Functional imaging of the intraparietal cortex during saccades to visual and memorized targets.

The representation of perceived space and intended actions in the primate parietal cortex has been the subject of considerable debate. To address this issue, we used the quantitative 14C-deoxyglucose method to obtain maps of the activity pattern in the intraparietal cortex of rhesus monkeys executing saccades to visual and memorized targets. The principal effect induced by memory-guided saccades was found more caudally in the deepest part of the middle third of the lateral bank (within area LIPv) whereas that induced by visually guided saccades extended more rostrally and superficially in the anterior third of the bank (within area LIPd). The memory-saccade-related and the visual-saccade-related regions of activation overlapped only within area LIPv. Besides saccade execution, maximal activity in area LIPd required a visual stimulus. The region activated by visual fixation was located at the border of LIPv and LIPd, extending mainly within area LIPd, and occupying about one third of the neural space of the region activated for visual-saccades. We suggest that the lateral intraparietal cortex represents visual and motor space in segregated, albeit partially overlapping, regions.

Frontal cortical areas of the monkey brain engaged in reaching behavior: a (14)C-deoxyglucose imaging study.

The ((14)C)-deoxyglucose method was employed to study whether different areas of the primate frontal lobe are involved in different aspects of reaching behavior. To this end, we mapped the functional activity of the frontal motor cortical areas in three monkeys performing reaching movements with one forelimb. The first monkey had to capture a peripheral visual target with a saccade and a forelimb-reach together, the second monkey had to reach a peripheral visual target with one forelimb while fixating a central target, and the third one had to reach a peripheral memorized target with one forelimb in complete darkness while the eyes maintained a straight ahead direction. The extent and intensity of activations were compared to those of three respective control monkeys: a saccade-control, a fixation-control, and a dark-control. The primary somatosensory (S1) and motor (F1) forelimb representation, the S1- and F1-trunk representation, the F2-dimple region, areas F3-forelimb, F4, F5-bank of arcuate sulcus, F7-ridge, the dorsal bank of cingulate sulcus, and 24 c were activated in all reaching monkeys regardless of accompanying visual stimulation and oculomotor behavior. Interestingly, the S1-forelimb activation in the monkey reaching to memorized targets in complete darkness was more pronounced than that in the monkeys reaching to visual targets in the light, indicating that increased somatosensory processing compensates for the absence of visual feedback. On the other hand, areas F2-periarcuate, F5-convexity, F6, and 23 were preferentially activated by reaching to visual targets and remained unaffected during reaching to memorized targets when no visual feedback was available.

Oculomotor areas of the primate frontal lobes: a transneuronal transfer of rabies virus and [14C]-2-deoxyglucose functional imaging study.

We used the [14C]-2-deoxyglucose method to study the location and extent of primate frontal lobe areas activated for saccades and fixation and the retrograde transneuronal transfer of rabies virus to determine whether these regions are oligosynaptically connected with extraocular motoneurons. Fixation-related increases of local cerebral glucose utilization (LCGU) values were found around the fundus of the inferior limb of the arcuate sulcus (AS) just ventral to its genu, in the dorsomedial frontal cortex (DMFC), cingulate cortex, and orbitofrontal cortex. Significant increases of LCGU values were found in and around both banks of the AS, DMFC, and caudal principal, cingulate, and orbitofrontal cortices of monkeys executing visually guided saccades. All of these areas are oligosynaptically connected to extraocular motoneurons, as shown by the presence of retrogradely transneuronally labeled cells after injection of rabies virus in the lateral rectus muscle. Our data demonstrate that the arcuate oculomotor cortex occupies a region considerably larger than the classic, electrical stimulation-defined, frontal eye field. Besides a large part of the anterior bank of the AS, it includes the caudal prearcuate convexity and part of the premotor cortex in the posterior bank of the AS. They also demonstrate that the oculomotor DMFC occupies a small area straddling the ridge of the brain medial to the superior ramus of the AS. Our results support the notion that a network of several interconnected frontal lobe regions is activated during rapid, visually guided eye movements and that their output is conveyed in parallel to subcortical structures projecting to extraocular motoneurons.

