the early (fast) inhibitory postsynaptic potential (IPSP) and the late (slow) IPSP. This potential is reminiscent of the response seen after the application of 4-aminopyridine and can be blocked by bicuculline, indicating that GABAA receptors are involved in its generation.

4-Aminopyridine↗
PubMed1987

Seizure-like discharges induced by lowering [Mg2+]o in the human epileptogenic neocortex maintained in vitro.

Seizure-like discharges were observed in slices of human epileptogenic neocortex maintained in vitro when [Mg2+]o was lowered near to zero. This type of epileptiform activity: (1) could occur spontaneously or following extracellular focal stimuli; (2) resembled the electrographic pattern associated with tonic-clonic seizures; (3) was accompanied by increases in [K+]o (maximally 6.2 mM from a baseline of 3.25 mM) and decreases in [Ca2+]o (maximally 0.23 mM from a baseline of 1.8 mM). Application of the selective antagonist of N-methyl-D-aspartate (NMDA) receptors, DL-2-amino-5-phosphonovalerate, suppressed in a reversible manner both spontaneous and stimulus-induced seizure-like discharges, suggesting that NMDA-activated conductances are important for the genesis of prolonged epileptiform discharges generated by human epileptogenic neocortical slices.

Epilepsies, Partial↗
PubMed1987

Bursting in human epileptogenic neocortex is depressed by an N-methyl-D-aspartate antagonist.

Intracellular recordings were performed in human neocortical neurons in 'in vitro' slices of brain samples excised during surgical treatment of epilepsy. In 14 of 38 neurons obtained from cortex exhibiting interictal spiking, bursts of action potentials arising from a synaptic depolarizing potential could be elicited by extracellular focal stimulation of adequate strength. The N-methyl-D-aspartate (NMDA) antagonist 2-amino-5-phosphonovalerate (APV) was capable of reducing and eventually blocking these bursts without affecting the repetitive firing evoked by depolarizing intracellular pulses or the membrane input resistance. These data suggest a role played by NMDA receptors in the bursting activity displayed by human neurons from spiking cortical areas and demonstrate a potential use of NMDA antagonists as antiepileptic drugs.

2-Amino-5-phosphonovalerate↗
PubMed1987

Intracellular recordings in pericruciate neurons during spike and wave discharges of feline generalized penicillin epilepsy.

Concurrent EEG and intracellular recordings from pericruciate neurons of cats obtained before and after i.m. injection of penicillin inducing the syndrome of feline generalized penicillin epilepsy (FGPE) characterized by spike and wave (SW) discharge in the EEG, display large excitatory postsynaptic potentials (EPSPs) at the time of the EEG 'spike' which alternate with hyperpolarizing potentials occurring in coincidence with the EEG 'wave' component of the SW complex. The large EPSPs trigger discharges of single or multiple high-frequency action potentials which do not show a progressive decrement in amplitude nor an appreciable increase in duration. These bursts thus differ in some respects from typical paroxysmal depolarization shifts. The hyperpolarizing potentials show an early phase which is reversed by intracellular Cl- injection or diffusion and thus behaves like a classical inhibitory postsynaptic potential (IPSP). The late phase is unaffected by Cl-. Hyperpolarizing potentials of pericruciate neurons induced by antidromic activation of the cerebral peduncle (CP) or by direct cortical stimulation are not altered after i.m. injections of penicillin at doses sufficient to induce generalized SW discharge. The early phase of hyperpolarization both before and after i.m. penicillin is reversed by intracellular Cl- injection or diffusion, the late phase remains unchanged. The early phase thus represents a classical IPSP, which does not appear to be affected by the low brain penicillin concentrations sufficient to induce generalized SW discharge. It is concluded that this form of epileptic discharge cannot be attributed to blockage of phasic (presumably somatic) postsynaptic inhibition by penicillin. These results indicate that to regard all forms of epileptic discharge as the consequence of a blockage of gamma-aminobutyric acid-mediated phasic postsynaptic inhibition acting on the soma represents an unduly restrictive view of epileptogenesis.

