The distribution of corticocortical, thalamocortical, and callosal inputs on identified motor cortex output neurons: mechanisms for their selective recruitment.

Motor cortex neurons were identified antidromically in anesthetized cats by their axonal projections to one of six targets: (1) somatosensory cortex, (2) opposite motor cortex, (3) red nucleus, (4) lateral reticular nucleus, (5) spinal cord, and (6) ventrolateral thalamus. Three inputs to motor cortex were tested for their influences on the identified cortical efferent neurons. The tested inputs originated from ipsilateral somatosensory cortex, opposite motor cortex, and ventral thalamus. Subthreshold effects of input pathways were detected by monitoring latency variations of antidromic responses. The three afferent sources, when activated by electrical stimulation, were not equally effective on motor cortex neurons. Ipsilateral corticocortical and thalamocortical excitation were found for the majority of neurons; the influenced proportions ranged from 55% to 100%, according to the target of the output neurons. Effects from the opposite hemisphere were found for only 5% to 30% of the neurons in the same projection classes. Many neurons (36 of 81, or 44%) were excited from more than one source, but few (5 of 37, or 14%) were influenced by all three possible sources of input, even in small regions of cortex innervated by all three of the inputs. Among 19 electrode tracks where all three inputs were present, there were only 2 tracks where all the neurons shared the same combination of inputs. Even for neurons in closest anatomical proximity ("clusters"), it was unusual (only 7 of 25 clusters) for all the neurons to have the same input pattern. Among the seven clusters where all the neurons shared the same input pattern, five of the clusters projected to the same target. These variable combinations of inputs to motor cortex neurons support the conclusion that efferent neurons could be recruited selectively from separate cortical layers or from within clusters of nearby neurons, according to the target of their axonal projection.     

Role of the caudate nucleus in the development of evoked synchronized activity

Synchronized activity (spindles, augmentation response) evoked by stimulation of thalamic nonspecific, association, and specific nuclei was investigated in chronic experiments on 11 cats before and after successive destruction of the caudate nuclei. After destruction of the caudate nuclei the duration of spindle activity in the frontal cortex and subcortical formations (thalamic nuclei, globus pallidus, putamen) was reduced to only three or four oscillations. In the subcortical nuclei its amplitude fell significantly (by 50±10%); in the cortex the decrease in amplitude was smaller and in some cases was not significant. Different changes were observed in the amplitude of the augmentation response, depending on where it was recorded. In the subcortical formations it was considerably and persistently reduced (by 50±10%); in the cortex these changes were unstable in character. Unilateral destruction of the caudate nucleus inhibited synchronized activity evoked by stimulation of the thalamic nuclei on the side of the operation only. Destruction of the basal ganglia (caudate nucleus, globus pallidus, entopeduncular nucleus, and putamen) did not prevent the appearance of synchronized activity; just as after isolated destruction of the caudate nucleus, after this operation synchronized activity was simply reduced in duration and amplitude. It is suggested that the caudate nucleus exerts an ipsilateral facilitatory influence on the nonspecific system of the thalamus during the development of evoked synchronized activity.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 9, No. 3, pp. 239–248, May–June, 1977.     

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.     

Functional architecture of auditory cortex

Three complementary approaches demonstrate new types of organization in rodent, feline and primate auditory cortex, as well as differences in processing between auditory and visual cortex. First, connectional work reveals patterns of thalamocortical and corticocortical input unique to the auditory cortex. Second, physiological studies find multiple, interleaved auditory processing modules related to corticocortical connections and embedded in the isofrequency gradient. Third, functional analyses demonstrate independent processing streams for sound localization and identification analogous to the 'what' and 'where' streams in visual cortex, although the modular arrangements are modality-specific. Taken together, these data show that the auditory cortex has common and unique functional substrates.     

