The structural-functional characteristics of the rostral sections of the neocortex in Chiroptera]

Studies have been made on the connections of rostral neocortex in bats in order to reveal connections with the structures of the auditory sensory system the existence of which is indicated by evident specific responses to ultrasound in the form of synchronization reaction. It was shown that dorsolateral parts of the rostral neocortex receive topically organized projections from the thalamic nuclei VPL and VL. Connections with the auditory cortex and suprageniculate nucleus are not evident. Afferents of the medial wall of the rostral cortex originate from the thalamic nuclei MD and AM. Possible pathways of auditory afferentation to the dorso-lateral part of rostral neocortex are discussed.     

Role of the basal ganglia in the occurrence of paradoxical sleep dreams (hypothetical mechanism)

A hypothetical mechanism of the basal ganglia involvement in the occurrence of paradoxical sleep dreams and rapid eye movements is proposed. According to this mechanism, paradoxical sleep is provided by facilitation of activation of cholinergic neurons in the pedunculopontine nucleus as a result of suppression of their inhibition from the output basal ganglia nuclei. This disinhibition is promoted by activation of dopaminergic cells by pedunculopontine neurons, subsequent rise in dopamine concentration in the input basal ganglia structure. striatum, and modulation of the efficacy of cortico-striatal inputs. In the absence of signals from retina, a disinhibition of neurons in the pedunculopontine nucleus and superior colliculus allows them to excite neurons in the lateral geniculate body and other thalamic nuclei projecting to the primary and higher visual cortical areas, prefrontal cortex and back into the striatum. Dreams as visual images and "motor hallucinations" are the result of an increase in activity of definitely selected groups of thalamic and neocortical neurons. This selection is caused by modifiable action of dopamine on long-term changes in the efficacy of synaptic transmission during circulation of signals in closed interconnected loops, each of which includes one of the visual cortical areas (motor cortex), one of the thalamic nuclei, limbic and one of the visual areas (motor area) of the basal ganglia. pedunculopontine nucleus, and superior colliculus. Simultaneous modification and modulation of synapses in diverse units of neuronal loops is provided by PGO waves. Disinhibition of superioir colliculus neurons and their excitation by pedunculopontine nucleus lead to an appearance of rapid eye movements during paradoxical sleep.     

Characterization of factors regulating lamina-specific growth of thalamocortical axons

During development, most thalamocortical axons extend through the deep layers to terminate in layer 4 of neocortex. To elucidate the molecular mechanisms that underlie the formation of layer-specific thalamocortical projections, axon outgrowth from embryonic rat thalamus onto postnatal neocortical slices which had been fixed chemically was used as an experimental model system. When the thalamic explant was juxtaposed to the lateral edge of fixed cortical slice, thalamic axons extended farther in the deep layers than the upper layers. Correspondingly, thalamic axons entering from the ventricular side extended farther than those from the pial side. In contrast, axons from cortical explants cultured next to fixed cortical slices tended to grow nearly as well in the upper as in the deep layers. Biochemical aspects of lamina-specific thalamic axon growth were studied by applying several enzymatic treatments to the cortical slices prior to culturing. Phosphatidylinositol phospholipase C treatment increased elongation of thalamic axons in the upper layers without influencing growth in the deep layers. Neither chondroitinase, heparitinase, nor neuraminidase treatment influenced the overall projection pattern, although neuraminidase slightly decreased axonal elongation in the deep layers. These findings suggest that glycosylphosphatidylinositol-linked molecules in the cortex may contribute to the laminar specificity of thalamocortical projections by suppressing thalamic axon growth in the upper cortical layers.     