Animals↗
PubMed1987

A GABAergic depolarizing potential in the hippocampus disclosed by the convulsant 4-aminopyridine.

Intracellular recordings from hippocampal pyramidal cells in the CA1 subfield of the 'in vitro' slice in the presence of 4-aminopyridine (4-AP, 5-50 microM) revealed a long-lasting (up to 1.5 s) depolarizing potential which occurred either spontaneously or following orthodromic stimulation. This potential was: capable of blocking both direct and synaptic activation of the cell; sensitive to bath application of low concentrations of bicuculline methiodide; and associated to an extracellular current sink in the dendrites as suggested by the extracellular field potentials recorded at different levels along an axis perpendicular to the stratum pyramidale. It is concluded that the long-lasting depolarizing potential evoked by 4-AP is caused by the activation of GABA receptors localized in the dendritic region of the CA1 subfield.

4-Aminopyridine↗
PubMed1987

Control of spontaneous epileptiform discharges by extracellular potassium: an "in vitro" study in the CA1 subfield of the hippocampal slice.

1. The effects evoked by changing [K+]o upon the synchronous epileptiform discharges (SEDs) generated in the presence of GABA antagonists were studied in the "in vitro" hippocampal slice with extra- and intracellular recordings. [K+] in the artificial cerebrospinal fluid (ACSF) was varied in steps of 1 or 2 mM between 3.25 and 10.25 mM. 2. Spontaneous SEDs occurred rarely at [K+]o lower than 5.25 mM. Augmenting [K+]o from 5.25 to 10.25 mM caused a four to five fold increase in the frequency of occurrence of SEDs while the duration of each SED was inversely related to the rate of occurrence. 3. Similar findings were observed when the CA1 subfield had been surgically disconnected from the CA2-CA3 subfields. In these experiments SEDs occurred independently in the two regions, but at any given [K+]o SEDs in the CA3 subfield displayed a frequency two to three times higher than that of SEDs generated in the CA1 area. 4. The intracellular correlate of the SEDs in the CA1 subfield either intact or isolated from the CA2-CA3 ones was a large amplitude depolarization (duration 100-600 ms) associated with a burst of action potentials. This intracellular event, which was similar to the paroxysmal depolarizing shift (PDS) recorded in focal models of epilepsy "in vivo", behaved largely like a synaptic phenomenon when the resting membrane potential (Vm) was changed with intracellularly injected current. A long lasting (half-width: 0.3-2 s in 6.25 mM [K+]o) hyperpolarizing potential usually followed the PDS and could be inverted by hyperpolarizing the Vm by 15-25 mV. When [K+] in the ACSF was raised from 7.25 to 10.25 mM, pyramidal cells depolarized in a dose related fashion. At the same time the post-PDS hyperpolarization decreased in duration and peaked earlier, thus curtailing the depolarizing envelope of the PDS. Consequently, the effect of increasing [K+]o was that of evoking more frequent, but shorter PDSs. 6. These findings demonstrate that the appearance of spontaneous SEDs in the presence of GABA antagonists is dependent upon [K+]o. The effects of evoked by increasing [K+]o are presumably mediated through: (i) a decreased strength of K+ repolarizing conductances; (ii) an increased efficacy of synaptic potentials; (iii) a steady depolarization of the neuronal membrane. The modulation of the frequency of occurrence of SEDs appears to be related to a decreased duration of the hyperpolarization which follows the PDS, a potential which is largely mediated by a K+ conductance.

Animals↗
PubMed1986

Inhibitory potentials in neurons of the deep layers of the in vitro neocortical slice.