Functional imaging of the primate superior colliculus during saccades to visual targets.

The primate superior colliculus (SC) is a midbrain nucleus crucial for the control of rapid eye movements (saccades). Its neurons are topographically arranged over the rostrocaudal and mediolateral extent of its deeper layers so that saccade metrics (amplitude and direction) are coded in terms of the location of active neurons. We used the quantitative [14C]-deoxyglucose method to obtain a map of the two-dimensional pattern of activity throughout the SC of rhesus monkeys repeatedly executing visually guided saccades of the same amplitude and direction for the duration of the experiment. Increased metabolic activity was confined to a circumscribed region of the two-dimensional reconstructed map of the SC contralateral to the direction of the movement. The precise rostrocaudal and mediolateral location of the area activated depended on saccade metrics. Our data support the notion that the population of active SC cells remains stationary in collicular space during saccades.

The intraparietal cortex: subregions involved in fixation, saccades, and in the visual and somatosensory guidance of reaching.

The functional activity of the intraparietal cortex was mapped with the [14C]deoxyglucose method in monkeys performing fixation of a central visual target, saccades to visual targets, reaching in the light during fixation of a central visual target, and acoustically triggered reaching in the dark while the eyes maintained a straight ahead direction. Different subregions of the intraparietal cortical area 7 were activated by fixation, saccades to visual targets, and acoustically triggered reaching in the dark. Subregions in the ventral part of the intraparietal cortex (around the fundus of the intraparietal sulcus) were activated only during reaching in the light, in which case visual information was available to guide the moving forelimb. In contrast, subregions in the dorsal part of the intraparietal cortical area 5 were activated during both reaching in the light and the dark, in which cases somatosensory information was the only one available in common. Thus, visual guidance of reaching is associated with the ventral intraparietal cortex, whereas somatosensory guidance, based on proprioceptive information about the current forelimb position, is associated with dorsal intraparietal area 5.

14C-deoxyglucose mapping of the monkey brain during reaching to visual targets.

The strategies used by the macaca monkey brain in controlling the performance of a reaching movement to a visual target have been studied by the quantitative autoradiographic 14C-DG method. Experiments on visually intact monkeys reaching to a visual target indicate that V1 and V2 convey visuomotor information to the cortex of the superior temporal and parietoccipital sulci which may encode the position of the moving forelimb, and to the cortex in the ventral part and lateral bank of the intraparietal sulcus which may encode the location of the visual target. The involvement of the medial bank of the intraparietal sulcus in proprioceptive guidance of movement is also suggested on the basis of the parallel metabolic effects estimated in this region and in the forelimb representations of the primary somatosensory and motor cortices. The network including the inferior postarcuate skeletomotor and prearcuate oculomotor cortical fields and the caudal periprincipal area 46 may participate in sensory-to-motor and oculomotor-to-skeletomotor transformations, in parallel with the medial and lateral intraparietal cortices. Experiments on split brain monkeys reaching to visual targets revealed that reaching is always controlled by the hemisphere contralateral to the moving forelimb whether it is visually intact or 'blind'. Two supplementary mechanisms compensate for the 'blindness' of the hemisphere controlling the moving forelimb. First, the information about the location of the target is derived from head and eye movements and is sent to the 'blind' hemisphere via inferior parietal cortical areas, while the information about the forelimb position is derived from proprioceptive mechanisms and is sent via the somatosensory and superior parietal cortices. Second, the cerebellar hemispheric extensions of vermian lobules V, VI and VIII, ipsilateral to the moving forelimb, combine visual and oculomotor information about the target position, relayed by the 'seeing' cerebral hemisphere, with sensorimotor information concerning cortical intended and peripheral actual movements of the forelimb, and then send this integrated information back to the motor cortex of the 'blind' hemisphere, thus enabling it to guide the contralateral forelimb to the target.