The role of the thalamus in the flow of information to the cortex

The lateral geniculate nucleus is the best understood thalamic relay and serves as a model for all thalamic relays. Only 5-10% of the input to geniculate relay cells derives from the retina, which is the driving input. The rest is modulatory and derives from local inhibitory inputs, descending inputs from layer 6 of the visual cortex, and ascending inputs from the brainstem. These modulatory inputs control many features of retinogeniculate transmission. One such feature is the response mode, burst or tonic, of relay cells, which relates to the attentional demands at the moment. This response mode depends on membrane potential, which is controlled effectively by the modulator inputs. The lateral geniculate nucleus is a first-order relay, because it relays subcortical (i.e. retinal) information to the cortex for the first time. By contrast, the other main thalamic relay of visual information, the pulvinar region, is largely a higher-order relay, since much of it relays information from layer 5 of one cortical area to another. All thalamic relays receive a layer-6 modulatory input from cortex, but higher-order relays in addition receive a layer-5 driver input. Corticocortical processing may involve these corticothalamocortical 're-entry' routes to a far greater extent than previously appreciated. If so, the thalamus sits at an indispensable position for the modulation of messages involved in corticocortical processing.     

Characterization of factors regulating lamina‐specific growth of thalamocortical axons

During development, most thalamocortical axons extend through the deep layers to terminate in layer 4 of neocortex. To elucidate the molecular mechanisms that underlie the formation of layer‐specific thalamocortical projections, axon outgrowth from embryonic rat thalamus onto postnatal neocortical slices which had been fixed chemically was used as an experimental model system. When the thalamic explant was juxtaposed to the lateral edge of fixed cortical slice, thalamic axons extended farther in the deep layers than the upper layers. Correspondingly, thalamic axons entering from the ventricular side extended farther than those from the pial side. In contrast, axons from cortical explants cultured next to fixed cortical slices tended to grow nearly as well in the upper as in the deep layers. Biochemical aspects of lamina‐specific thalamic axon growth were studied by applying several enzymatic treatments to the cortical slices prior to culturing. Phosphatidylinositol phospholipase C treatment increased elongation of thalamic axons in the upper layers without influencing growth in the deep layers. Neither chondroitinase, heparitinase, nor neuraminidase treatment influenced the overall projection pattern, although neuraminidase slightly decreased axonal elongation in the deep layers. These findings suggest that glycosylphosphatidylinositol‐linked molecules in the cortex may contribute to the laminar specificity of thalamocortical projections by suppressing thalamic axon growth in the upper cortical layers. © 2000 John Wiley & Sons, Inc. J Neurobiol 42: 56–68, 2000     

Functional topography of afferent projections of the horizontal division of the nucleus of the diagonal band in the dorsolateral neocortex of the cat

EPs recording under Nembutal anaesthesia during stimulation of the medial section of the horizontal part of the diagonal band nucleus (HNDB) shows a wide spreading of HNDB afferentation over the neocortex: from the frontal area to the medial and some posterior parts of the auditory, parietal areas and Ep zone, with the least activation of the latter three regions and activation increasing intensity correspondingly in the somatic zones II, I (SII, SI), motor and frontal cortex. Such reduction of signals flow intensity oriented both in caudal and ventral directions of the cortex goes with foci of maximal activity of these signals in the motor, parietal areas and zones of representation of various body parts in SI and SII. Traits of similarity and differences of signal's projections in the neocortex from HNDB and thalamic relay nuclei have been revealed. A hypothesis is substantiated on different mechanisms underlying peculiarities of influences of these subcortical nuclei on the cortex depending on the type of their afferent-neuronal links in the latter and their functional role in the brain activity.     

Analysis of long cortical evoked potentials

Evoked potentials arising in the motor cortex in response to its direct stimulation (dendritic and slow negative potentials), to stimulation of the ventrolateral (primary response) and intralaminar (nonspecific response) thalamic nuclei, and to stimulation of the pyramidal tracts (antidromic response), and also postsynaptic responses of neurons corresponding to them were studied in acute experiments on curarized cats. Evoked potentials arising in response to direct cortical stimulation and also to stimulation of the specific and nonspecific thalamic nuclei and pyramidal tracts were recorded from the same point of the motor cortex, and the corresponding intracellular responses were recorded from the same neuron. Slow negative potentials arising under these conditions of stimulation and the IPSPs corresponding to them were shown to have an identical time course. The results show that slow negative potentials are a reflection of hyperpolarization of pyramidal neurons. It is suggested that the individual components of responses evoked by direct stimulation of the cortex and thalamic nuclei have a common genesis.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 14, No. 2, pp. 115–121, March–April, 1982.     

