Changes of activity of cortical neurons induced by acetylcholine in adult and young rats.

Acetylcholine was applied microiontophoretically by means of multibarrel electrodes to neurons in the sensorimotor cortex of adult, 18-, 15-, 12-, and 9-day-old rats anesthetized with urethane. A total of 229 neurons was recorded; only 22 of them were in 18- and 15-day-old rats because of similarity of results with those from adult as well as 12-day-old animals. In adult rats 43 of 58 neurons recorded in infragranular layers responded to acetylcholine with a marked increase in their firing. In 12-day-old rats the incidence of excitatory responses to acetylcholine was also high: 59 of 86 cells again were localized predominantly in deep cortical layers (V and VI). A marked difference was observed in 9-day-old rats: only 15 of 63 neurons were excited by acetylcholine. A majority of cells did not respond at all--including units localized in infragranular layers. Two cells in layer V responded to acetylcholine by an inhibition. Our results indicate that there is a marked increase in cholinoceptivity of cortical neurons between postnatal days 9 and 12. This finding is in agreement with the finding that local application of acetylcholine can elicit an epileptogenic focus in 12-day but not in 9-day-old rat pups.

Changes in the activity of rat cortical and hippocampal neurones after the iontophoretic administration of beta-endorphin, glutamate and GABA.

The effect of microiontophoretically administered beta-endorphin on the activity of 62 cortical and hippocampal neurones was studied in acute experiments on 14 rats. The effectiveness of beta-endorphin was first of all verified in the isolated guinea pig ileum, the mouse was deferens and in a study if its analgetic and catatonic effect in rats. Beta-endorphin only mildly depressed the spontaneous activity of cortical neurones, but markedly inhibited the activity stimulated by the microiontophoretic administration of glutamate. In the hippocampus, beta-endorphin stimulated the activity of all the studied neurones when only low ejection currents were used and activation persisted for 1-4 min after terminating administration. With higher ejection currents, the discharge frequency rose enormously and not even GABA blocked this effect. The excitatory effect of beta-endorphin on the hippocampal neurones may possibly be the basis of the epileptogenic action of this substance.

Effect of diphenylhydantoin on unit activity in a cortical epileptogenic focus in the rat.

The correlation between discharges of a penicillin focus and unit activity was studied in the sensorimotor cortex of 30 adult male curarized rats under urethane anaesthesia. Among 43 units, three types of activity could be differentiated: (1) units without any relationship to focal discharges (7% of neurones); (2) units with a biphasic reaction, a burst of spikes during the main negative deflection of the focal discharge followed by a period of inhibition (72%); (3) units inhibited during the whole duration of the focal discharge (21%). The effects of diphenylhydantoin (60 mg/kg i.p.) were studied on 35 units--20 of them were also recorded before administration of diphenylhydantoin and thus included in the above group. Diphenylhydantoin led to decreased representation in groups (1) and (2), whereas the percentage of units inhibited during the focal discharge was increased from 21 to 31%. A decrease in number of spikes in the excitatory burst and/or the prolongation of the inhibitory phase was a consequence of diphenylhydantoin administration in 18 out of 20 neurones with long-lasting recording. A direct action of diphenylhydantoin on the primary epileptogenic focus was thus demonstrated.

Activating effect of nasal and oral hyperventilation on epileptic electrographic phenomena: reflex mechanisms of nasal origin.

In experiments on animals, airflow through the nasal cavity elicits rhythmic synchronized activity that can trigger and/or elicit epileptic electrographic activities in the limbic structures of the brain. This could be demonstrated in studies of lower vertebrates (frogs and turtles). In the turtle the elicited paroxysmal activity often had the shape of regular high-voltage activity in the theta-frequency range (average frequency, 4.1 Hz). It was further proven in clinical experiments that nasal deep breathing with a closed mouth effectively activates epileptic electrographic phenomena of a temporal (limbic) origin. The activating effect was more pronounced on the side ipsilateral to the ventilated nasal meatus. It could also be evoked by air insufflation into the nasal cavity. This effect was suppressed by anesthesia of the mucous membrane in the upper nasal meatus. Possible mechanisms of this, probably reflex, phenomenon are discussed.