Neocortical neurons in slices of the rat sensorimotor region maintained in vitro generate postsynaptic potentials (PSPs) in response to focal extracellular stimulation. These PSPs are mainly depolarizing at the resting membrane potential (Vm) but a sequence of depolarizing-hyperpolarizing potentials is often disclosed by depolarizing the Vm. The stimulus-induced hyperpolarization can last up to 1000 ms and show two components: the early one (peak latency 10-20 ms), is inverted by diffusion of Cl- into the cell; the late one is diminished by augmenting [K+]o. The membrane conductance is increased throughout the stimulus-induced hyperpolarization, mainly during the first 10-60 ms. A decrease in excitability results from both the hyperpolarizing trend and the conductance increase. The latter is more effective in decreasing depolarizing than hyperpolarizing pulses of current injected intracellularly.

Animals↗
PubMed1986

Thalamocortical and intrathalamic interactions during slow repetitive stimulation of n. centralis lateralis.

Extracellular single unit activity was recorded simultaneously in cortex (anterior part of the middle suprasylvian gyrus, MSSG) and thalamus (n. ventralis anterior, VA; n. lateralis posterior, LP) during repetitive low frequency stimulation (RLFS) of n. centralis lateralis (CL) in lightly anesthetized cats. Such stimulation induced typical recruiting responses in the cortical EEG consisting of long-latency, surface-negative waves reversing in polarity at 0.1-2mm depth. These cortical EEG responses were associated with long-latency (8-20 ms) action potential (AP) discharges of cortical neurons appearing with the 2nd stimulus of the train. The number of AP discharges and response latency increased as the train of CL stimuli progressed. In 12 of these neurons there was a short-latency (up to 2-5 ms) response which, however, did not show incremental features during RLFS. Thalamic neurons in VA usually responded to the first stimulus within a train of RLFS of CL, while LP neurons responded only to the 2nd or 3rd stimulus. Peristimulus time histograms (PSTHs) of AP discharges in VA showed an increase in both number and latency of APs as the train of stimuli progressed. This was also observed in those thalamic neurons in LP which changed their firing during RLFS of CL. The peak of firing of 20 VA neurons preceded, and that of 7 followed that of the MSSG neurons, while 6 VA and MSSG neuronal pairs reached their peak firing simultaneous; peak firing of 29 LP neurons preceded, and that of 21 followed the firing peak of MSSG neurons. The thresholds of the incremental responses of MSSG, VA and LP neurons to progressively increased intensity of RLFS of CL were different: MSSG and VA neurons changed their firing pattern at an intensity incapable of modifying the activity of LP neurons. When stimulation intensity was increased to a level sufficient to change the responses of both neurons of a given pair (either MSSG-VA or MSSG-LP) the time sequence of involvement in the incremental process was in the following order: VA, MSSG, LP. Within a range of RLFS extending from 2-20 Hz, stimulation at 6.6 Hz (150 ms interstimulus intervals) induced the most prominent incremental responses both in the cortex and thalamus, i.e. response increases were largest when each subsequent stimulus occurred 50-130 ms before the expected rebound excitation following the preceding response.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Depression of hippocampal low calcium field bursts by the antiepileptic drug valproic acid.

The antiepileptic drug valproic acid (VPA) reduces the occurrence of the rhythmic and synchronous bursts produced by hippocampal neurons maintained 'in vitro' and bathed in Ringer-containing low-Ca2+ (0.2 mM), high-Mg2+ (4.0 mM). In this medium, synaptic transmission is blocked, thus demonstrating an action of VPA unrelated to potentiation of GABAergic phenomena. This conclusion is reenforced by the persistence of VPA effects in the presence of bicuculline. Also, the VPA doses effective in reducing the low-calcium synchronous burst in the hippocampal slice are similar to the free plasma levels of VPA observed to exert anticonvulsant effects in kindled rats.

Animals↗
PubMed1985

Intracortical inhibitory mechanisms are preserved in feline generalized penicillin epilepsy.