Organization of the thalamic and cortical projections of the cat neostriatum]

The investigation has demonstrated that in the cat the nucleus caudatus and the putamen are projected on the cortex and thalamic nuclei of the ipsilateral hemisphere according to a certain topical principle characterized by both similarity in localization of projections of these two structures of the neostriatum and their difference. On the one hand, to the same fields of the cortex and the thalamic nuclei fibres from both structures of the neostriatum go, and on the other hand--a number of cortical zones and thalamic nuclei get projections either from the nucleus caudatus or from the putamen only. Owing to a certain organization of the connections studied, it is possible to consider them as the base of functional heterogeneity of the basal ganglia. Over-lapping of the cortical and thalamic projections of the nucleus caudatus and the putamen might explain common striatal effects on behavioral reactions.     

The thalamus in the motor system.

The ventrolateral (VL) and anterior (VA) are the main thalamic relay for cerebellar and pallidal efferents going to the motor cortex. Four aspects of the function of these nuclei are briefly considered. (1) It is well known that these thalamic structures are not a simple relay on the way to the motor cortex, but that they have a gating function for the cerebellar afferents. The gating mechanism is active during slow-wave sleep, with deafferentation and with the use of various anesthetics. Possibly, it might play a role in the central organization of movement. (2) The organization at the unitary level of the projections between VL and motor cortex is examined and their role in the command of motor synergies through the motor cortex is strongly suggested. (3). It appears that unitary activity of VL neurons is not only related to movement but also to postural changes associated with movement. (4) The sensory input to VL nucleus is briefly analyzed. The inefficacy of exteroceptive stimulation in awake animals, in contrast with the effect of the same stimulation in anesthetized preparations, is discussed.     

Thalamic relay functions and their role in corticocortical communication: generalizations from the visual system.

All neocortical areas receive thalamic inputs. Some thalamocortical pathways relay information from ascending pathways (first order thalamic relays) and others relay information from other cortical areas (higher order thalamic relays), thus serving a role in corticocortical communication. Most, possibly all, afferents reaching thalamus, ascending and cortical, are branches of axons that innervate lower (motor) centers, so that thalamocortical pathways can be viewed generally as monitors of ongoing motor instructions. In terms of numbers, the thalamic relay is dominated by synapses that modulate the relay functions. One of the roles of these modulatory pathways is to change the transfer of information through the thalamus, in accord with current attentional demands. Other roles remain to be explored. These modulatory functions can be expected to act on corticocortical communication in addition to their action on ascending pathways.     

Spatiotemporal dynamics of cortical sensorimotor integration in behaving mice

Tactile information is actively acquired and processed in the brain through concerted interactions between movement and sensation. Somatosensory input is often the result of self-generated movement during the active touch of objects, and conversely, sensory information is used to refine motor control. There must therefore be important interactions between sensory and motor pathways, which we chose to investigate in the mouse whisker sensorimotor system. Voltage-sensitive dye was applied to the neocortex of mice to directly image the membrane potential dynamics of sensorimotor cortex with subcolumnar spatial resolution and millisecond temporal precision. Single brief whisker deflections evoked highly distributed depolarizing cortical sensory responses, which began in the primary somatosensory barrel cortex and subsequently excited the whisker motor cortex. The spread of sensory information to motor cortex was dynamically regulated by behavior and correlated with the generation of sensory-evoked whisker movement. Sensory processing in motor cortex may therefore contribute significantly to active tactile sensory perception.     