Metabolic activity patterns in the monkey visual cortex as revealed by spectral analysis.

The metabolic activity pattern of the monkey visual cortex was mapped quantitatively with [14C]-2-deoxyglucose during the performance of a visually guided reaching task. After bandpass filtering of the reconstructed two-dimensional metabolic maps of areas V1 and V2, alternating bands of high and low metabolic activity were apparent in control and experimental hemispheres. The spatial arrangement of active bands was studied with two-dimensional spectral analysis, and bands were found to be more organized in the experimental monkey. In area V1 of the control monkey the spectral amplitude was spread over a wider range of directions and frequencies than in the experimental subject. The finding that layer IV is characterized by more complex spectra than layers I through III suggests the coexistence of more than one active columnar system in the geniculorecipient layer. In area V2, stripes running almost perpendicular to the V1/V2 border were found along with superimposed patches of enhanced metabolic activity. In the experimental hemispheres, the corresponding spectra were extremely sharp yielding a constant periodicity. It is suggested that the well-organized columnar arrangement within areas V1 and V2 of the experimental hemispheres emerges from the diffusely organized background network of activity patterns in the control state.

Spatial cortical patterns of metabolic activity in monkeys performing a visually guided reaching task with one forelimb.

The 2-[14C]deoxyglucose method was used to map the metabolic activity in the neocortex of monkeys (Macaca nemestrina) performing a visually guided reaching task with one forelimb. Monkeys received liquid reward for correct, single directional reaching movements, which were required at a rate of about 10 per minute. We estimated the weighted average of local glucose consumption within several neocortical areas, and we reconstructed quantitative, high-resolution, two-dimensional maps of the detailed spatiointensive patterns of activity. Our findings demonstrate the involvement of the striate and prestriate cortices, the inferior intraparietal and superior temporal visual association areas, the frontal eye field and the caudal periprincipal cortex, the primary somatosensory and the related superior intraparietal area, the primary and association auditory cortices, the superior temporal multimodal region, and the premotor, primary, supplementary, and cingulate motor areas. The visual cortex in the superior temporal and the intraparietal sulci, which is concerned with "where", was activated during visually guided reaching. In contrast, the inferior temporal visual association cortex, which is concerned with "what", was not involved in our study. We suggest that the activated direction-selective layer four of V1 and the thick stripes of V2 convey visuomotor information to the activated cortex in the posterior bank and the floor of the superior temporal sulcus, which may encode the constantly updated position of the moving forelimb. In parallel, the activated cortex in the ventral part and the lateral bank of the intraparietal sulcus may encode visuospatial information related to the localization of the visual target in the extrapersonal space. Furthermore, the dorsal part of the medial bank of the intraparietal sulcus may be involved in proprioceptive guidance of movement, based on the parallel metabolic effects shown only contralateral to the moving forelimb within this region and the forelimb representations in the primary somatosensory and motor cortices. Finally, the bilaterally activated network including the inferior postarcuate skeletomotor and prearcuate oculomotor cortical fields and the caudal periprincipal region 46 may participate in sensory and oculomotor to motor transformations, in parallel with the medial and lateral intraparietal cortices with which this network is reciprocally interconnected.

Visually guided reaching with the forelimb contralateral to a "blind" hemisphere in the monkey: contribution of the cerebellum.