Intracortical inhibition elicited by direct cortical stimulation or by stimulation of the cerebral peduncle, the latter inducing recurrent inhibition of cortical neurons, is not significantly affected by intramuscular injection of penicillin sufficient for inducing the syndrome of feline generalized penicillin epilepsy characterized by generalized spike and wave (SW) discharges in the EEG. This raises to four the number of paradigms of presumably postsynaptic inhibition resistant to penicillin concentrations sufficient to produce generalized SW discharges, a form of epileptic discharge which thus cannot be attributed to blockage of the forms of intracortical postsynaptic inhibition so far tested.

Animals↗
PubMed1984

Penicillin induced hyperexcitability in the in vitro hippocampal slice can be unrelated to impairment of somatic inhibition.

The effects induced by penicillin (PEN) upon the synaptic responses of CA1 hippocampal pyramidal cells (HPCs) were studied in the 'in vitro' slice. Low concentrations of PEN (0.17-0.34 mM) evoked an increase in amplitude and duration of the orthodromic excitatory post-synaptic potential induced by stratum radiatum, while stimuli which were subthreshold in control conditions became effective in eliciting action potentials. These changes were not paralleled by any decrease of the recurrent inhibitory post-synaptic potential due to inhibitory interneurons located at or near the soma. However, the latter decreased and then disappeared as PEN concentrations were brought to levels higher than 0.68 mM. Since low concentrations of PEN increase CA1 HPCs responsiveness without decreasing somatic inhibition, it is concluded that this action is probably due to a reduced dendritic inhibitory mechanism.

Animals↗
PubMed1984

Differential participation of some 'specific' and 'non-specific' thalamic nuclei in generalized spike and wave discharges of feline generalized penicillin epilepsy.

Extracellular single unit and electroencephalographic (EEG) activity during generalized spike and wave discharges (SW) induced by i.m. penicillin was recorded simultaneously in the cortex, in a 'specific' thalamic nucleus (n. lateralis posterior, LP) and in some 'non-specific' thalamic nuclei (n. centralis medialis, NCM; n. centrum medianum, CM; n. centralis lateralis, CL) Computer-generated EEG averages and histograms of single unit activity were triggered by either peaks of EEG transients or action potentials. The time at which cortical neurons (66/66) were most likely to fire was during the 'spike' of the SW complex while absence of firing was the rule during the 'wave'. Most LP neurons (23/26) showed a similar pattern, 3 cells firing preferentially during the 'wave'. In NCM only 17 of 39 neurons fired during the 'spike', 8 of 39 neurons during the 'wave' while the others showed no change in their firing pattern during SWs. Twenty-six of 30 CM and 20 of 24 CL neurons fired during the 'spike' of SW; the other cells in these nuclei did not change their firing pattern during SWs. When present, rhythmic fluctuations in firing linked to SW discharge were less prominent in these 'non-specific' thalamic nuclei than in cortex and LP. Furthermore, participation of NCM, CM and CL neurons in the SW rhythm occurred only after neurons in cortex and LP had become involved in it. Thus, as is the case for cortical neurons, the main firing pattern of thalamic cells during SWs consists of an oscillation between 'excitation' during the 'spike' and 'inhibition' during the 'wave' of the SW complex. However, the coupling between cortical and thalamic neuronal firing is less intimate for cells of the 'non-specific' thalamic nuclei than for a 'specific' nucleus such as LP. Thus, at least some 'specific' thalamic nuclei are more intimately involved in the mechanism of SW discharge than the midline intralaminar nuclei.

Animals↗
PubMed1984

Simultaneous recording of cortical and thalamic EEG and single neuron activity in the cat association system during spindles.

Simultaneous recording of the EEG and single unit activity in cortex and thalamus shows that during spindles the cortical and thalamic EEGs within a given thalamocortical sector are highly correlated, but that the firing of only a fraction of cortical and thalamic neurons shows a close mutual correlation or exhibits a close relationship to the cortical and thalamic EEGs. Thus, only a fraction of thalamic and cortical neurons is involved in generating spindles. The synchronized activity of these neurons, even if some of it is subliminal for action potential discharge, suffices to produce a recordable EEG signal.

