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.     

Barrel cortex and whisker-mediated behaviors

Neural networks of the rodent barrel cortex are particularly tractable for developing a quantitative understanding of response transformations in a cortical column. A column in barrel cortex consists of approximately 10 compartments. Two thalamic input pathways, a sensory lemniscal one and sensorimotor paralemniscal one, are transformed to approximately 7 population outputs, each with distinct spatiotemporal response characteristics. Granular and supragranular layers are sites of segregated processing in lemniscal and paralemniscal pathways, whereas infragranular layers are sites of intracolumnar, lemniscal/paralemniscal integration. Individual thalamocortical connections are relatively weak, and a considerable fraction of thalamocortical afferents contributes to each sensory response. Intracortically, relatively few but strong synaptic connections contribute to sensory responses, and responses are rapidly terminated by inhibition. Overall cortical population activity is very low. Whiskers mediate a wide range of behaviors and many natural tactile behaviors occur very rapidly. Vibrissal object recognition can be size invariant and motion invariant and is based on the tactile 'Gestaltwahrnehmung' of shape.     

Interdigitated paralemniscal and lemniscal pathways in the mouse barrel cortex

Primary sensory cortical areas receive information through multiple thalamic channels. In the rodent whisker system, lemniscal and paralemniscal thalamocortical projections, from the ventral posteromedial nucleus (VPM) and posterior medial nucleus (POm) respectively, carry distinct types of sensory information to cortex. Little is known about how these separate streams of activity are parsed and integrated within the neocortical microcircuit. We used quantitative laser scanning photostimulation to probe the organization of functional thalamocortical and ascending intracortical projections in the mouse barrel cortex. To map the thalamocortical projections, we recorded from neocortical excitatory neurons while stimulating VPM or POm. Neurons in layers (L)4, L5, and L6A received dense input from thalamus (L4, L5B, and L6A from VPM; and L5A from POm), whereas L2/3 neurons rarely received thalamic input. We further mapped the lemniscal and paralemniscal circuits from L4 and L5A to L2/3. Lemniscal L4 neurons targeted L3 within a column. Paralemniscal L5A neurons targeted a superficial band (thickness, 60 μm) of neurons immediately below L1, defining a functionally distinct L2 in the mouse barrel cortex. L2 neurons received input from lemniscal L3 cells and paralemniscal L5A cells spread over multiple columns. Our data indicate that lemniscal and paralemniscal information is segregated into interdigitated cortical layers.     

Ethanol modulates AMPA-induced current responses of primary somatosensory cortical neurons.

This study examined the effect of ethanol on responses of primary somatosensory cortical neurons to AMPA. Thin (200-250 microns) brain slices were sectioned to include the primary somatosensory cortex of rats 6-15 days after birth. Visually-identified neurons were selected for whole-cell patch clamp recording and an eight-barrel drug pipet assembly was used to deliver test agents. Ethanol (5-100 mM) either positively or negatively modulated AMPA (100 microM)-induced current to varying degrees in approximately 70% of primary somatosensory cortical neurons. As revealed in layer V large pyramidal neurons, the outcome of an ethanol-induced modulation appeared to be age-dependent, the trend being one of potentiation in slices derived from younger rats (postnatal days 6-9) but one of attenuation in those derived from older animals (postnatal days 13-15). These findings indicate that ethanol at physiologically relevant concentrations modulates non-NMDA receptor-mediated responses of neurons in the rat primary somatosensory cortex.     

The background and evoked neuronal impulse activity of embryonic neurotransplant of somatosensory brain cortex in rats

The investigation was intended for studying the character of the background and evoked impulse activity of embryonic neurotransplant neurons 4 months after homotopical allotransplantation into the barrel field of somatosensory recipient's brain cortex of the rat. It is established, that the current average frequency of background impulse activity of transplant neurons is reduced in comparison with one of the control rats. It is shown that the evoked impulse activity of neurotransplant develops with the long latency than in somatosensory cortex of the control animals. Thus in patterns of the evoked activity of neurotransplant cells reactions, characteristic for the neurons of barrel field somatosensory recipient's cortex of control rats are registered: an increase of frequency of pulses' generating, or alternating of the activation and reduction periods of impulse frequency with its subsequent regeneration up to a pristine level.     

