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The tricarboxylic acid cycle rate (Vtca) and the rate of glutamine synthesis (Vgln) in the pre- and post-MPTP-treated cynomolgus monkey (Macaca fascicularis) brain were measured non-invasively using a 2 Tesla 13C-magnetic resonance spectroscopy (13C-MRS; multislice 1H-13C correlation heteronuclear single quantum coherence spectroscopy) system. Before the infusion of 1-methyl-4-phenyl-1,2,3,6-tertahydropyridine (MPTP) into three monkeys, spectra were obtained by 13C-MRS from each monkey under anesthesia after the bolus injection of [1-13C] glucose (99% atom excess, 0.28 g/kg) followed by the continuous infusion of [1-13C] glucose (99% atom excess, 0.72 g/kg) into the saphenous vein for 3 h. The average values of Vtca were 0.475+/-0.077 (mean+/-S.D.) and 0.472+/-0.073 micromol/g/min, and the average values of Vgln were 0.042+/-0.007 and 0.041+/-0.008 mumol/g/min on the left and on the right hemisphere, respectively. Three monkeys were induced hemiparkinsonism by intracarotid (left) infusion of MPTP (0.6 mg/kg) and then were employed in 13C-MRS studies for 2 (5, 14 days), 3 (3, 8, 71 days) or 4 (5, 11, 27, 78 days) times, respectively, after the MPTP treatment. The average ratios of Vtca and Vgln on the left hemisphere to those on the right hemisphere in pre- and post-MPTP-treated monkeys were 0.837+/-0.085 and 1.373+/-0.132, respectively. These results of non-invasive 13C-MRS analysis of the MPTP primate model of Parkinson's disease indicate that the loss of the dopaminergic innervation from the caudate putamen may modulate the overall glucose metabolism to glutamate and glutamine in the ipsilateral cerebrum.

Direct projections from the amygdala to the cortical masticatory area were found in the macaque monkey. Under the guidance of intracortical microstimulation, retrograde tracers were injected into multiple jaw movement-related regions of the frontal lobe. The cortical masticatory area, especially its principal part, stimulation of which elicited rhythmic jaw movement, was the only site of injection that produced neuronal labeling in the amygdala. The cells of origin of such projections were localized in the medial aspect of the magnocellular division of the basal nucleus through its rostral level. No labeled neurons were observed in the amygdala after tracer injection into any other cortical jaw movement-related region. The present results suggest that the amygdaloid input to the cortical masticatory area may exert some modulatory influence on the generation of masticatory rhythm.

The presupplementary motor area (pre-SMA) is a cortical motor-related area which lies in the medial wall of the frontal lobe, immediately anterior to the supplementary motor area (SMA). This area has been considered to participate in the control of complex forelimb movements in a way different from the SMA. In an attempt to analyze the patterns of projections from the pre-SMA to the basal ganglia, we examined the distributions of pre-SMA inputs in the striatum and the subthalamic nucleus and compared them with the SMA input distributions. To detect morphologically the terminal fields from the pre-SMA and the forelimb region of the SMA, anterograde tracers were injected into such areas that had been identified electrophysiologically in the macaque monkey. Corticostriatal inputs from the pre-SMA were distributed mainly in the striatal cell bridges connecting the rostral aspects of the caudate nucleus and the putamen, as well as in their neighboring striatal portions. These input zones were located, with no substantial overlap, rostral to corticostriatal input zones from the SMA forelimb region. Corticosubthalamic input zones from the pre-SMA were almost localized in the medial aspect of the nucleus, where corticosubthalamic inputs from the SMA forelimb region were also distributed predominantly. However, the major terminal fields from the pre-SMA were centered ventrally to those from the SMA. The present results indicate that the corticostriatal and corticosubthalamic input zones from the pre-SMA appear to be segregated from the SMA-derived input zones. This implies the possibility of parallel processing of motor information from the pre-SMA and SMA in the cortico-basal ganglia circuit., (Copyright 1999 Elsevier Science B.V.)

To investigate the degree of convergence of corticostriatal inputs from the primary motor cortex (MI) and the supplementary motor area (SMA), we analyzed the extent to which corticostriatal inputs from forelimb representations of these motor-related areas spatially overlap in the macaque monkey. Of particular interest was that corticostriatal input zones from SMA overlapped those from MI of the contralateral hemisphere more extensively than from MI of the ipsilateral hemisphere., (Copyright 1998 Elsevier Science B.V.)

Employing anterograde axonal tracing combined with intracortical microstimulation, we have revealed in the macaque monkey that the orofacial region of the primary motor cortex sends projection fibers to the deep layers of the superior colliculus. The terminal site of these projection fibers was almost localized to the lateral part of the intermediate gray layer at its rostral level, and spatially segregated from that of projection fibers arising from the frontal eye field. The results indicate the existence of a discrete tectal region related specifically to the control of orofacial movements.

Direct projections from the superior colliculus to the subthalamic nucleus were found in the rat in antero- and retrograde tracing experiments; these projections arose mainly from the deep layers of the superior colliculus at its middle to caudal levels. The present findings suggest that signals from the deep layers of the superior colliculus may modulate the basal ganglia activity during orienting behavior.

The magnocellular reticular nucleus (MRN) of the cat was observed electron microscopically following the combined application of kainic acid into the pedunculopontine tegmental nuclear region (PPN region) and horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP) into the spinal cord. Some degenerating axon terminals arising from the PPN region were found to make synaptic contacts with retrogradely HRP-labeled reticulospinal neurons in the MRN.