Independent parcellation of the embryonic visual cortex and thalamus revealed by combinatorial Eph/ephrin gene expression

The visual cortex in primates is parcellated into cytoarchitectonically, physiologically, and connectionally distinct areas: the striate cortex (V1) and the extrastriate cortex, consisting of V2 and numerous higher association areas [1]. The innervation of distinct visual cortical areas by the thalamus is especially segregated in primates, such that the lateral geniculate (LG) nucleus specifically innervates striate cortex, whereas pulvinar projections are confined to extrastriate cortex [2--8]. The molecular bases for the parcellation of the visual cortex and thalamus, as well as the establishment of reciprocal connections between distinct compartments within these two structures, are largely unknown. Here, we show that prospective visual cortical areas and corresponding thalamic nuclei in the embryonic rhesus monkey (Macaca mulatta) can be defined by combinatorial expression of genes encoding Eph receptor tyrosine kinases and their ligands, the ephrins, prior to obvious cytoarchitectonic differentiation within the cortical plate and before the establishment of reciprocal connections between the cortical plate and thalamus. These results indicate that molecular patterns of presumptive visual compartments in both the cortex and thalamus can form independently of one another and suggest a role for EphA family members in both compartment formation and axon guidance within the visual thalamocortical system.     

The Distribution of Corticocortical,Thalamocortical, and Callosal Inputs on Identified Motor Cortex Output Neurons: Mechanisms for Their Selective Recruitment

Motor cortex neurons were identified antidromically in anesthetized cats by their axonal projections to one of six targets: (1) somatosensory cortex, (2) opposite motor cortex, (3) red nucleus, (4) lateral reticular nucleus, (5) spinal cord, and (6) ventrolateral thalamus. Three inputs to motor cortex were tested for their influences on the identified cortical efferent neurons. The tested inputs originated from ipsilateral somatosensory cortex, opposite motor cortex, and ventral thalamus. Subthreshold effects of input pathways were detected by monitoring latency variations of antidromic responses.

The three afferent sources, when activated by electrical stimulation, were not equally effective on motor cortex neurons. Ipsilateral corticocortical and thalamocortical excitation were found for the majority of neurons; the influenced proportions ranged from 55% to 100%, according to the target of the output neurons. Effects from the opposite hemisphere were found for only 5% to 30% of the neurons in the same projection classes.

Many neurons (36 of 81, or 44%) were excited from more than one source, but few (5 of 37, or 14%) were influenced by all three possible sources of input, even in small regions of cortex innervated by all three of the inputs. Among 19 electrode tracks where all three inputs were present, there were only 2 tracks where all the neurons shared the same combination of inputs. Even for neurons in closest anatomical proximity (“clusters”), it was unusual (only 7 of 25 clusters) for all the neurons to have the same input pattern. Among the seven clusters where all the neurons shared the same input pattern, five of the clusters projected to the same target. These variable combinations of inputs to motor cortex neurons support the conclusion that efferent neurons could be recruited selectively from separate cortical layers or from within clusters of nearby neurons, according to the target of their axonal projection.     

On variability in the density of corticocortical and thalamocortical connections

Variability is an important but neglected aspect of connectional neuroanatomy. The quantitative density of the 'same' corticocortical or thalamocortical connection may vary by over two orders of magnitude between different injections of the same tracer. At present, however, the frequency distribution of connection densities is unknown. Therefore, it is unclear what kind of sampling strategies or statistical methods are appropriate for quantitative studies of connectivity. Nor is it clear if the measured variability represents differences between subjects, or if it is simply a consequence of intra-individual differences resulting from experimental technique and the exact placement of tracers relative to local spatial and laminar variation in connectivity. We used quantitative measurements of the density of a large number of corticocortical and thalamocortical connections from our own laboratories and from the literature. Variability in the density of given corticocortical and thalamocortical connections is high, with the standard deviation of density proportional to the mean. The frequency distribution is close to exponential. Therefore, analysis methods relying on the normal distribution are not appropriate. We provide an appendix that gives simple statistical guidance for samples drawn from exponentially distributed data. For a given corticocortical or thalamocortical connection density, between-individual standard deviation is 0.85 to 1.25 times the within-individual standard deviation. Therefore, much of the variability reported in conventional neuroanatomical studies (with one tracer deposited per animal) is due to within-individual factors. We also find that strong, but not weak, corticocortical connections are substantially more variable than thalamocortical connections. We propose that the near exponential distribution of connection densities is a simple consequence of 'patchy' connectivity. We anticipate that connection data will be well described by the negative binomial, a class of distribution that applies to events occurring in clumped or patchy substrates. Local patchiness may be a feature of all corticocortical connections and could explain why strong corticocortical connections are more variable than strong thalamocortical connections. This idea is supported by the columnar patterns of many corticocortical but few thalamocortical connections in the literature.     