The early topography of thalamocortical projections is shifted in Ebf1 and Dlx1/2 mutant mice

The prevailing model to explain the formation of topographic projections in the nervous system stipulates that this process is governed by information located within the projecting and targeted structures. In mammals, different thalamic nuclei establish highly ordered projections with specific neocortical domains and the mechanisms controlling the initial topography of these projections remain to be characterized. To address this issue, we examined Ebf1(-/-) embryos in which a subset of thalamic axons does not reach the neocortex. We show that the projections that do form between thalamic nuclei and neocortical domains have a shifted topography, in the absence of regionalization defects in the thalamus or neocortex. This shift is first detected inside the basal ganglia, a structure on the path of thalamic axons, and which develops abnormally in Ebf1(-/-) embryos. A similar shift in the topography of thalamocortical axons inside the basal ganglia and neocortex was observed in Dlx1/2(-/-) embryos, which also have an abnormal basal ganglia development. Furthermore, Dlx1 and Dlx2 are not expressed in the dorsal thalamus or in cortical projections neurons. Thus, our study shows that: (1) different thalamic nuclei do not establish projections independently of each other; (2) a shift in thalamocortical topography can occur in the absence of major regionalization defects in the dorsal thalamus and neocortex; and (3) the basal ganglia may contain decision points for thalamic axons' pathfinding and topographic organization. These observations suggest that the topography of thalamocortical projections is not strictly determined by cues located within the neocortex and may be regulated by the relative positioning of thalamic axons inside the basal ganglia.     

Active neocortical processes during quiescent sleep

The neocortex and the thalamus constitute a unified oscillatory machine during different states of vigilance. The cortically generated slow sleep oscillation has the virtue of grouping other sleep rhythms, including those arising in the thalamus, within complex wave-sequences. Despite the coherent oscillatory activity in corticothalamic circuits, on the functional side there is dissociation between thalamus and neocortex during sleep. While dorsal thalamic neurons undergo inhibitory processes induced by prolonged spikebursts of GABAergic thalamic reticular neurons, the cortex displays, periodically, a rich spontaneous activity and preserves the capacity to process internally generated signals. Simultaneous intracellular recordings from thalamic and cortical neurons show that short-term plasticity processes occur after prolonged and rhythmic spike-bursts fired by thalamic and cortical neurons during slow-wave sleep oscillations. This may serve to support resonant phenomena and reorganize corticothalamic circuitry.     

Neuronal Gap Junctions in Cortical Columns and Nuclei of the Ventral Thalamus of Rats

Functional cortical columns and nuclei of the ventral thalamus play a key role in processing of sensory information; therefore, detailed studies on formation of neuron-to-neuron gap junctions in these areas are of great theoretical and practical importance. In the present study, we applied electron-microscopy methods to examine the structure and specific distribution of interneuronal gap junctions in the cortical layer IV and thalamic nuclei, including VPM, RTN, Pom, and VPL. In the cortex, we found more interneuronal gap junctions than in thalamic nuclei. In all structures studied we revealed and described axo-dendritic, dendrodendritic, and “mixed” synapses. We report on the axo-dendritic gap junctions for the first time. It is suggested that this type of contacts plays some functional role in local synchronization of neuronal activity within one ensemble on the presynaptic level.     

Thalamic circuitry and thalamocortical synchrony

The corticothalamic system has an important role in synchronizing the activities of thalamic and cortical neurons. Numerically, its synapses dominate the inputs to relay cells and to the gamma-amino butyric acid (GABA)ergic cells of the reticular nucleus (RTN). The capacity of relay neurons to operate in different voltage-dependent functional modes determines that the inputs from the cortex have the capacity directly to excite the relay cells, or indirectly to inhibit them via the RTN, serving to synchronize high- or low-frequency oscillatory activity respectively in the thalamocorticothalamic network. Differences in the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subunit composition of receptors at synapses formed by branches of the same corticothalamic axon in the RTN and dorsal thalamus are an important element in the capacity of the cortex to synchronize low-frequency oscillations in the network. Interactions of focused corticothalamic axons arising from layer VI cortical cells and diffuse corticothalamic axons arising from layer V cortical cells, with the specifically projecting core relay cells and diffusely projecting matrix cells of the dorsal thalamus, form a substrate for synchronization of widespread populations of cortical and thalamic cells during high-frequency oscillations that underlie discrete conscious events.     