Tyrosinated alpha-tubulin changes following epileptogenic and non-epileptogenic lesions in rat brain cortex

The expression of the tyrosinated isoform of alpha-tubulin was monitored in rat frontal cortex, in order to investigate the neuronal plasticity changes occurring either in a mirror focus or in a deafferented area. A mirror focus was triggered by epidural implantation of a cobalt gelatin disk in the contralateral left somatosensory area (group one). A deafferented area was obtained by surgical removal of the left frontal cortex (group two). All animals including controls underwent EcoG recordings immediately before killing (45, 60, 90 days post surgery). The right frontal cortex was removed from all the animals and processed with Western blot method. EcoG recordings revealed a paroxysmal activity in epileptic rats, whereas in rats with frontal deafferentation and controls, EcoG activity was normal. A significant increase in tyrosinated alpha-tubulin expression was detected both in the mirror focus (group one) and the "non-epileptic" deafferented frontal cortex (group two) in comparison with controls (group three). The transcallosal deafferentation, which is involved in both epileptogenic and non-epileptogenic lesions, is supposed to play a role in the mechanism responsible for the plasticity responses recorded in the cortical areas studied.     

Increase in receptor binding affinity for nimodipine in the rat brain with permanent occlusion of bilateral carotid arteries

The permanent occlusion of bilateral common carotid arteries (2VO) in rats has been shown to cause progressive and long-lasting cognitive deficits which may be due to impairment of memory retention and/or memory recall process. To clarify the function of voltage dependent calcium channels and the receptor binding of nimodipine by chronic cerebral ischemia, we examined specific (+)-[3H]PN 200-110 binding and the effect of oral administration of nimodipine in brain regions and hearts of rats, at 2 weeks to 4 months after permanent 2VO. There was no significant difference in either dissociation constant (Kd) or maximal number of binding sites (Bmax) for (+)-[3H]PN 200-110 in the cerebral cortex, hippocampus, corpus striatum and thalamus between 2VO and sham rats. In addition, in vitro inhibitory effect of nimodipine on cerebral cortical (+)-[3H]PN 200-110 binding in 2VO rats was similar to that in sham rats. Compared to control rats, oral administration of nimodipine to both 2VO and sham rats at 2 months after permanent 2VO brought about a significant increase in Kd values of specific (+)-[3H]PN 200-110 binding in the cerebral cortex, hippocampus, thalamus and myocardium, and the increase in Kd values was much larger in brain regions of 2VO rats than sham rats. However, the increase in Kd values in the myocardium did not differ between 2VO and sham rats. This observation suggests an increased in vivo binding affinity for nimodipine in chronic ischemic brain. In conclusion, the present study has shown that oral administration of nimodipine may cause a greater occupation in vivo of 1,4-dihydropyridine (DHP) calcium channel antagonist receptors in brains of permanent 2VO rats than in sham rats. Thus, nimodipine may be pharmacologically effective in preventing brain dysfunction due to cerebral ischemia in vivo.     

Ontogeny of corticocortical projections of the rat somatosensory cortex.

Rhodamine-coated microspheres (RCMs) were injected into the primary somatosensory cortex (SI) of rats ranging in age from postnatal (PN) day 1 to adulthood. Ipsilateral corticocortical and callosal projections within the SI were identified as early as PN day 1. At the end of the first PN week, ipsilaterally projecting neurons located in sublayer VIb were the first to assume an adult-like pattern of connectivity. Injections at subsequent postnatal ages revealed that an adult pattern of lamination of ipsilateral corticocortical projections within the SI is established between PN weeks 2 and 3, comprising projection neurons from layers II/III, layer V, and sublayer VIb. Therefore, local interactions in the rat SI are mediated not only by pyramidal neurons of layers III and V, derived from the cortical plate, but also by a subpopulation of ontogenetically older neurons located in the sublayer VIb, which may correspond to the subplate neurons of other species. Overall, these results suggest the existence of three independent short-range corticocortical systems of projections within the rat SI, which differ in terms of the laminar distribution and ontogenetic origin of their cells.     