Theta (RSA) activity in the brain of the turtle.

The existence of a synchronizing system generating theta (RSA) activity of an average frequency of 4 Hz has been demonstrated in the brain of the turtle Testudo Graeca. Three brain structures probably participate in the activity--the septum, amygdala and hippocampus. The septal region seems to play a leading role in this complex--lesions in this region abolished the generation of theta activity in 71% of experiments. This synchronizing system is functionally coupled with the olfactory generator of electrographic respiratory response (ERR), which is brought into activity by nasal air flow. This coupling can play a role in genesis of epileptic electrographic activities not only in the turtle, but also in phylogenetically higher species.

Correlation of the macrogram and the microgram of the penicillin focus in turtle (Testudo) cerebral cortex. Localization of the capillary microelectrode tip with Pontamine Sky Blue 6BX.

Localization of the tip of the recording microelectrode with Pontamine Sky Blue 6BX introduced into the tissue iontophoretically was used to study the relationship of the morphological type of the neurone to a given type of elecrographic activity during the epileptic focal discharge. Paroxysmal depolarization shifts (PDSs) and short bursts of spikes in the negative phase of the focal discharge were found to be related to cells of the pyramidal type. Conversely, ovoid cells were active only in quiescent intervals and were inhibited throughout the whole duration of the focal discharge.

The effect of dexphenmetrazine and acetyldexphenmetrazine upon epileptic electrographic activities in the brain of the turtle.

The effect of acetyldexphenmetrazine (ADP) and dexphenmetrazine (DP) on normal and epileptic electrographic activities in the cortical and thalamic structures of the turtle brain were studied in curarized and artificially ventilated animals. Both drugs almost exclusively influenced cortical activities. The effect of low doses of ADP and DP was similar--they desynchronized cortical activity and suppressed the activity of a cortical penicillin focus. They also elevated the cortical response to optic stimuli. Higher doses of ADP continued to suppress both normal and epileptic cortical activities. Higher doses of DP had a two phase effect with enhancement of epileptic activity in the first phase. Continuous trains of theta activity appeared after low doses of ADP and very often after both low and high doses of DP. The findings are discussed in terms of comparative physiology of the brain.

Influence of nasal respiration upon normal EEG and epileptic electrographic activities in frog and turtle.

The electrographic respiratory response (ERR) was elicited by nasal air flow in the brain of the frog and turtle. It had the shape of a spindle of high voltage rhythmic activity and was propagated from the olfactory bulb predominantly into the ipsilateral hippocampal region in the frog and into the pyriform cortex in the turtle. In both animals, thalamic propagation of the ERR was also found. In both animals epileptic electrographic phenomena, were enhanced, created by local penicillin application. In the turtle epileptic electrographic manifestations were also elicited in the intact brain by simple nasal air insufflation. Diazepam (intraperitoneal administration) had no effect either on the ERR or on its triggering effect on epileptic phenomena. The possible physiological and pathophysiological interpretations of these findings are discussed.

Thalamocortical relations in the brain of the frog, Their role in the genesis of epileptic electrographic phenomena.

The existence of a thalamocortical reverberating circuit between the dorsal thalamic and primordial hippocampal structures could be proved in the brain of the frog (Rana temporarial) by evoking recruiting potentials. Unlike the turtle, this circuit does not take part in the genesis of electrographic phenomena in the corticogram of the frog under normal resting conditions. Spindle activity could not be observed in the EEG of curarized frogs. On the other hand, thalamic structures can influence paroxysmal susceptibility of the frog forebrain. The generation of the penicillin focus could be accelerated and paroxysmal electrographic activities elicited by iontophoretic application of penicillin into dorsal thalamic structures and/or rhythmic electric stimulation of this region. The features of thalamocortical cooperation in the frog and in the turtle have been compared.