Comparison of fMRI BOLD Response Patterns by Electrical Stimulation of the Ventroposterior Complex and Medial Thalamus of the Rat

The objective of this study was to compare the functional connectivity of the lateral and medial thalamocortical pain pathways by investigating the blood oxygen level-dependent (BOLD) activation patterns in the forebrain elicited by direct electrical stimulation of the ventroposterior (VP) and medial (MT) thalamus. An MRI-compatible stimulation electrode was implanted in the VP or MT of α-chloralose-anesthetized rats. Electrical stimulation was applied to the VP or MT at various intensities (50 µA to 300 µA) and frequencies (1 Hz to 12 Hz). BOLD responses were analyzed in the ipsilateral forelimb region of the primary somatosensory cortex (iS1FL) after VP stimulation and in the ipsilateral cingulate cortex (iCC) after MT stimulation. When stimulating the VP, the strongest activation occurred at 3 Hz. The stimulation intensity threshold was 50 µA and the response rapidly peaked at 100 µA. When stimulating the MT, The optimal frequency for stimulation was 9 Hz or 12 Hz, the stimulation intensity threshold was 100 µA and we observed a graded increase in the BOLD response following the application of higher intensity stimuli. We also evaluated c-Fos expression following the application of a 200-µA stimulus. Ventroposterior thalamic stimulation elicited c-Fos-positivity in few cells in the iS1FL and caudate putamen (iCPu). Medial thalamic stimulation, however, produced numerous c-Fos-positive cells in the iCC and iCPu. The differential BOLD responses and c-Fos expressions elicited by VP and MT stimulation indicate differences in stimulus-response properties of the medial and lateral thalamic pain pathways.     

Laminar specificity of extrinsic cortical connections studied in coculture preparations.

The formation of specific neural connections in the cerebral cortex was studied using organotypic coculture preparations composed of subcortical and cortical regions. Morphological and electrophysiological analysis indicated that several cortical efferent and afferent connections, such as the corticothalamic, thalamocortical, corticocortical, and corticotectal connections, were established in the cocultures with essentially the same laminar specificity as that found in the adult cerebral cortex, but without specificity of sensory modality. This suggests the existence of a cell-cell recognition system between cortical or subcortical neurons and their final targets. This interaction produces lamina-specific connections, but is probably insufficient for the formation of the modality-specific connections.     

Correction of changes induced by toluene in the cortical and subcortical structures of albino rat brain

The number and weight of cells in the cortical and subcortical structures of the cerebral and cerebellar motor system in albino rats after a long-term exposure to toluene were determined. Toluene intoxication proved to kill projection neurons and interneurons in the sensorimotor cortex, ventrolateral thalamic nucleus, caudate nucleus, pallidum, red nucleus, and inferior olivary complex. The decreased number of cerebellar cells was mediated by atrophic changes as indicated by the decrease in the area and dry weight of Purkinje cells. The addition of plaferon LB to the diet attenuated the cytotoxic effect of toluene.     

Dentate control pathways of cortical motor activity. Anatomical and physiological studies in rat: comparative considerations

The dentato-thalamocortical projections have been studied in albino rats using anatomical and physiological approaches. The anatomical analysis reveals that the dentatothalamic input to the ventral thalamus and the thalamocortical projection from this region onto the motor cortical area have a complex topographical arrangement. The corticothalamic reverberating pathways, both direct and through a relay in the nucleus reticularis thalami, are also roughly arranged in register with the same topographical pattern. This arrangement has been reconciled with that of the motor cortex, as determined by the motor effects of intracortical microstimulations. From this is inferred a somatotopical arrangement of the cerebellar nucleus lateralis, or dentate. These observations are confirmed by the results of our physiological analysis. The movements obtained with direct microstimulations of the nucleus lateralis affect either one joint (simple movements) or, more seldom, several joints (complex movements) of the same limb. A rough rostrocaudal arrangement is found in the nucleus lateralis: the caudocentral regions of the nucleus contain the representation of the musculature of forelimb and head, whereas the hindlimb is represented in the rostralmost part of the nucleus. A more complex organization is found to be related to the three cytoarchitectonic subdivisions of the nucleus lateralis. The main, large-celled part of the nucleus is engaged in the control of the large skeletal musculature. The dorsolateral hump is involved in mouth and peri-oral activities. The ventral, parvocellular, subnucleus is involved in fine exploratory movements of vibrissae, eyes, and forelimb wrist and fingers. The implication of the dentato-thalamocortical pathways in the cortical motor activities in the rat is discussed with attention to the dentate control of the "voluntary" motricity in primates.     