Vibrissa Self-Motion and Touch Are Reliably Encoded along the Same Somatosensory Pathway from Brainstem through Thalamus

Active sensing involves the fusion of internally generated motor events with external sensation. For rodents, active somatosensation includes scanning the immediate environment with the mystacial vibrissae. In doing so, the vibrissae may touch an object at any angle in the whisk cycle. The representation of touch and vibrissa self-motion may in principle be encoded along separate pathways, or share a single pathway, from the periphery to cortex. Past studies established that the spike rates in neurons along the lemniscal pathway from receptors to cortex, which includes the principal trigeminal and ventral-posterior-medial thalamic nuclei, are substantially modulated by touch. In contrast, spike rates along the paralemniscal pathway, which includes the rostral spinal trigeminal interpolaris, posteromedial thalamic, and ventral zona incerta nuclei, are only weakly modulated by touch. Here we find that neurons along the lemniscal pathway robustly encode rhythmic whisking on a cycle-by-cycle basis, while encoding along the paralemniscal pathway is relatively poor. Thus, the representations of both touch and self-motion share one pathway. In fact, some individual neurons carry both signals, so that upstream neurons with a supralinear gain function could, in principle, demodulate these signals to recover the known decoding of touch as a function of vibrissa position in the whisk cycle.     

Effect of vibrissae removal on the defensive behavior of rats in early ontogeny

Influence of restricted sensory afferentation in rats forming of defensive reactions was studied by vibrissectomy from 9 to 20 day of postnatal ontogeny. Defensive withdrawal reaction in response to touch from 10 to 18 day, duration of freezing on 20 day, "open field" behavior on 25 day were measured. Intensity of withdrawal reactions, freezing duration, flight reaction and emotionality in "open field" were lower in vibrissectomized rats with comparison to control.     

Transneuronal induction of the highly sialylated isoform of the neural cell adhesion molecule following nerve injury

The polysialylated, embryonic form of the neuronal cell adhesion molecule (PSA-NCAM) is known to participate in a whole series of synaptic rearrangements even in adult animals. The possible role of this molecule in neuroplastic changes of the adult rat somatosensory cortex induced by unilateral transection of the infraorbital branch of the trigeminal nerve was studied with PSA-NCAM immunostaining at light microscopic level. Two- and three-month-old CFY albino rats were sacrificied on days 1, 4, 6, 14 and 21 following operation and PSA-NCAM immunoreaction was examined at three levels of the vibrissa-cortex neuraxis, namely, in the principal nucleus of the trigeminal nerve, in the ventral posteromedial nucleus of the thalamus and in the somatosensory cortex. The lower levels of the neuraxis remained free of PSA-NCAM labeling, similarly to control, intact animals. However, a large number of scattered small neurons became PSA-NCAM immunoreactive in layers IV-VI on both ipsi- and contralateral sides of the somatosensory cortex from day 6 onwards, suggesting a possible transynaptic regulation of NCAM sialylation state.     

Extra-lemniscal afferent projections of dorsal spinal cord nuclei to the ventrobasal nuclear complex structure in the contralateral optic thalamus

It has been found that section of half the midbrain tegmentum in cats failed to prevent the afferent somatosensory projections from the foreleg to the ventrobasal nuclear complex of the contralateral thalamus. Specific evoked responses to the stimulation of the contralateral foreleg were recorded in this structure. These specific EP have the same latency as "lemniscal responses" (4-5 ms) and diminish the amplitude and duration of both components of the responses. Simultaneously, we have observed terminal axonal degeneration into the ventrobasal nuclear complex of the thalamus 5-7 days after the section of the contralateral midbrain tegmentum, using the electron microscopy method. All the results obtained indicate that the dorsal column nuclei have extra-lemniscal afferent connections with ventrolateral nuclear complex of the contralateral thalamus. These connections ascend in the back parts of the brainstem ipsilaterally to the corresponding pair of the dorsal column nuclei and rostrally to the midbrain on the contralateral side.     