Animals↗
PubMed1984

Transition from spindles to generalized spike and wave discharges in the cat: simultaneous single-cell recordings in cortex and thalamus.

The relationships between the activity of the cortex and that of a "specific" (n. lateralis posterior, LP) and an intralaminar thalamic nucleus (n. centralis medialis, NCM) were studied in the cat during the transition from spontaneous spindles to generalized spike and wave (SW) discharge following i.m. penicillin injection. The EEG and extracellular single-unit activity were recorded in cortex and thalamus during the spindle stage and at different intervals after penicillin until well developed SW discharges were present. Computer-generated EEG averages and histograms of single-unit activity were triggered by either peaks of cortical or thalamic EEG transients or by cortical or thalamic action potentials. In agreement with previous observations, cortical neurons increasingly fired during the spindle wave as it was transformed into the "spike" of the SW complex, while a period of neuronal silence gradually developed as the "wave" of the SW complex emerged. Similar changes developed in the thalamus, particularly in LP, either concurrently with or more often after the onset of the changes in the cortex. Most neurons in NCM, continued to fire randomly even after well developed SWs and rhythmic neuronal discharges had developed in cortex and LP. Only 4/11 NCM neurons did ultimately exhibit a rhythmic firing pattern similar to that seen in the cortex and LP. The correlation between cortical and thalamic unit activity was low during spindles, but gradually increased during the development of SW discharges. These data confirm that the cortex is the leading element in the transition from spindles to SWs. Increasingly, in the course of this transition, cortical and thalamic neuronal firing becomes more intimately phase-locked. This mutual interrelationship appears to be more pronounced between cortex and "specific" than intralaminar thalamic nuclei.

Action Potentials↗
PubMed1983

Enhanced response of cortical neurons to thalamic stimuli precedes the appearance of spike and wave discharges in feline generalized penicillin epilepsy.

Peristimulus time histograms of extracellularly recorded action potential discharges of cortical neurons in response to single shock and/or repetitive stimulation of 'specific' and 'non-specific' nuclei of the thalamus were studied after i.m. penicillin injection during a period corresponding to that of the development of spike and wave (SW) discharges of feline generalized penicillin epilepsy (FGPE). After i.m. penicillin cortical neurons displayed an enhancement of both the excitatory and 'inhibitory' phases of their responses to single shock stimulation of n. centralis medialis (NCM). This increase was even more pronounced for responses induced by repetitive stimulation of NCM at the frequencies inducing typical recruiting responses. These changes always preceded the appearance of SW discharges. Changes of the responses of cortical neurons to single shock and repetitive stimulation of 'specific' thalamic nuclei after penicillin were weak and inconsistent, although when observed were characterized by an enhancement of both excitatory and 'inhibitory' phases. The latter appeared not to decrease after i.m. penicillin. These data suggest that the appearance of SW discharges of FGPE is closely related to an increased responsiveness of cortical neurons to thalamocortical volleys arising from the so-called 'non-specific' nuclei. This facilitation of the recruiting process is accompanied by an increase of both excitatory and 'inhibitory' phases of the cortical neuronal responses induced by the volleys.

Animals↗
PubMed1983

Participation of cortical and thalamic cells in the feline association system to thalamocortical recruiting responses.

Pairs of neurons located in mutually related sites in cortex (middle suprasylvian gyrus) and specific thalamus (n. lateralis posterior and pulvinar), were recorded simultaneously during recruitment responses. Cortical neurons showed an increased firing probability in association with the surface negative cortical recruiting waves, this phase being followed by a period of firing depression. One group of thalamic neurons, identified as thalamocortical, fired earlier than the simultaneously recorded cortical units. A second group was silenced during the period of cortical firing but tended to fire action potentials during the period of cortical firing depression. These data show that thalamic neurons in specific nuclei are involved in the process of thalamocortical recruitment.

Animals↗