Enhancement of the antiepileptic efficacy of diazepam at electrical stimulation of the cerebellar cortex

The action of diazepam (0.5 and 1.5 mg/kg, i.v.) on epileptic foci induced by benzylpenicillin (10,000 IU/ml) applications onto thesulc. sygmoid post. was studied in acute experiments on cats. It is demonstrated that under conditions of preceding electrical stimulation of the cerebellar vermis, diazepam more significantly suppresses the epileptic activity than when it is administered to intact animals.     

Interaction between unit responses of the cat cerebellar cortex during paired stimulation of the forelimbs

Interaction between spike responses of 41 cerebellar cortical neurons to electrical stimulation of the two forelimbs with different intervals between stimuli were studied in cats anesthetized with chloralose and pentobarbital. The responsiveness of neurons with a phasic type of discharge to testing stimulation of the limb was reduced for 300–500 msec or longer after conditioning stimulation of the other limb. Interaction between the responses was less clear in neurons with a tonic type of response. Interaction was absent or was summating in character if the stimuli were applied at the same times. Only if the intertrial intervals were 50–150 msec was regular inhibition of the responses of tonic type to the testing stimulus observed. It is postulated that the nucleus of the inferior olive participates in the interaction between phasic unit responses during simultaneous stimulation of the two limbs or to stimulation separated by short intervals (under 30 msec). With longer intervals between stimuli, interaction between responses of either type is connected with involvement of the lateral reticular nucleus. In the process of interaction competitive relations may develop between responses caused by impulses reaching neurons of the cerebellar cortex along climbing and mossy fibers.     

Unit responses of the cerebellar cortex to stimulation of the vagus nerve and nerves of the limbs

Responses of 74 cerebellar cortical neurons to electrical stimulation of the vagus nerve and its gastric branches and also of the limb nerves were recorded extracellularly in experiments on rats anesthetized with chloralose and pentobarbital. Phasic and tonic unit responses were similar to all types of stimulation, but fewer neurons responded to stimulation of the vagus nerve than to stimulation of the limb nerves. Monosensory neurons responding only to visceral stimulation, were not found. Among cells giving a phasic response, some had a short and others a long latent period. The latent period of responses of all types was longer to vagal stimulation than to stimulation of the limb nerves. The maximal frequency of rhythmic responses to vagal stimulation was 8/sec, compared with 16/sec for stimulation of the limb nerves. Tonic responses of the neurons were excitatory, inhibitory, and mixed. The type of unit response could vary depending on the frequency and repetitiveness of the stimuli but was otherwise independent of the type of stimulation.N. I. Pirogov Vinnitsa Medical Institute. I. M. Sechenov Institute of Evolutionary Biochemistry and Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 4, No. 5, pp. 471–479, September–October, 1972.     

Pattern formation in the cerebellar cortex.

The cerebellar cortex is subdivided rostrocaudally and mediolaterally into a reproducible array of zones and stripes. This makes the cerebellum a valuable model for studying pattern formation in the vertebrate central nervous system. The structure of the adult mouse cerebellar cortex and the series of embryological events that generate the topography are reviewed.     

Analysis of evoked potentials of the cerebellar cortex

Evoked potentials (EP) of the cerebellar cortex in response to stimulation of peripheral nerves are characterized by a two-phase positive-negative oscillation of the potential having a latent period of 10–25 msec. The electropositive phase can contain up to three components. The latent period of component I comprises 3–9 msec. The latent period and amplitude of this component are distinguished by considerable stability, which indicates the predominant significance of presynaptic processes in its formation. The sign of component II changes at a depth of 500 µ (and more), which corresponds to the position of the granular cell layer. At this level there arises in the neurons a response with a latent period of 4–10 msec in the form of a group (3–10) of impulses with a frequency of up to 200 per sec. It is concluded that the granular cells participate in the formation of component II and partially participate in the formation of components I and III of the EP. Responses to stimulation of the nerves appear synchronously with the EP in 24% of responding Purkinje cells; they fall on the maximum electropositive deviation or component III of the EP. Microinjections of 1% strychnine into the cerebellar cortex cause an increase of EP amplitude; impulse activity of the neurons is intensified. This indicates participation of postsynaptic processes in the formation of EP. No shifts in the EP of the cerebellar cortex were observed after intracortical injection of 0.1% atropine.N. I. Pirogov Vinnitsa Medical Institute. Translated from Neirofiziologiya, Vol. 2, No. 4, pp. 429–433, July–August, 1970.     