The effect of vibrissa deprivation pattern on the form of plasticity induced in rat barrel cortex

Plasticity was induced in the barrel cortex of adolescent rats by depriving every second vibrissa on the contralateral vibrissa pad.This produced a chessboard pattern of barrels in the cortex where each barrel receiving its principal input from a spared vibrissa was surrounded by barrels for which the principal vibrissa had been deprived and conversely, each barrel receiving its principal input from a deprived vibrissa was surrounded by barrels for which the principal vibrissa had been spared. After 7 days' deprivation, responses to the regrown vibrissae were depressed in layers II/III (49% of control levels) and IV (60%). Depression was far greater than that seen with "all vibrissa" deprivation, suggesting that activity in the spared vibrissae accentuated the depression of the deprived vibrissae. Depression was not due to subcortical changes as thalamic Ventral Posterior Medial (VPM) responses to deprived vibrissa were unchanged. The short latency responses in layer IV (5-7 ms) were unaffected by deprivation, but the number of cells responding at intermediate latencies (8-13 ms) was markedly reduced (to 66% of control). Potentiation of the spared vibrissa response was substantial in the near side of the neighbouring barrel (2.2-fold increase in layers II/III, 2.9-fold in layer IV) but had not spread to the far side after 7 days' deprivation. Sparing multiple vibrissae may increase the rate of potentiation since 7 days is insufficient time for potentiation in single vibrissa spared animals. Potentiation was not due to subcortical changes as thalamic VPm responses to the spared vibrissa were normal. However, in the spared barrel the response latency decreased by 1-2 ms. Only the cells responding at short latency exhibited potentiated responses (39% increase) suggesting that some thalamocortical plasticity is still possible at P28-35. These results show that chessboard pattern deprivation is capable of inducing substantial plasticity over a wide area of barrel cortex. All the major forms of plasticity seen with other vibrissa deprivation patterns were present, although no other single deprivation pattern studied so far causes the complete repertoire seen with chessboard deprivation.     

Effect of chronic morphine exposure on response properties of rat barrel cortex neurons.

Chronic exposure to morphine can impair performance in tasks which need sensory processing. Using single unit recordings we investigate the effect of chronic morphine exposure on the firing properties of neurons in layers IV and V of the whisker-related area of rat primary somatosensory cortex. In urethane-anesthetized animals, neuronal activity was recorded in response to principal and adjacent whisker deflections either stimulated independently or in a conditioning test paradigm. A condition test ratio (CTR) was calculated for assessing the inhibitory receptive field. In layer IV, chronic morphine treatment did not change the spontaneous discharge activity. On responses to principal and adjacent whisker deflections did not show any significant changes following chronic morphine exposure. The magnitude Off responses to adjacent whisker deflection decreased while its response latency increased. In addition, there was a significant increase in the latency of Off responses to principal whisker deflection. CTR did not change significantly following morphine exposure. Layer V neurons, on the other hand, did not show any significant changes in their spontaneous activity or their evoked responses following morphine exposure. Our results suggest that chronic morphine exposure has a subtle modulatory effect on response properties of neurons in barrel cortex.     

Effect of Neonatal Epileptic Attacks on the Activity of Neocortical Neurons

Using the flurothyl model of neonatal epilepsy, we found that the sensitivity to a proepileptic agent (blocker of inhibitory synaptic transmission, bicuculline) is higher in slices of the somatosensory cortex of 80- to 90-dayold rats subjected preliminarily, within the neonatal period, to induction of epileptic attacks, as compared with those from control rats. The interictal-like seizure activity (extracellular recording from layer 2 of the neocortex) evoked by bicuculline applications developed in these cases with a noticeably greater probability.     

