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M Avoli

Publications and source records attributed to M Avoli.

At least 145 records · Page 8Linked to original sources

Participation of cortical recurrent inhibition in the genesis of spike and wave discharges in feline generalized penicillin epilepsy.

Cortical recurrent inhibition (RI) evoked in pericruciate cortex by antidromic stimulation of the cerebral peduncle (CP) was studied in normal cats and in cats exhibiting the signs of feline generalized penicillin epilepsy (FGPE) following the i.m. injection of penicillin. Two measures of RI evoked by antidromic CP stimulation were used: (i) the averaged focal potential in the pericruciate gyrus; and (ii) the duration of the suppression or diminution of extracellularly recorded action potential (ap) discharge of antidromically activated pericruciate neurons measured in peristimulus time histograms (PSTHs). After i.m. injection of 350,000 IU/kg of penicillin RI remained preserved as long as only generalized spike and wave (SW) discharges appeared in the EEG, although in 5/17 neurons a modest to moderate reduction in the duration of RI occurred once SW discharges had appeared in the EEG. This inconstant reduction was probably not caused by a direct anti-inhibitory action of penicillin, but is a consequence of the increased number of ap discharges curtailing RI. At the small concentrations of penicillin existing in brain in FGPE its anti-inhibitory action evident with larger concentrations cannot be demonstrated. When focal or generalized tonic-clonic (T-C) seizures occurred, RI was reduced in slightly more than half of the instances for a few minutes before the onset of these seizures. This suggests that the transition from SW discharge to T-C seizure may be caused by a breakdown of RI.

Animals↗

Interactions between amino acid neurotransmitters and flurazepam in the neocortex of unanesthetized rats.

The effects induced by the benzodiazepine flurazepam (FLU) upon neuronal responses to glutamic acid (GLUT), gamma-aminobutyric acid (GABA), and glycine (GLY) were studied in the cortex of unanesthetized rats using single-unit extracellular recordings in conjunction with iontophoretic techniques. The application of FLU (5-20 nA) did not affect excitatory responses to GLUT, but the spontaneous firing rate was depressed by equivalent doses of this benzodiazepine. A selective increase of GABA, but not of GLY-induced responses was seen when either low currents (5-10 nA) of FLU or GLUT driving currents were used to study the neuronal responses of the inhibitory amino acids upon steady neuronal firing. Our data demonstrate that in unanesthetized animals FLU does not affect GLUT-induced effects while it selectively increases GABA-mediated inhibition.

Amino Acids↗

An analysis of penicillin-induced generalized spike and wave discharges using simultaneous recordings of cortical and thalamic single neurons.

To study the relationship between cortical and thalamic single-neuron activity during spike and wave (SW) discharge of feline generalized penicillin epilepsy (FGPE), extracellular single-unit and local electroencephalogram (EEG) activity were recorded simultaneously from pairs of neurons, one located in the cortex of the middle suprasylvian gyrus (MSS), the other in the dorsal thalamic nuclei (n. lateralis posterior or pulvinar). These two areas are anatomically and functionally closely interrelated. Computer-generated EEG averages and histograms of single-unit activity triggered by either peaks of cortical or thalamic EEG transients or by cortical or thalamic action potentials (aps) showed that cortical neurons in the MSS fired at the time of the spike of the SW complex, while at the time of the wave they became silent. Two populations of thalamic neurons also fired maximally during the spike of SW discharge, but they differed in the precise timing of their firing in relation to that of the simultaneously recorded cortical neuron. The first group of thalamic neurons tended to fire 5-45 ms before the cortical neuron. Of these 28 neurons, 9 were antidromically and 2 orthodromically activated by cortical stimulation. The neurons of the second group tended to fire 0-45 ms after the cortical neuron. Cortical stimulation activated 15 of these 19 neurons orthodromically and 2 antidromically. A third and smaller population of thalamic neurons (n = 8) increased its firing probability during the wave of the SW complex and decreased it during the spike. In 74% of the pairs of neurons the cyclic alternation of excitation and "inhibition" associated with SW activity appeared in the cortex by 1-3 cycles earlier than in the thalamus. This was most common when the thalamic neuron of the pair reached its peak firing probability before the simultaneously recorded cortical neuron. In 11 pairs of neurons the same rhythmic alternation of excitation and "inhibition" of neuronal firing was seen in both the cortex and thalamus during SW discharges evoked by single-shock stimulation of nucleus centralis medialis. These data demonstrate that both cortical and thalamic neurons participate in the SW firing pattern of FGPE by undergoing periods of mutually phase-locked cyclic alternations of excitation and "inhibition" at the frequency of the EEG SW rhythm. Although the initial steps leading to generalized SW discharge in FGPE take place in the cortex, the thalamus soon becomes entrained in the SW rhythm.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Participation of corticothalamic cells in penicillin-induced generalized spike and wave discharges.

Single unit extracellular recordings were performed in the cortex of awake painlessly immobilized unanesthetized cats during generalized spike and wave discharges (SW) induced by i.m. penicillin. Corticothalamic cells were identified in cortical areas 3a and 4 gamma by stimulating n. ventralis lateralis (VL) and in cortical areas 5 and 7 by stimulating n. lateralis posterior (LP). Twelve of 24 neurons antidromically invaded from VL were also pyramidal tract cells. Two of 11 neurons antidromically invaded from LP also displayed orthodromic responses. Corticothalamic cells fired bursts of action potentials in association with the 'spike' whereas a period of inhibition was associated with the 'wave' of the SW complex. The data suggest that in this experimental model the appearance of SW in the thalamus is due to secondary activation of thalamic neurons by volleys arising from the cortex and mediated through corticothalamic connections.