Synaptic effects induced in efferent neurons of the parietal associative cortex of the cat by stimulation of the cerebellar nuclei

Properties of EPSP, evoked in efferent neurons of the parietal associative cortex by stimulation of the cerebellar nuclei, were studied in acute experiments on anesthetized and immobilized cats; intracellular recording was used. The neurons were identified by their antidromic activation after stimulation of the motor cortex, pontinen.n. proprii, or red nucleus. The effects of stimulation of the cerebellar nuclei were of oligo- and polysynaptic nature. The latencies of cerebellofugal EPSP correlated with the latencies of antidromic activation, and correlations were significant both in the cases when the effects of stimulation of separate efferent projections (cortico-cortical, cortico-pontine, or cortico-rubral) and the effects of stimulation of separate cerebellar nuclei were analyzed. The functional role of the efferent systems of the parietal associative cortex and significance of functional parameters of the neurons constituting these systems are discussed.Neirofiziologiya/Neurophysiology, Vol. 27, No. 3, pp. 190–198, May–June, 1995.     

Neurotrophic effects of PACAP in the cerebellar cortex

In the rodent cerebellum, PACAP is expressed by Purkinje neurons and PAC1 receptors are present on granule cells during both the development period and in adulthood. Treatment of granule neurons with PACAP inhibits proliferation, slows migration, promotes survival and induces differentiation. PACAP also protects cerebellar granule cells against the deleterious effects of neurotoxic agents. Most of the neurotrophic effects of PACAP are mediated through the cAMP/PKA signaling pathway and often involve the ERK MAPkinase. Caspase-3 is one of the key enzymes implicated in the neuroprotective action of PACAP but PACAP also inhibits caspase-9 activity and increases Bcl-2 expression. PACAP and functional PAC1 receptors are expressed in the monkey and human cerebellar cortex with a pattern of expression very similar to that described in rodents, suggesting that PACAP could also exert neurodevelopmental and neuroprotective functions in the cerebellum of primates including human.     

Aftereffect phenomena in neurons of the cerebellar cortex

The reactions of Purkinje cells (PC) of the cerebellar cortex during electrocutaneous stimulation of one of the extremities with different frequencies (from one stimulus in 10 sec to one to five stimuli per sec) were studied in experiments on cats. It was shown that the reactions to the first and subsequent stimuli were different. This indicates the presence of an aftereffect from the first stimulus. It is assumed that the variability of the responses of PC to infrequent stimuli is connected with changes in their functional state which develop in response to "spontaneous" cerebellopetal impulses, as well as to circulation of excitation in intracerebellar circuits. With an increase in the frequency of the stimuli, the changes in excitability induced by previous peripheral stimuli, not only in the reacting PC, but also in the whole neuronal network of the corresponding cerebellopetal pathway, evidently acquire paramount importance. The absence of a direct relationship between strong peripheral stimulation and the degree of the reactions of the PC may be due to the involvement of intermediate neurons both of the exciting and inhibitory type in the transmission of impulses at the level of the cerebellar cortex.N. I. Pirogov Vinnitsa Medical Institute. Translated from Neirofiziologiya, Vol. 2, No. 6, pp. 573–580, November–December, 1970.     

The myelination of the cerebellar cortex in the cat

Summary The myelination of the cerebellar cortex of the cat was investigated in 61 cats aged from 3 hrs post partum to two and a half years. The first myelinated fibers appear at the time of birth in the central medullary ray. Before the onset of myelination, all fibers reach a critical diameter of about 1 m. About the 14th day of life the number of oligodendrocytes in the prospective white matter increases markedly. Thereafter, the oligodendrocytes invade the inner granular layer. It therefore seems that the myelination of the cerebellar cortex proceeds from the central medullary ray towards the granular layer. At the 60th day of postnatal life, most of the afferent and efferent fiber systems are myelinated. These findings are discussed in relation to the development of function and the maturation of the electrical activity of the cerebellar circuit.Dedicated to Prof. Dr. H. Leonhardt in honour of his 60th birthdaySupported by the Deutsche Forschungsgemeinschaft (La 184/3)