Cortical Somatosensory Neurons in WAG/Rij Rats Transform Firing Evoked by Simulation of Posterior Thalamic Nucleus from Tonic to Phasic at Age of 6 Months.

Functional peculiarities of paralemniscal subdivision of the thalamocortical system were examined in normal Wistar and in WAG/Rij rats genetically prone to absence epilepsy. In 6-7-month-old WAG/Rij characterized by developed epileptic activity, the response of cortical somatosensory neurons to single electrical stimulation of the posterior thalamic nucleus was phasic, whereas in normal Wistar rats, similar reaction was tonic. The study views this phasic response as neural equivalent of spike-wave discharges known as typical EEG symptom of absence epilepsy.

The Responses of Neurons of the Somatosensory Cortex to Stimulation of the Posterior Thalamus (PO) in WAG/Rij Rats Genetically Predisposed to Absence Epilepsy.

In genetically predisposed WAG/Rij rats and healthy Wistar rats, we studied functioning of the paralemniscal region of the thalamo-cortical system. The responses of neurons of the somatosensory cortex to single electrical stimulation of the posterior nucleus of the thalamus were recorded in two- to three-monthold rats within the period when the epileptic activity was not developed. We revealed lower number of shortterm inhibitory responses in WAG/Rij rats as compared to Wistar rats. This may create preconditions for the spreading of spike-wave activity in the somatosensory cortex, which is an electrophysiological sign of absence epilepsy.

The Influence of Pre- and Postnatal Factors on Early Behavior Formation.

The maternal impact on the early behavioral responses in pups was studied in cross-fostering experiments with the newborn Wistar rats (the primiparous females were fostering the pups born to the females parturiated for the second time and vise versa). The maternal experience had a significant influence on the function development in both pre- and postnatal periods. Specific features of prenatal ontogeny of pups born by experienced females resulted in further, more stable development of the early behavioral responses. In the postnatal period, the maternal experience determined synchronization of the behavioral responses, which promoted the formation of the functional systems important for the newborn survival.

Compensatory Changes in the Brain Dopaminergic System of WAG/Rij Rats Genetically Predisposed to Absence Epilepsy.

Involvement of the brain dopaminergic system in the age-related dynamics of absence epilepsy in WAG/Rij rats was examined by histological, immunohistochemical, and electrophysiological (EEG) methods. We revealed reduced expression of dopamine receptors in various brain structures prior to first manifestations of the disease (at the age of 1-3 months), reduced density of neurons in the center of nigrostriatal system (substantia nigra pars compacta) in 10-month-old rats in comparison with 1-month-old rats, and positive correlation between neural density in the substantia nigra and intensity of epileptic activity in EEG. It is hypothesized that loss of dopaminergic neurons and reduced nigrostriatal dopaminergic innervation of the brain could prevent the development of absence epilepsy in WAG/Rij rats.

[INFLUENCE OF THE MOTHERHOOD EXPERIENCE ON THE FORMATION OF SPECIES-SPECIFIC BEHAVIOR OF THE OFFSPRING IN EARLY ONTOGENY].

The effect of maternal experience on the maturing of early behavior reactions and species-specific defensive behavior (dark preference reaction) in the offspring of Wistar rats was investigated. We found differences between maternal behavior of primiparous females and the same females after second parturi- tion. The behavior of experienced female is characterized by maintenaning a more comfortable state in the nest, and more care for the offspring. The study of the dynamic of behavior in the offspring of primiparous females revealed the disappearance of the correlation between the timing of opening the eyes and the appearance of the first offspring behavioral responses, which is a negative factor for the formation of adaptive behavior in ontogenesis. A violation of the development of a species-specific defensive behavior (dark preference reaction) was found in the offspring of naive females. The results indicate a positive in- fluence of motherhood experience on the formation of functions of their offspring.

Changes in sensitivity of cholinoceptors and adrenoceptors during transhemispheric cortical reorganisation in rat SmI.

The reorganisation of primary somatosensory cortex that occurs after lesioning the corresponding cortex of the contralateral hemisphere in rat has been termed, 'transhemispheric cortical reorganisation'. Cholinergic and noradrenergic innervations are hypothesized to be involved in cortical plasticity. The present study investigated the change in responses of somatosensory neurones in the hindpaw representation area to muscarinic cholinoceptor and beta-adrenoceptor receptor stimulation, by iontophoretic application of acetylcholine, noradrenaline, propranolol and atropine, during the process of transhemispheric cortical reorganization at 3-4 days and at 20-21 days after lesioning the corresponding area in the contralateral hemisphere. Most neurones in control rats showed excitatory atropine-sensitive responses to acetylcholine, and inhibitory propranolol-sensitive responses to noradrenaline. A marked reduction in neurones exhibiting muscarinic responses (from 69% to 22%) and beta-noradrenoceptor-mediated responses (from 62% to 24%) were seen in rats 3-4 days post lesion. The proportion of neurones responding had recovered by 3 weeks but the direction of the responses had changed with muscarinic response becoming predominantly inhibitory and beta-noradrenoceptor responses predominantly excitatory. It is concluded that transhemispheric cortical reorganization involves both receptor types and that the reciprocal changes at different stages after injury maintain cortical plasticity.