Metabolic activity was mapped in the cerebellar cortex and its major inputs and projection targets in monkeys performing visually guided reaching with the left forelimb. Normal monkeys and monkeys deprived of visual input to the right cerebral hemisphere by right optic tract section, combined in some cases with forebrain commissurotomy, were studied. We reported previously that visually guided reaching with the left forelimb activated the motor cortex of the right hemisphere equally in all these monkeys, indicating that reaching was controlled by the right hemisphere whether it was visually intact or "blind" [Savaki H.E. et al. (1993) J. Neurosci. 13, 2772-2789]. In the present study, metabolic activations were observed in the left cerebellar hemispheric extensions of vermian lobules V, VI and VIII, again regardless of whether the right hemisphere was visually intact or "blind". In intact monkeys, however, the activations were significantly smaller in the lateral than in the paravermal zone of these hemispheric extensions, whereas in tractotomized/commissurotomized monkeys the activations were equal in the two zones. The greater activations in the left lateral zone in tractotomized/commissurotomized monkeys may represent compensation in part for the visual deafferentation of the right cerebral hemisphere. Also observed were metabolic activation in the left dorsolateral pontine nucleus in tractotomized/commissurotomized monkeys and metabolic depression in the left dentate nucleus in visually intact monkeys. This pattern of results suggests the following conclusions. The activated loci in the left cerebellar cortex combine (i) visual information about the target relayed by seeing cerebral hemispheres, and (ii) sensorimotor information concerning intended and actual movements of the left forelimb relayed by the right cerebral hemisphere and the limb, respectively, and then (iii) send this integrated information back to the motor cortex of the right cerebral hemisphere, thus enabling it to guide the left forelimb to the target whether the hemisphere is visually intact or "blind".

Metabolic activity pattern in the motor and somatosensory cortex of monkeys performing a visually guided reaching task with one forelimb.

The [14C]deoxyglucose method was used to map the metabolic activity in the primary somatosensory and motor cortex in monkeys (Macaca nemestrina) performing a unimanual task. The task required visually guided reaching and target holding at a rate of about 10 movements per min. The entire dorsoventral extent of the cortical region lying between the posterior crown of the arcuate and the anterior crown of the intraparietal sulci was reconstructed on the sagittal plane, from horizontal sections aligned on the fundus of the central sulcus. The metabolic mapping of the control monkey demonstrated homogeneous activity all around the central sulcus, bilaterally. The mapped activity in the performing monkeys displayed two different patterns. The first pattern, contralateral to the moving forelimb, was characterized by several discrete regions of increased metabolic activity, which were symmetrically distributed in a mirror image fashion around the fundus of the central sulcus. These activated regions correspond to the lower body, forelimb, and mouth areas of representation of body parts in previously reported maps in primary motor and somatosensory cortical areas. The second activity pattern ipsilateral to the moving forelimb, displayed activated somatosensory and motor regions corresponding only to the lower body, and mouth representations. Our study provides a continuous, high resolution map of activity pattern in the entire primary motor and somatosensory cortices, which demonstrates that the reaching forelimb is controlled by a discrete subregion in the contralateral somatosensorimotor cortex, whereas other subregions of body representation are actively involved, bilaterally, during the performance of a relatively simple motor behaviour.

Functional anatomy of the thalamic reticular nucleus as revealed with the [14C]deoxyglucose method following electrical stimulation and electrolytic lesion.

The [14C]-deoxyglucose quantitative autoradiographic method was used to map the metabolic changes induced by electrical stimulation and electrolytic lesion of the rostral pole of the thalamic reticular nucleus in the rat brain. Unilateral electrical stimulation of the thalamic reticular nucleus induced the following changes in glucose utilization: (i) local enhancement of metabolic activity within the stimulated thalamic reticular nucleus, (ii) increase in glucose consumption in the ipsilateral thalamic mediodorsal, centrolateral, ventromedial and ventrolateral nuclei, as well as in the nucleus accumbens, (iii) bilateral depression of metabolism in the locus coeruleus, periaqueductal gray, ventral tegmental area, and medial habenula, as well as contralateral metabolic depression in the substantia nigra reticulata, compacta and in the ventral pallidum. Unilateral electrolytic lesion of thalamic reticular nucleus elicited metabolic depression in the ipsilateral thalamic mediodorsal, centrolateral, ventrolateral and ventromedial nuclei, and metabolic activation in the dorsal tegmental nucleus bilaterally. The existence of a descending thalamic reticular nucleus input to the periaqueductal gray is supported by the depressed activity measured in brain stem structures after thalamic reticular nucleus stimulation. The similar effects observed in the periaqueductal gray and substantia nigra contralateral to the stimulated thalamic reticular nucleus indicate a possible flow of information from one thalamic reticular nucleus to the contralateral basal ganglia via the periaqueductal gray. The opposite effects induced in the dorsal thalamic nuclei by thalamic reticular nucleus stimulation and lesion support the gating role of the thalamic reticular nucleus in the information flow between thalamus and cortex.