The Role of Thalamic Population Synchrony in the Emergence of Cortical Feature Selectivity

In a wide range of studies, the emergence of orientation selectivity in primary visual cortex has been attributed to a complex interaction between feed-forward thalamic input and inhibitory mechanisms at the level of cortex. Although it is well known that layer 4 cortical neurons are highly sensitive to the timing of thalamic inputs, the role of the stimulus-driven timing of thalamic inputs in cortical orientation selectivity is not well understood. Here we show that the synchronization of thalamic firing contributes directly to the orientation tuned responses of primary visual cortex in a way that optimizes the stimulus information per cortical spike. From the recorded responses of geniculate X-cells in the anesthetized cat, we synthesized thalamic sub-populations that would likely serve as the synaptic input to a common layer 4 cortical neuron based on anatomical constraints. We used this synchronized input as the driving input to an integrate-and-fire model of cortical responses and demonstrated that the tuning properties match closely to those measured in primary visual cortex. By modulating the overall level of synchronization at the preferred orientation, we show that efficiency of information transmission in the cortex is maximized for levels of synchronization which match those reported in thalamic recordings in response to naturalistic stimuli, a property which is relatively invariant to the orientation tuning width. These findings indicate evidence for a more prominent role of the feed-forward thalamic input in cortical feature selectivity based on thalamic synchronization.     

Unit responses of the medial group of thalamic nuclei to stimulation of the frontobasal regions of the neocortex

In acute experiments on cats anesthetized with pentobarbital and chloralose, single-unit and focal responses of the medial group of thalamic nuclei (mediodorsal, central lateral, paracentral, central medianum, parafascicular) were studied to stimulation of the frontobasal regions of the cortex (proreal, posterior orbital, basal temporal regions). Depending on the number of neurons responding to cortical stimulation and on the length of the latent period of the responses three functionally heterogeneous subdividions of the medial nuclei were distinguished; the parvocellular and magnocellular portions of the mediodorsal nucleus and the intralaminar nuclei with the parafascicular complex. On the basis of responses of neurons activated antidromically by stimulation of the same cortical region and synaptically by stimulation of another region, the concept of the integrative function of nuclei of the medial group, integrating the frontobasal zones of the neocortex with the aid of neuron circuits in which the medial nuclei are included, is argued.M. Gor'kii Donetsk Medical Institute. Translated from Neirofiziologiya, Vol. 9, No. 1, pp. 11–18, January–February, 1977.     

Kainic acid—induced excitotoxicity is associated with a complex c-Fos and c-Jun response which does not preclude either cell death or survival