The cross-sectional area of cholinergic neurons stained immunohistochemically for choline acetyltransferase were measured in the striatum of infants, young adults, aged individuals and patients with Alzheimer's disease. Cholinergic neurons were distributed throughout the caudate nucleus and the putamen and displayed no significant variations in size across the two structures. The cross-sectional area of striatal cholinergic neurons was smaller in infants as compared with all other groups examined. No significant changes were observed in the size of these neurons as a consequence of aging or Alzheimer's disease.

The synaptic organization of the feline pedunculopontine tegmental nucleus (PPN) was studied electron microscopically. The bouton covering ratios were calculated in various sizes of PPN neurons, and the ratios of large neurons (56%) were found to be much higher than those of small neurons (16%). The PPN neuron dendrites usually showed some varicosities, and spines were observed on both somatic and dendritic profiles. Among a total of 1021 synapses sampled at random, axosomatic, axodendritic and axospinous synapses comprised 21.7, 61.2 and 14.1%, respectively. On the basis of the postsynaptic junction, these synapses were classified into the symmetric (66.3%) and the asymmetric (33.7%) types. The percentage of symmetric synapses was much higher on the soma (91.0%), and the large (69.4%) and medium-sized (63.2%) dendrite, while that of asymmetric synapses showed a higher value on the small dendrite (55.5%) and the dendritic spine (50.8%). Axoaxonic, dendrodendritic and dendroaxonic synapses, although not so frequent, were, in part, involved in the serial synapse or the synaptic triad. It is concluded that some PPN neurons are spiny, and that axosomatic, axodendritic and axospinous synapses are the main synaptic constituents and besides those synapses a more complex synaptic organization exists in this nucleus.

A retrograde tracing study in the mole using wheat germ-agglutinated horseradish peroxidase (WGA-HRP) indicated that the medial superior olivary nucleus (MSO) projects to the inferior colliculus (IC) bilaterally. Considering the strict ipsilateral projections from the MSO to the IC in all other eutherian species ever reported, the bilateral projection in the mole is quite unique. This may reflect specializations of the peripheral auditory apparatus of the underground dwellers and/or primitiveness of the insectivorous brains.

The cat substantia nigra (SN) pars reticulata (SNR) has been observed electron microscopically after ibotenic acid injections into the caudate nucleus (Cd) and horseradish peroxidase injections into the nucleus tegmenti pedunculopontinus pars compacta (TPC). As a result, degenerating striatal terminals were found to make symmetric synaptic contacts on retrogradely labeled SNR neurons. The present findings, together with our previous study on the tegmentonigrostriatal projection (Tokuno et al., Neurosci. Lett. 85 (1988) 1-4), confirm that the Cd has indirect reciprocal connections with the TPC via the SN.

The relationships between nigrotectal terminals and tectospinal neurons in the deep layers of the superior colliculus have been examined light and electron microscopically by using antero- and retrograde transport of tracer, and anterograde degeneration. For light microscopy, horseradish peroxidase (HRP) was injected into the cervical spinal cord, and HRP conjugated to wheat germ agglutinin (WGA-HRP) into the substantia nigra at the same time. It appeared that about 22% of the retrogradely labeled tectospinal neurons were totally or partially in the anterogradely labeled nigral terminal clusters. This coexistence was particularly manifest in the dorso-lateral part of the intermediate gray layer. For electron microscopy, nigral lesions and HRP injections into the cervical spinal cord were combined in the same animals. Degenerating nigrotectal terminals were found in both axosomatic and axodendritic symmetrical synaptic contacts with retrogradely labeled tectospinal neurons in the intermediate gray layer. Present experiments show tectospinal neurons receiving monosynaptic input from the substantia nigra do exist in the intermediate gray layer of the superior colliculus, especially in its dorsolateral portion.

The neuronal connections of the anterior pretectal nucleus (PTA) were investigated in the cat. For the light microscopy, the retrograde double-labeling technique by means of Fluoro-Gold (FG) and horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP) was used. Following injections of one tracer into the central lateral nucleus of the thalamus (CL) and the other into the dorsal accessory olivary nucleus (DAO), distributions of labeled neurons in the PTA were observed. Most of the labeled neurons were single-labeled either with FG or with WGA-HRP. The result indicated that pretecto-thalamic projection neurons were distributed throughout the whole extent of the PTA, whereas pretecto-olivary projection neurons were located in a restricted area of the ventral part of the PTA. Only a very small number of double-labeled neurons were found in the PTA. These two efferent projections thus seemed to be derived from different populations of PTA neurons. For the electron microscopy, a combination of retrograde transport of horseradish peroxidase (HRP) and anterograde degeneration technique was used. After HRP injections into the CL combined with lesions either in the motor cortex (MCx) or in the anterior interpositus nucleus of the cerebellum (Cbl), some degenerating axon terminals originating from the cerebrum or cerebellum were found to synapse with retrogradely labeled pretecto-thalamic projection neurons. We have already observed direct cerebral and cerebellar projections to the pretecto-olivary projection neurons (J. Comp. Neurol., 259 (1987) 348-363). We conclude that the two different populations of PTA neurons comprise two different kinds of neuronal circuitries, i.e. MCx-PTA-CL-MCx and Cbl-PTA-DAO-Cbl, and that these two circuitries might interrelate with each other in the PTA at the cellular level.

Pallidal terminals in the cat lateral habenular nucleus and the ventral anterior and ventral lateral nuclear complex of the thalamus have been examined electron microscopically. A significant difference was obtained after a quantitative analysis of size and shape parameters of synaptic vesicles in the identified terminals: synaptic vesicles in the pallidohabenular terminals had smaller mean elongation index and larger mean vesicle profile area than those in the pallidothalamic terminals.