Functional anatomy of the thalamic centrolateral nucleus as revealed with the [14C]deoxyglucose method following electrical stimulation and electrolytic lesion.

The effects of electrical stimulation and electrolytic lesion of the thalamic intralaminar centrolateral nucleus were studied in the rat brain by means of the quantitative autoradiographic [14C]deoxyglucose method. Unilateral electrical stimulation of the centrolateral nucleus induced: (i) local increase in metabolic activity within the stimulated centrolateral nucleus and the ipsilateral thalamic mediodorsal nucleus, (ii) metabolic depression in all layers of the ipsilateral frontal cortex, (iii) bilateral increase in glucose consumption within the periaqueductal gray, pedunculopontine nucleus, and pontine reticular formation, and (iv) contralateral metabolic activation in the deep cerebellar nuclei. The unilateral electrolytic lesion of the thalamic centrolateral nucleus elicited metabolic depressions in several distal brain areas. The metabolic depression elicited in the mediodorsal, ventrolateral, and lateral thalamic nuclei, as well as in the caudate nucleus, the cingulate, and the superficial layers of forelimb cortex were ipsilateral to the lesioned side. The metabolic depression measured in the medulla and pons (medullary and pontine reticular formation, periaqueductal gray, locus coeruleus, dorsal tegmental, cuneiformis, raphe and pedunculopontine tegmental nuclei), the cerebellum (molecular and granular layers of the cerebellar cortex, interpositus and dentate nuclei), the mesencephalon (substantia nigra reticulata, ventral tegmental area and deep layers of the superior colliculus), the diencephalon (medial habenula, parafascicular, ventrobasal complex, centromedial and reticular thalamic nuclei), the rhinencephalon (dentate gyrus and septum), the basal ganglia (ventral pallidum, globus pallidus, entopeduncular and accumbens nuclei) and the cerebral cortex (superficial and deep layers of the frontal and parietal cortex, deep layers of the forelimb cortex) were bilateral. These functional effects are discussed in relation to known anatomical pathways. The bilateral effects induced by the centrolateral nucleus lesion reflect an important role of the centrolateral nucleus in the processing of reticular activating input and in the interhemispheric transfer of information. The cortical metabolic depression induced by centrolateral nucleus stimulation indicates the participation of this nucleus in attentional functions.

Functional metabolic mapping of the rat brain during unilateral electrical stimulation of the subthalamic nucleus.

The alterations in local metabolic activity of several anatomically distinct brain areas were investigated by means of the quantitative autoradiographic 2-deoxy-D-[1-14C]glucose method in awake rats during unilateral electrical stimulation of the subthalamic nucleus (STH). Unilateral electrical stimulation of the STH induced local metabolic activation (by 70% as compared with the control group), as well as distal metabolic activations in the substantia nigra reticulata (by 34%), globus pallidus (by 19%), entopeduncular nucleus (by 18%), deep layers of the superior colliculi (by 15%), and parafascicular thalamic nucleus (by 18%), ipsilaterally to the stimulated side. The ventrolateral motor thalamic nucleus as well as the limbic components, posterior cingulate cortex, and anteroventral thalamic nucleus displayed bilateral metabolic activations (by 20-28%). These results indicate that, in addition to its known ipsilateral motor connections, each STH is functionally related to the limbic system bilaterally. It is suggested that the STH is a site where the central motor information is accessible to the limbic system. Quantitative image analysis of individual serial sections in the STH, substantia nigra, and globus pallidus revealed a consistent dorsoventral pattern of topographic interrelations. Stimulation of either the dorsal or the ventral subdivision of the STH induced always stronger activation in the dorsal compartment of the substantia nigra and in the ventral compartment of the globus pallidus. These results suggest that the earlier-described inversion of the dorsoventral functional correspondence between the substantia nigra and globus pallidus may be partly mediated via the subthalamic nerve cells projecting collateral axons to both these areas.