Whisker plucking alters responses of rat trigeminal ganglion neurons

Whisker plucking in developing and adult rats provides a convenient method of temporarily altering tactile input for the purposes of studying experience-dependent plasticity in the somatosensory cortex. Yet, a comprehensive examination of the effect of whisker plucking on the response properties of whisker follicle-innervating trigeminal ganglion (NVg) neurons is lacking. We used extracellular single unit recordings to examine responses of NVg neurons to controlled whisker stimuli in three groups of animals: (1) rats whose whiskers were plucked from birth for 21 days; (2) rats whose whiskers were plucked once at 21 days of age; and (3) control animals. After at least 3 weeks of whisker re-growth, NVg neurons in plucked rats displayed normal, single whisker receptive fields and could be characterized as slowly (SA) or rapidly adapting (RA). The proportion of SA and RA neurons was unaffected by whisker plucking. Both SA and RA NVg neurons in plucked rats displayed normal response latencies and angular tuning but abnormally large responses to whisker movement onsets and offsets. SA neurons were affected to a greater extent than RA neurons. The effect of whisker plucking was more pronounced in animals whose whiskers were plucked repeatedly during development than in rats whose whiskers were plucked once. Individual neurons in plucked animals displayed abnormal periods of prolonged rhythmic firing following deflection onsets and aberrant bursts of activity during the plateau phase of the stimulus. These results indicate that whisker plucking exerts a long-term effect on responses of trigeminal ganglion neurons to peripheral stimulation.     

Whisker plucking alters responses of rat trigeminal ganglion neurons

Whisker plucking in developing and adult rats provides a convenient method of temporarily altering tactile input for the purposes of studying experience-dependent plasticity in the somatosensory cortex. Yet, a comprehensive examination of the effect of whisker plucking on the response properties of whisker follicle-innervating trigeminal ganglion (NVg) neurons is lacking. We used extracellular single unit recordings to examine responses of NVg neurons to controlled whisker stimuli in three groups of animals: (1) rats whose whiskers were plucked from birth for 21 days; (2) rats whose whiskers were plucked once at 21 days of age; and (3) control animals. After at least 3 weeks of whisker re-growth, NVg neurons in plucked rats displayed normal, single whisker receptive fields and could be characterized as slowly (SA) or rapidly adapting (RA). The proportion of SA and RA neurons was unaffected by whisker plucking. Both SA and RA NVg neurons in plucked rats displayed normal response latencies and angular tuning but abnormally large responses to whisker movement onsets and offsets. SA neurons were affected to a greater extent than RA neurons. The effect of whisker plucking was more pronounced in animals whose whiskers were plucked repeatedly during development than in rats whose whiskers were plucked once. Individual neurons in plucked animals displayed abnormal periods of prolonged rhythmic firing following deflection onsets and aberrant bursts of activity during the plateau phase of the stimulus. These results indicate that whisker plucking exerts a long-term effect on responses of trigeminal ganglion neurons to peripheral stimulation.     

Organization of the Connections between the Parietal Associative Zone and the Primary Sensory Zones in the Cat Neocortex

In acute experiments on cats, we studied the impulse activity of 262 neurons of the parietal associative zone (PAZ, field 5). Among them, 129 cells [100 silent units and 29 units generating background activity (BA)] were identified as output neurons, while 133 cells with the BA were interneurons of the intrinsic cortical neuronal circuits. Electrical stimulation of the primary visual, auditory, or somatosensory cortices evoked no impulse responses in silent output PAZ neurons, while output neurons with the BA and interneurons (more than 65 and 80% of the cell units, respectively) generated clear responses (more frequently, phasic). Stimulation of the auditory and visual cortices exerted mostly inhibitory effects, while stimulation of the somatosensory cortex provided mostly excitatory influences. The ratios of neurons generating primary excitatory and inhibitory responses to stimulation of the visual, auditory, and somatic cortices were 0.3:1, 0.6:1, and 3.2:1, respectively. More than 95% of the field-5 neurons were influenced from the primary sensory zones via di- and/or polysynaptic pathways. Monosynaptic excitatory inputs from the visual cortex were identified for 3.8% of interneurons and 6.9% of output PAZ neurons; for the auditory cortical inputs, the respective figures were 1.7 and 3.5%. Monosynaptic connections with the somatic cortex were found only for 4% of the interneurons under study. It has been concluded that interaction of heteromodal signals coming to the PAZ via the corticopetal and associative inputs occurs on neurons of all the cortical layers.     