Striatal input from the ventrobasal complex of the rat thalamus

We have analyzed whether caudal regions of the caudate putamen receive direct projections from thalamic sensory relay nuclei such as the ventrobasal complex. To this aim, the delivery of the retrograde neuroanatomical tracer Fluoro-Gold into the caudal caudate putamen resulted in the appearance of retrogradely labeled neurons in the ventral posteromedial and ventral posterolateral thalamic nuclei. These projections were further confirmed with injections of the anterograde tracers biotinylated dextran amine or Phaseolus vulgaris leucoagglutinin into these thalamic nuclei, by showing the existence of axonal terminal fields located in the caudal striatum. These results support the existence of direct projections linking the thalamic ventrobasal complex and the caudal striatum in the rat, probably via collateralization of thalamocortical axons when passing through the caudate putamen, and therefore supporting the putative involvement of the caudal striatum in sensory-related functions.     

Arrangement and connections of mesencephalic trigeminal neurons in the rat

The morphology of the mesencephalic trigeminal nucleus was examined microscopically in serial frozen sections. The nucleus extends over a length of about 4.5 mm, and its cell number was calculated to range from 1,000 to 1,600. 60% of the cells were located in the caudal third of the nucleus. Clustering of large unipolar cells was seen throughout the nucleus. Small spindle-shaped multipolar cells were found in the pontine part of the nucleus. The efferent connections of the mesencephalic trigeminal neurons were investigated by means of iontophoretically delivered Phaseolus vulgaris leuco-agglutinin or horseradish peroxidase after electrophysiological identification of mesencephalic trigeminal neurons. All projections were found ipsilateral to the injection site; they were confined to the trigeminal motor nucleus, especially to its lateral part, and to the dorsolateral reticular formation. The latter projection area included the supratrigeminal nucleus, the nucleus of Probst, and the parvocellular reticular zone. There were no direct projections to the facial or hypoglossal motor nuclei. It is concluded that proprioceptive input from one side is mediated polysynaptically to the bilateral oral final common-path neurons, with the exception of the ipsilateral trigeminal motoneurons.     

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.     

Effect of fenamin and haloperidol on conditioned activity of neurons of the motor cortex and striopallidal system

The activity of neurones in the motor cortex, caudate nucleus, putamen and globus pallidus was studied during elaboration of motor conditioned reflexes to time in rabbits, treated with 1-amphetamine and haloperidol. Mechanisms of reproduction of cells trace activity in the reflex to time at the omission of trials, reacted to 1-amphetamine by increasing the intensity of reactions in the motor cortex and inactivation in putamen cells. The curve of dynamics of intensity changes of trace discharges in the course of a series of trials omissions remained unaltered only in motor cortex; in the other structures it significantly differed from the norm of intact animals. Haloperidol depressed the mechanisms of reproduction of trace reactions of the globus pallidus cells, and made them almost fully inactive in the motor cortex; the putamen neurones reacted to haloperidol by an increase of trace reactions intensity. Against the background of the animal chronic 1-amphetamine intoxication, haloperidol normalized the dynamics and intensity of trace activity. "Therapeutic" effect of haloperidol was most distinctly expressed in the motor cortex and putamen cells, less--in the caudate nucleus and was completely absent in the globus pallidus.     

Electrophysiological characteristics of caudate-thalamic connections

Functional connections between different parts of the caudate nucleus and particular thalamic nucleic were investigated during the onset and development of the recruiting response in chronic experiments on cats. The method of condioning and testing stimulation of subcortical structures was used. The highest degree of functional connection was observed between the caudate nucleus and ventral anterior thalamic nucleus in the ipsilateral hemisphere. It is suggested that caudatethalamic functional connections in the development of synchronized activity are due to the activity of two mechanisms: general and facultative thalamic pacemakers.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 9, No. 6, pp. 570–574, November–December, 1977.     