Animals↗

Laminar analysis of spindles and of spikes of the spike and wave discharge of feline generalized penicillin epilepsy.

Intracortical laminar profiles of spindles and spikes of spike and wave complexes in feline generalized penicillin epilepsy were studied using two methods: (i) sequential microelectrode recordings at various cortical depths, and simultaneous recordings at multiple cortical depths using a fine multi-contact electrode. Raw EEG data and EEG epochs averaged with respect to peaks of surface EEG waves were analyzed. Spindles and the spikes of the spike and wave complexes showed similar laminar profiles. This supports the hypothesis that the two are basically the same cortical electrophysiological phenomenon, the spike being a spindle wave enhanced and slightly altered because of the penicillin-induced increased cortical excitability. The latter causes the weight of the thalamic input to shift from superficial to more deep lying synapses. Both surface negative and surface positive phases of spindles and of spikes of spike and wave complexes show similar laminar profiles, those of the former suggesting activation of excitatory synapses in the superficial cortical layers, those of the latter suggesting activation of more deeply located excitatory synapses. The profiles generally conform to the dipole hypothesis of cortical electrogenesis and suggest that spindles and spikes of spike and wave complexes are generated by the same pyramidal neurons, probably through activation of the same sets of synapses. Some inconstant and relatively minor deviations of the laminar profiles from the pattern predicted by the dipole theory of cortical electrogenesis were encountered and are tentatively explained in the light of some of the complexities of the microanatomical organization of mammalian neocortex.

Action Potentials↗

Neuronal responses to putative neurotransmitters during penicillin epileptogenesis.

An epileptogenic process was induced within the rat frontoparietal cortex by microiontophoretic applications of penicillin. The temporal development of the penicillin-induced activity was divided into (a) a first phase characterized by an increased rate of neuronal firing, (b) a pre-paroxysmal phase wherein neurons began to fire clusters of action potentials and (c) a paroxysmal phase characterized by a discharge of action potential clusters. The excitatory responses to glutamate and to acetylcholine appeared to be enhanced during the first and pre-paroxysmal phases, whereas a loss of the excitatory effectiveness of both glutamate and acetylcholine occurred during the final paroxysmal phase. Forty nine of 69 neurons studied (71%) showed a decreased sensitivity to gamma-aminobutyrate during the first phase of penicillin iontophoresis. However, during this same time, glycine-induced inhibition was not decreased. During the second phase, gamma-aminobutyrate-induced inhibition was even less effective, and glycine started to lose effectiveness. During the third phase, both these inhibitory neurotransmitters failed to affect the neuronal activity. The other 29% of the neurons studied showed a general diminution to the actions of both gamma-aminobutyrate and glycine when penicillin-induced action potential clusters appeared. Our results suggest that penicillin interferes with gamma-aminobutyrate-mediated inhibition in a large proportion of cortical neurons of the rat. Furthermore, these cortical neurons show changes in the responses to both excitatory and inhibitory neurotransmitters that closely parallel the development of penicillin-induced activity.

Action Potentials↗

Effects of post-ictal depression on experimental spike and wave discharges.

The effects of post-ictal depression on spike and wave (SW) discharges of feline generalized penicillin epilepsy (FGPE) were studied. After tonic-clonic seizures which are not uncommon in FGPE spindle bursts appeared during the post-ictal period. Upon recovery spontaneous and thalamically evoked SW discharges reappeared. Spindles before penicillin and during post-ictal depression showed a similar intraburst frequency (twice that of SW discharges) in the same animal. These findings add further evidence to the notion that any depression of cortical excitability in FGPE leads to replacement of SW by spindles and thus supports the hypothesis that SW discharges occur in hyperexcitable cortex in response to normally spindle-inducing thalamocortical volleys.

Animals↗

The effects of transient functional depression of the thalamus on spindles and on bilateral synchronous epileptic discharges of feline generalized penicillin epilepsy.

A transient functional depression of thalamic activity (TFDTA) was induced in acute experiments in cats by the microinjection of 25% KCl into the thalamus. Spontaneous and evoked thalamic electrical activity was markedly depressed at the site of KCl microinjection. Spread of this depression to other thalamic areas often occurred, mainly when KCl was injected into the midline thalamus. In normal cats both spontaneous and evoked cortical spindle bursts as well as other evoked thalamocortical responses were reduced or abolished during the KCl-induced TFDTA. The generalized spike-and-wave discharges of feline generalized epilepsy were also suppressed for the duration of TFDTA, while incidental focal cortical interictal and ictal epileptic discharges, as well as generalized tonic-clonic seizure discharge, remained unaffected. The same effects were observed in animals with lesions of the mesencephalic reticular formation, indicating that the suppression of spindles and spike-and-wave discharges cannot be attributed to a release of the activity of the reticular formation by the TFDTA. An unexplained occurrence of generalized tonic-clonic EEG seizure was observed in most cases late after thalamic KCl microinjection, usually after the spike-and-wave discharges had recovered. These data are consistent with the hypothesis that the spontaneous bilaterally synchronous epileptic bursts of feline generalized penicillin epilepsy are not only closely related to spindles but are crucially dependent on thalamic inputs to the cerebral cortex.

Animals↗