c-fos and c-jun mRNA induction and c-Fos and c-Jun protein expression were examined in the brains of adult rats subjected to systemic kainic acid (KA) injection at convulsant doses. Induction of c-fos and c-jun mRNA, as seen with in situ hybridization, occurred in the piriform and entorhinal cortices, neocortex, amygdala, hippocampus, dentate gyrus, and discrete thalamic nuclei. This was followed by c-Fos protein expression, as revealed with immunohistochemistry, in the same regions. However, the distribution of c-Jun protein expression differed depending on the antibody used. The distribution of cells immunostained with the antibody c-Jun (AB-1) was similar to that of c-jun mRNA, but the distribution of cells immunostained with the antibody c-Jun/AP1 (N) was restricted to a few neurons in the pyramidal cell layer of CA1 and CA3, layer II of the piriform and entorhinal cortices, basal amygdala, and discrete thalamic nuclei. Although the regional distribution of c-Fos- and c-Jun-immunoreactive cells in the hippocampus, layer II of the entorhinal and piriform cortices, basal amygdala, and discrete thalamic nuclei matched the distribution of cells committed to dying, c-Fos- and c-Jun-immunoreactive cells in the neocortex and dentate gyrus survived. Therefore, the present data show that c-fos and c-jun are not predictors of either cell death or survival, but rather, markers of cells sensitive to KA excitotoxicity. Western blots to c-Fos showed a double band at p62 in samples containing the hippocampus and entorhinal and piriform cortices (hip samples) and in samples containing the neocortex (cortex samples). The upper band was abolished following preincubation of the samples with alkaline phosphatase, thus suggesting c-Fos phosphorylation. Western blots to c-Jun (AB-1) showed a single band at about p39 in hip and cortex. However, Western blots to c-Jun/AP1 (N) identified two bands. One band at about p39 was seen in control rats and the cortex of KA-treated rats. Another band at p26 was observed only in hip samples of KA-treated rats. In addition, decreased c-Jun N-terminal kinase 1 (JNK-1) expression, as revealed on Western blots, was coincidental with the appearance of the p26 c-Jun-immunoreactive band in KA-treated rats. These results show that c-Fos and different Jun-related antigens are expressed following KA excitotoxicity, and that posttranslational modifications involving phosphorylation of c-Fos and Jun(s) may occur following KA injection. These results also stress the necessity of examining the composition of Fos and Jun-related antigens and the metabolic state of Fos and Jun(s) in different experimental models of nervous system injury. © 1997 John Wiley & Sons, Inc. J Neurobiol 33: 232–246, 1997     

Central Projection of Pain Arising from Delayed Onset Muscle Soreness (DOMS) in Human Subjects

Delayed onset muscle soreness (DOMS) is a subacute pain state arising 24–48 hours after a bout of unaccustomed eccentric muscle contractions. Functional magnetic resonance imaging (fMRI) was used to examine the patterns of cortical activation arising during DOMS-related pain in the quadriceps muscle of healthy volunteers evoked by either voluntary contraction or physical stimulation. The painful movement or physical stimulation of the DOMS-affected thigh disclosed widespread activation in the primary somatosensory and motor (S1, M1) cortices, stretching far beyond the corresponding areas somatotopically related to contraction or physical stimulation of the thigh; activation also included a large area within the cingulate cortex encompassing posteroanterior regions and the cingulate motor area. Pain-related activations were also found in premotor (M2) areas, bilateral in the insular cortex and the thalamic nuclei. In contrast, movement of a DOMS-affected limb led also to activation in the ipsilateral anterior cerebellum, while DOMS-related pain evoked by physical stimulation devoid of limb movement did not.     

Ephrins regulate the formation of terminal axonal arbors during the development of thalamocortical projections

The development of connections between thalamic afferents and their cortical target cells occurs in a highly precise manner. Thalamic axons enter the cortex through deep cortical layers, then stop their growth in layer 4 and elaborate terminal arbors specifically within this layer. The mechanisms that underlie target layer recognition for thalamocortical projections are not known. We compared the growth pattern of thalamic explants cultured on membrane substrates purified from cortical layer 4, the main recipient layer for thalamic axons, and cortical layer 5, a non-target layer. Thalamic axons exhibited a reduced growth rate and an increased branching density on their appropriate target membranes compared with non-target substrate. When confronted with alternating stripes of both membrane substrates, thalamic axons grew preferentially on their target membrane stripes. Enzymatic treatment of cortical membranes revealed that growth, branching and guidance of thalamic axons are independently regulated by attractive and repulsive cues differentially expressed in distinct cortical layers. These results indicate that multiple membrane-associated molecules collectively contribute to the laminar targeting of thalamic afferents. Furthermore, we found that interfering with the function of Eph tyrosine kinase receptors and their ligands, ephrins, abolished the preferential branching of thalamic axons on their target membranes, and that recombinant ephrin-A5 ligand elicited a branch-promoting activity on thalamic axons. We conclude that interactions between Eph receptors and ephrins mediate branch formation of thalamic axons and thereby may play a role in the establishment of layer-specific thalamocortical connections.