Visually guided reaching with the forelimb contralateral to a "blind" hemisphere: a metabolic mapping study in monkeys.

The 2-14C-deoxyglucose method was used to map local cerebral metabolic activity in monkeys performing a unimanual task requiring visually guided arm reaching and key pressing. The study was carried out with monkeys that either had intact brains or had one hemisphere deprived of visual input by unilateral optic tract section combined in some cases with forebrain commissurotomy. The metabolic mapping revealed activation of sensorimotor cortex only in the hemisphere contralateral to the moving forelimb, irrespective of whether this hemisphere was intact or visually deafferented. These results suggest that visually guided reaching with the forelimb contralateral to the "blind" hemisphere is subserved by that hemisphere's sensorimotor cortex and not by the cortex of the ipsilateral, "seeing" hemisphere. Other areas that were more active metabolically in the "blind" than in the "seeing" hemisphere included the supplementary motor, the secondary somatosensory, and certain posterior parietal cortical areas, intraparietal lateral 5 (lateral 5-ip), 7a, and intraparietal 7 (7-ip). It is suggested that the "blind" hemisphere utilizes at least two distinct pieces of information to guide forelimb movements to visual targets: (1) information about the location of the visual target derived from head and eye movements made to this target and mediated via the inferior parietal cortical areas 7a and 7-ip, and (2) information about the instantaneous upper extremity position derived from forelimb proprioceptive mechanisms and mediated via the somatosensory cortex and thereafter via the superior parietal cortical area, lateral 5-ip.

Bilateral cerebral metabolic effects of pharmacological manipulation of the substantia nigra in the rat: unilateral intranigral application of the putative excitatory neurotransmitter substance P.

The metabolic activity of several anatomically distinct brain areas was investigated by means of the quantitative autoradiographic 2-deoxy-D[1-14C]glucose method in awake rats following unilateral intranigral application of the putative excitatory neurotransmitter substance P. The primary goal was to determine the metabolic effects of substance P on the substantia nigra and its targets. Intranigral injection of 1 mM substance P (1.5 microliters) induced metabolic activation locally in the substantia nigra reticulata by 117% and substantia nigra compacta by 35%, as well as distally in the contralateral substantia nigra reticulata by 22% and contralateral substantia nigra compacta by 21%. All the basal ganglia components, the striatum, pallidum, entopeduncular, subthalamic nucleus and nucleus accumbens displayed bilateral metabolic activations after unilateral intranigral substance P injection. Among the principal reticulata efferent projections, the ventromedial, ventrolateral, parafascicular, mediodorsal and centrolateral thalamic nuclei, as well as the pedunculopontine nucleus displayed bilateral metabolic activations after intranigral substance P application. Moreover, unilateral intranigral substance P injection elicited metabolic activations in the thalamic and cortical components of the reticular, intralaminar, limbic and prefrontal systems, mostly bilateral. It is suggested that substance P applied into one substantia nigra reticulata activates the compacta nigrostriatal dopaminergic and the reticulata nigrothalamic GABAergic outputs inducing distal metabolic effects, similar to those elicited by unilateral nigral electrical stimulation [Savaki et al. (1983) J. comp. Neurol. 213, 46-65] and, opposite to several of those induced by intranigral injection of the inhibitory GABAA agonist muscimol [Savaki et al. (1992) Neuroscience 50, 781-794]. Furthermore, it is suggested that the ipsilateral basal ganglia effects induced by intranigral substance P application are mediated via both the compacta dopaminergic nigrostriatal projection and the reticulata GABAergic nigro-thalamocortico-striatal loop, whereas the contralateral basal ganglia and associated thalamocortical effects are due to the activation of the GABAergic reticulata efferents and are mediated via an interthalamic circuitry involving the motor, reticular and intralaminar thalamic nuclei.