Lesions of the nucleus basalis magnocellularis do not alter the proportions of pirenzepine- and gallamine-sensitive responses of somatosensory cortical neurones to acetylcholine in the rat.

The effects of S-alpha-amino-3-hydroxy-4-isoxozolepropionic acid (AMPA) lesions of the nucleus basalis magnocellularis on the M1/M2 nature of the responses of somatosensory cortical neurones to acetylcholine (ACh) in Sprague-Dawley rats were investigated by iontophoretic application and extracellular single unit recording. The responses were characterised using pirenzepine, an M1 receptor antagonist, and gallamine, an M2 antagonist. Eighty two neurones in control and 94 neurones in lesioned animals were studied. In control animals, 37% of responses to ACh were sensitive to pirenzepine, gallamine or to both antagonists. This increased to 62% in lesioned animals, the proportions of pirenzepine- and gallamine-sensitive responses remaining unchanged. These results provide the first electrophysiological confirmation that both pirenzepine- and gallamine-sensitive (M1 and M2) receptors occur postsynaptic to afferent cholinergic terminals and that their postsynaptic stimulation may produce both inhibition and excitation.

Sensory information--the major factor of ontogeny.

On the basis of their own data authors postulate that the increase in sensory input during early ontogeny results in a delay in the development of the sensory systems formed earlier. In connection with this, the sensory basis of behavioral patterns becomes ineffective, causing their reorganization and the appearance of new forms of behavior. Limitation of sensory input during during the critical periods of development stimulates the accelerated manifestation of behavioral patterns. However, this acceleration also has long-lasting negative effects - alterations in the process of learning and memory in adult animals.

Reduction of GABAergic transmission and alterations in behavior after 6-OHDA treatment of rats.

We studied the effects of neonatal administration of 6-hydroxydopamine (6-OHDA) upon gamma-aminobutyric acid (GABA) and noradrenergic neurotransmission in the developing rat brain. After 6-OHDA administration tyrosine hydroxylase (TH) immunolabelling revealed more than 70% loss of catecholaminergic terminals in cortex. Glutamic acid decarboxylase (GAD) immunolabelling showed that the intensity of staining and the density of labelled terminals were decreased by approximately 50% in the prefrontal cortex of 6-OHDA treated animals, but in visual and somatosensory zones there was no difference between lesioned and control cortex. The open field test revealed an altered development of the searching activity after neonatal 6-OHDA injections. A significant difference was found between 6-OHDA treated and control rats in searching, orienting and skills performance. Our results indicate that the behavioral changes observed in young rats after 6-OHDA treatment may be reflections not only of reduced catecholaminergic transmission but also of GABAergic disturbance, occurring in the frontal cortex.

An iontophoretic study of the effects of alpha-amino-hydroxy-5-methyl-4-isoxazole propionic acid lesions of the nucleus basalis magnocellularis on cholinergic and GABAergic influences on frontal cortex neurones of rats.

Unilateral lesions of the nucleus basalis magnocellularis (NBM) produced by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid in rats caused, 8-10 weeks after the lesion, a 94% reduction in cortical acetylcholinesterase fibres and reduced activities of acetylcholinesterase and choline acetyltransferase by 70-80% in the frontal cortex ipsilateral to the lesion. In anaesthetized unlesioned control rats, iontophoretic administration of acetylcholine and carbachol produced atropine-sensitive inhibition and excitation of frontal cortical neurones, effects similar to those produced by electrically stimulating the NBM. The lesion reduced cortical neuronal firing rates but increased the percentage and sensitivity of neurones responding to acetylcholine, the predominant response changing from inhibition to excitation; response duration increased but latency was unaffected. The size of the response of individual neurones to carbachol, but not the percentage of sensitive neurones, was also increased in lesioned animals. The proportion of neurones responding to bicuculline and their individual sensitivities were increased by the lesion, suggesting that the lesion increased GABAergic tone; responses to glutamate were unchanged. The lesion did not affect the proportion of neurones in which acetylcholine modulated neuronal responses but reversed the nature of the modulation to predominantly excitatory; excitation was the predominant response to electrical forepaw stimulation in unlesioned control animals. This suggests a possible interaction between GABAergic and cholinergic mechanisms in selective attention and processing of cognitive information. Acute administration of di-isopropyl fluorophosphate to unlesioned animals significantly increased the number of frontal cortical neurones responding to acetylcholine, without affecting individual neuronal sensitivity or responses to carbachol and glutamate. The similarity of these effects to those of acetylcholine in lesioned animals suggests that the increased sensitivity to acetylcholine in the latter was due to loss of acetylcholinesterase, enabling diffusion of acetylcholine to more distant neurones. However, acetylcholinesterase does not hydrolyse carbachol and therefore it is necessary to postulate a different post-synaptic mechanism to explain the lesion-induced increases in the sensitivities of individual neurones to carbachol and to acetylcholine; interpretation of experimental findings should take these two mechanisms into account.

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.