Ontogenesis of the spine-free initial zone of apical dendrites; studies in cortical pyramidal cells of albino rat]

1. In Golgi-Cox-impregnated coronal sections of albino rat brains at 1, 4, 26, 24, 30, 60 and 90 days it is presented the evolution of the spine-less, bare initial zone ("nude zone", NZ) at the proximal apical main dendrites of the layer V pyramidal neurons in the somatosensory and anterior limbie cortex. The quantitative results are analyzed by statistical methods. 2. The NZ is comprehended as a morphological correlate of the endodendritic neuroplasmic flow (Weiss 1944, Globus, Lux and Schuberl 1968, Kreutzberg 1973). The observed changes of the percental frequency and the average length of NZ increases rapidly. 3. The NZ occurs at first in the (12th) 16 postnatal day, thus in a time, when the organs of hearing and the eyes are differentiated completely. Between 16th and 24th day the percental frequency as well as the longitude of NZ increases. During this time the rats will be independent of the mother animals. With the full differentiation of the urogenital tract and especially with the sexual maturity the percentage frequency of NZ increases only at pyramidal cells in the anterior limbie cortex between 24th and 60th day. During 3rd month the NZ is occuring percental more frequently in the anterior limbic cortex than in the somatosensory cortex. At this time the average length of NZ is shorter in the limbic cortex. 4. As to the enriched, vivid movement of the animals and the playing impulse of the young rats the average length of NZ will be extended at pyramidal neurons in the somatosensory cortex during 2nd month, as well as the pattern of spine distribution will be changed along apical dendrites (Schlerhorn, unpublished). During the following (3rd) month the NZ will be shorteded in the somatosensory cortex, obviously caused by new formation of spines at the proximal main dendrites. 5. These newly formed spines in the initial zone of apical dendrites may be inhibitory spines. The inhibitory spines are stained only when using the mercury chromate impregnation according to Golgi-Cox, but not when using the silver chromate methods according to Golgi-Kopsch or Golgi-Bubenaite. The different tingibility of these spines by different Golgi techniques is discussed by Doedens, Nagel and Schierhorn (1974). The pyramidal neurons in the somatosensory cortex possess a longer average length of NZ (Lnz = 7,3[mum]) than the pyramidal cells in the anterior limbic cortex (Lnz = 6.2[mum]). As to NZ the differences between silver and mercury chromate stained pyramidal neurons are greater in the somatosensory cortex than in limbic cortex (see Tab. 7). Therefore we assume that there are in the initial zone of somatosensory pyramidal neurons more inhibitory spines than at the pyramidal neurons in the anterior limbic cortex. 6. The regional differences in the percentual frequency and in the average length of NZ between somatosensory and limbic cortex are new identifying marks of architectonic differentiation of the pyramidal neurons in cortical regions of phylogenetically different ages.     

Interrelations of the cerebral hemispheres in the cat in early stages of ontogeny

Multiple recording of transcallosal responses (TCRs) from different cortex areas has been carried out by means of acute experiments with immobilized and anesthetized kittens at the age of 1 to 30 days after birth. Homotopical TCRs in kittens at the age of 2-15 days appear earlier, are presented wider and reveal features of a greater maturity configuration and of amplitudinal-temporal parameters in association zone (parietal and sensorimotor) in comparison with projection zones (somatosensory, visual and auditory). Interhemispheric interrelations in association cortex of kittens are carried out not only by means of callosal but extracallosal system. In the course of animal developing in the parietal cortex the drain of the surface-positive oscillation moves from V to III layer and the drain of the surface-negative deviation remains at the level of II-III layers. The late component is registered up to the depth of III-IV layers, having the drain in I-II layers. In sensorimotor cortex the surface-negative oscillation has the drain in I-II layers, surface-positive--in III and V--VI layers. The interhemispheric asymmetry emerging from the moment of responses appearance is peculiar to TCRs of projection and association zones. In the first month of the postnatal development the asymmetry of positive and negative TCR oscillation amplitude has an individual character in sensorimotor cortex and a specific one--in parietal. The temporal parameters of TCR in association areas of the left hemisphere cortex are significantly shorter than of the right one. The data given testify to the possibility of interhemispheric interrelation realization and the presence of interhemispheric asymmetry in cat's brain on the early stages of postnatal ontogenesis.