Bilateral cerebral metabolic effects of pharmacological manipulation of the substantia nigra in the rat: unilateral intranigral application of the inhibitory GABAA receptor agonist muscimol.

Rates of cerebral glucose utilization were measured by means of the autoradiographic 2-deoxy-D[1-14C]glucose technique in the rat brain in order to determine the metabolic effects of unilateral intranigral application of the GABAA agonist muscimol upon the substantia nigra and its targets. Intranigral injection of 1.5 microliters 0.3 M muscimol (52 micrograms total dose) induced local metabolic activation in the injected substantia nigra reticulata (by 87% as compared to the control group), and distal metabolic depressions in the nucleus accumbens, striatum, globus pallidus and subthalamic nucleus only ipsilaterally to the injected nigra. The remaining basal ganglia components, including the substantia nigra compacta and the entopeduncular nucleus were bilaterally unaffected. Among the principal efferent projections of the substantia nigra reticulata, the ventromedial and centrolateral thalamic nuclei as well as the deep layers of the superior colliculi were metabolically depressed bilaterally, whereas the ventrolateral, parafascicular and mediodorsal thalamic nuclei as well as the pedunculopontine nucleus displayed metabolic depressions ipsilateral to the muscimol-injection nigra. The ventromedial and centrolateral thalamic nuclei were depressed by 41 and 42%, respectively, in the ipsilateral side, and by 30 and 26% in the contralateral side, when compared to the respective values of the control group of rats. Furthermore, unilateral intranigral injection of 0.3 M muscimol induced metabolic depressions in reticular, intralaminar and prefrontal thalamocortical areas mostly ipsilateral to the injected nigra, as well as in limbic areas bilaterally. It is suggested that the present findings are due to a postsynaptic effect of muscimol on the nigral GABAergic cells and to a consequent metabolic depression of the basal ganglia and associated thalamocortical areas, in contrast to an earlier suggested presynaptic nigral effect of lower doses of intranigrally injected muscimol which induced metabolic activations within the same network. This suggestion is further supported by the fact that intranigrally injected substrate P19 induced similar effects to those elicited by the lower doses of intranigral muscimol and opposite to those induced at present by the higher muscimol dose. Moreover, it is further substantiated that the nigrothalamic GABAergic system is responsible for considerable transfer of information from one substantia nigra reticulata to the ipsilateral basal ganglia and associated thalamocortical components as well as to bilateral motor, intralaminar and limbic areas.

Bilateral alterations in local cerebral glucose utilization following intranigral application of the GABAergic agonist muscimol.

Rates of cerebral glucose utilization were measured by means of the autoradiographic 2-deoxy-D-[1-14C] glucose technique in 70 anatomically discrete central nervous structures in conscious awake rats following unilateral intranigral application of the GABAergic agonist muscimol. Intranigral injection of 1.3 microliters 1 microM muscimol (0.15 ng) induced increases in glucose consumption locally in the substantia nigra reticulata (by 87%), distally in the contralateral reticulata, red nucleus, nucleus accumbens, and prefrontal cortex, and bilaterally in the pyriform cortex, as compared to values in control animals. Intranigral injection of 1.3 microliters 1 mM muscimol (150 ng) effected a local metabolic activation in the substantia nigra reticulata (by 111% compared to the control group) and in compacta (by 18%), as well as a distal activation in the contralateral reticulata (by 39%) and contralateral compacta (by 29%). Beyond the structures affected by the lower dose, the higher dose of muscimol elicited widespread bilateral increases in glucose metabolism in the rat brain. Among the principal nigral reticulata efferent projections, the deep superior colliculi displayed ipsilateral metabolic activation (by 30%), whereas the parafascicular, mediodorsal, and ventromedial thalamic projecting areas, as well as the pedunculopontine nucleus, displayed bilateral activations compared to the control animals. The ventromedial and ventrolateral thalamic nuclei contralateral to the injected substantia nigra reticulata were 20% activated compared to the ipsilateral homologous structures and 30% activated compared to the control rats. The areas that send afferent projections to the reticulata (globus pallidus, entopeduncular and subthalamic nuclei) were mainly activated contralateral to the injected reticulata compared to values for control animals. In general, following intranigral muscimol (1 mM) injection, glucose metabolism was activated to a larger extent on the side contralateral to the injection than on the ipsilateral side. It is suggested that the present findings are due to a presynaptic nigral effect of muscimol on the GABAergic autoreceptors of the striatonigral terminals and to a consequent disinhibition of the reticulata GABAergic output.