Nonoverlapping Thalamocortical Connections to Normal and Deprived Primary Somatosensory Cortex for Similar Forelimb Receptive Fields in Chronic Spinal Cats

The fluorescent dye retrograde tracing technique, using fast blue in combination with fluorogold, was used to examine thalamocortical projections from the ventrobasal complex to primary somatosensory cortex in chronic spinal cats that sustained T12 cord transection at 2 weeks of age. Following cord transection at this age, it has been shown that forelimb afferents can excite the deprived hindlimb projection zone, in addition to the region of somatosensory cortex that they normally occupy (McKinley et al, 1987). These two regions of cortex are separated by over 10 mm, thus facilitating the determination of whether the forelimb representation in “hindlimb cortex” is derived from the sector of the ventrobasal complex of the thalamus representing the forelimb, hindlimb, or both. Injections of the two dyes into separate regions of the cortex that were excited by the same peripheral forelimb receptive fields produced single labeling of two nonoverlapping clusters of thalamic neurons. This finding suggests that the projections for these two areas are independent and distinct, and indicates that altered thalamocortical projections do not contribute the critical component underlying reorganizational changes observed at the cortical level after spinal cord transection. It is hypothesized that the degree of reorganization required to achieve the magnitude of change observed in the cortex must occur below the level of the thalamocortical relay.     

Efferent connections of the cat caudate nucleus studied by retrograde axonal transport of horseradish peroxidase

A well-developed descending efferent system of the caudate nucleus has been revealed by retrograde axonal transport of horseradish peroxidase. It consists of numerous projections into the thalamus. A topical differentiation of the connections between the caudate nucleus and the paleostriatum and substantia nigra was found. It was established that the main source of efferent connections of the caudate nucleus were small and medium-sized neurons. It was demonstrated that the subthalamic nucleus has a special role in the descending efferent system of the caudate nucleus. In addition to the direct connections into the caudate nucleus itself the subthalamic nucleus has direct connections with the main output structures of the caudate nucleus, the paleostriatum, and the substantia nigra. The concept that the descending and ascending connections are interlinked in the mammalian central nervous system is supported by the results of this investigation into the caudate nucleus.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 17, No. 4, pp. 509–517, July–August, 1985.     

Neurons of the thalamic ventrobasal complex,labeled with horseradish peroxidase,projecting to the primary somatosensory cortex in cats

The morphology and localization of neurons of the thalamic ventrobasal complex projecting to the primary somatosensory cortex were studied in cats by the retrograde axonal transport of exogenous horseradish peroxidase method. Different types of neurons were detected: triangular, round with symmetrical processes, oval with processes diverging asymmetrically, and fusiform. Tagged neurons were distributed as two large populations in the central region of the complex adjoining the boundaries of the two nuclei. Comparison with the somatotopic map showed that the tagged neurons were concentrated mainly in the projection area of the forelimb and head. Since microinjections of peroxidase into the somatosensory cortex also were given in the projection areas for the forelimb and head, the results confirm the neurophysiological concept of strict somatotopic organization of thalamocortical input.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. A. A. Ukhtomskii Physiological Institute, Leningrad. Translated from Neirofiziologiya, Vol. 11, No. 2, pp. 125–129, March–April, 1979.     

A functional and structural investigation of the human fronto-basal volitional saccade network

Almost all cortical areas are connected to the subcortical basal ganglia (BG) through parallel recurrent inhibitory and excitatory loops, exerting volitional control over automatic behavior. As this model is largely based on non-human primate research, we used high resolution functional MRI and diffusion tensor imaging (DTI) to investigate the functional and structural organization of the human (pre)frontal cortico-basal network controlling eye movements. Participants performed saccades in darkness, pro- and antisaccades and observed stimuli during fixation. We observed several bilateral functional subdivisions along the precentral sulcus around the human frontal eye fields (FEF): a medial and lateral zone activating for saccades in darkness, a more fronto-medial zone preferentially active for ipsilateral antisaccades, and a large anterior strip along the precentral sulcus activating for visual stimulus presentation during fixation. The supplementary eye fields (SEF) were identified along the medial wall containing all aforementioned functions. In the striatum, the BG area receiving almost all cortical input, all saccade related activation was observed in the putamen, previously considered a skeletomotor striatal subdivision. Activation elicited by the cue instructing pro or antisaccade trials was clearest in the medial FEF and right putamen. DTI fiber tracking revealed that the subdivisions of the human FEF complex are mainly connected to the putamen, in agreement with the fMRI findings. The present findings demonstrate that the human FEF has functional subdivisions somewhat comparable to non-human primates. However, the connections to and activation in the human striatum preferentially involve the putamen, not the caudate nucleus as is reported for monkeys. This could imply that fronto-striatal projections for the oculomotor system are fundamentally different between humans and monkeys. Alternatively, there could be a bias in published reports of monkey studies favoring the caudate nucleus over the putamen in the search for oculomotor functions.