Deoxyglucose analysis of the specific topographic functional interrelations between substantia nigra and globus pallidus.

The response of the ipsilateral globus pallidus (GP) to unilateral electrical stimulation of the substantia nigra reticulata (SNr) was studied in the rat, by the autoradiographic [14C]-deoxyglucose method. Different compartments within the GP were metabolically activated, depending on the localization of the electrically stimulated subregions within the SNr. Computer generated, quantified colour coded glucograms were used for the analysis of specific topographic organization of the pallido-nigral functional system. Stimulation of the medial or lateral segments within the SNr induced activation in the medial or lateral compartments of the GP, respectively. Stimulation of the dorsal or ventral subregions within the SNr elicited activation in the ventral or dorsal compartments of the GP, respectively. Activation of the medial or lateral GP compartments was independent of stimulation in the dorsal or ventral SNr segments and vice versa. These results suggest that the topographic interrelations between the substantia nigra and the globus pallidus are characterized by preservation of the mediolateral and inversion of the dorsoventral functional correspondence. The neuronal territory involved into this topographic organization is suggested to consist of the subthalamic and striatal nerve cells projecting collateral axons to both the SNr and the GP.

In vivo release of [3H]gamma-aminobutyric acid in the rat neostriatum--I. Characterization and topographical heterogeneity of the effects of dopaminergic and cholinergic agents.

The release of [3H]gamma-aminobutyric acid continuously synthesized from [3H]glutamine was studied in the striatum of halothane-anaesthetized rats superfused with a push-pull cannula. The levels of spontaneously released [3H]GABA were identical in all striatal regions examined, but were found to be higher at the junction between the striatum and the globus pallidus. Superfusion with a medium enriched in K+ ions induced a concentration-dependent increase in [3H]GABA release. Superfusion with a Ca2+-free medium did not affect the spontaneous outflow of [3H]GABA but sharply reduced the release of [3H]GABA evoked by 30 mM K+. Locally applied tetrodotoxin (50 microM) decreased slightly the spontaneous release of [3H]GABA (-22%). When acetylcholine (50 or 500 microM) was added to a superfusion medium containing eserine (50 microM), the spontaneous release of [3H]GABA was enhanced in the ventral but not in the dorsal region of the striatum. The local application of 2,3,4,5-tetrahydro, 7,8,-dihydroxy, 1-phenyl, 1-H, 3-benzazepine (10 microM), a dopaminergic agonist acting preferentially on D1 receptors increased the release of [3H]GABA in the dorsal striatum (+32%) but decreased it slightly (-19%) in the ventral striatum. 3-(2-(N-3 hydroxyphenylethyl)N-propylamino)ethyl-phenol (50 microM), a preferential D2 receptor agonist, decreased [3H]GABA release when it was applied dorsally (-23%) but not ventrally in the striatum. It is concluded that the regulation of the release of [3H]GABA by acetylcholine and dopaminergic drugs is different in the dorsal and ventral regions of the striatum. These differences may be related to the existence of subpopulations of GABA neurons and may well have functional implications as suggested by behavioural studies.