Prefrontal cortical cells projecting to the supplementary eye field and presupplementary motor area in the monkey

We examined the location and spatial distribution of prefrontal cortical (PF) cells projecting to the supplementary eye field (SEF) and presupplementary motor area (pre-SMA) using a double retrograde-labeling technique in monkeys (Macaca fuscata). The SEF and pre-SMA were physiologically identified based on the findings of intracortical microstimulation and single cell recordings. Two fluorescent tracers, diamidino yellow and fast blue, were injected into the SEF and pre-SMA of each monkey. Retrogradely labeled cells in the PF were plotted with an automated plotting system. The cells projecting to the SEF and pre-SMA were mainly distributed in the upper and lower banks of the principal sulcus (area 46), with little overlap. Cells projecting to the SEF, but not to the pre-SMA, were observed in areas 8a, 8b, 9, 12, and 45. These findings suggest that the SEF and pre-SMA receive different sets of information from the PF cells.     

Distinct afferents to internal and external pallidal segments in the squirrel monkey

The use of retrograde fluorescence double-labeling method has revealed that the internal (GPi) and external (GPe) segments of globus pallidus in squirrel monkey receive projections from different cell populations in striatum and subthalamic nucleus. Striatal neurons projecting either to GPi or GPe formed wide and nonoverlapping cell bands oriented obliquely and covering large portions of putamen and caudate nucleus. Subthalamic neurons projecting to GPe were more abundant and more laterally located than those projecting to GPi. A few cells branching to GPi and GPe were found in subthalamic nucleus but not in striatum. Thus, different striatal and subthalamic neuronal populations influence GPi and GPe in primates.     

Excitatory cortical inputs to pallidal neurons via the subthalamic nucleus in the monkey

How the motor-related cortical areas modulate the activity of the output nuclei of the basal ganglia is an important issue for understanding the mechanisms of motor control by the basal ganglia. In the present study, by using awake monkeys, the polysynaptic effects of electrical stimulation in the forelimb regions of the primary motor and primary somatosensory cortices on the activity of globus pallidus (GP) neurons, especially mediated by the subthalamic nucleus (STN), have been characterized. Cortical stimulation induced an early, short-latency excitation followed by an inhibition and a late excitation in neurons of both the external and internal segments of the GP. It also induced an early, short-latency excitation followed by a late excitation and an inhibition in STN neurons. The early excitation in STN neurons preceded that in GP neurons. Blockade of STN neuronal activity by muscimol (GABA(A) receptor agonist) injection resulted in abolishment of both the early and late excitations evoked in GP neurons by cortical stimulation. At the same time, the spontaneous discharge rate of GP neurons decreased, pauses between the groups of spikes of GP neurons became prominent, and the firing pattern became regular. Injection of (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) [N-methyl-D-aspartate (NMDA) receptor antagonist], but not 1,2,3, 4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium [NBQX (non-NMDA receptor antagonist)], into the STN attenuated the early and late excitations in GP neurons, suggesting that cortico-subthalamic transmission is mediated mainly by NMDA receptors. Interference with the pallido-subthalamic transmission by bicuculline (GABA(A) receptor antagonist) injection into the STN made the inhibition distinct without affecting the early excitation. The present results indicate that the cortico-subthalamo-pallidal pathway conveys powerful excitatory effects from the motor-related cortical areas to the GP with shorter conduction time than the effects conveyed through the striatum.     

Spinal pathways projecting to the cerebral first somatosensory area in the monkey

1. Potentials evoked with short latency in the cerebral post-central gyrus after intradermal electrical, or adequate light tactile stimulation of the contralateral body half have been studied in the monkey, before and after transection of different spinal pathways at the upper cervical level.2. Initially, positive potentials evoked by both types of stimulus were recorded after transection of the dorsal funiculi with the same somatotopic, topographical distribution as before the lesion.3. The potentials recorded after transection of the dorsal funiculi could be evoked via one pathway located in the dorsal half of the lateral funiculus ipsilateral to the afferent input, and another pathway located, at least partially, in the ventral funiculus contralateral to the afferent input.4. Of these two pathways, the crossed ventral pathway was found necessary to keep the topographical distribution of the evoked potentials unaltered.     

Short-latency peripheral inputs to thalamic neurones projecting to the motor cortex in the monkey

Summary One hundred seventy-five neurones in the n.ventroposterior lateralis (VPL) and n.ventralis lateralis (VL) in the thalamus of anaesthetised monkeys have been tested antidromically for projection to the cortex and for somatosensory input from the contralateral arm.Using bipolar stimulation of the cortical surface, 113 thalamic neurones were successfully identified as antidromically driven from the hand area of the postcentral gyrus (48 neurones) or from the hand area of the precentral gyrus (65 neurones). All but one of these 113 neurones could only be antidromically discharged from the postcentral cortex or from the precentral cortex, and not from both. Most had antidromic latencies between 0.5 and 1.5 ms.Twenty-five/sixty-five precentrally projecting neurones and 45/48 postcentrally projecting neurones were activated by stimulation of the contralateral median or radial nerves. Both groups responded at short latency (4–8 ms) and many were activated by low-threshold shocks (0.8–1.3 T) and had restricted receptive fields on the hand. Precentrally projecting neurones responded most powerfully to joint movement or deep pressure, and some of these neurones were also responsive to cutaneous stimuli.Precentrally projecting neurones with peripheral inputs were all found in the oral subdivision of the VPL (the VPL_o). The properties of these neurones suggest that they may be partly responsible for rapid somatosensory input to the motor cortex.     

Activity of monkey frontal eye field neurons projecting to oculomotor regions of the pons.

1. This study identified neurons in the rhesus monkey's frontal eye field that projected to oculomotor regions of the pons and characterized the signals sent by these neurons from frontal eye field to pons. 2. In two behaving rhesus monkeys, frontal eye field neurons projecting to the pons were identified via antidromic excitation by a stimulating microelectrode whose tip was centered in or near the omnipause region of the pontine raphe. This stimulation site corresponded to the nucleus raphe interpositus (RIP). In addition, electrical stimulation of the frontal eye field was used to demonstrate the effects of frontal eye field input on neurons in the omnipause region and surrounding paramedian pontine reticular formation (PPRF). 3. Twenty-five corticopontine neurons were identified and characterized. Most frontal eye field neurons projecting to the pons were either movement neurons, firing in association with saccadic eye movements (48%), or foveal neurons responsive to visual stimulation of the fovea combined with activity related to fixation (28%). Corticopontine movement neurons fired before, during, and after saccades made within a restricted movement field. 4. The activity of identified corticopontine neurons was very similar to the activity of neurons antidromically excited from the superior colliculus where 59% had movement related activity, and 22% had foveal and fixation related activity. 5. High-intensity, short-duration electrical stimulation of the frontal eye field caused omnipause neurons to stop firing. The cessation in firing appeared to be immediate, within < or = 5 ms. The time that the omnipause neuron remained quiet depended on the intensity of the cortical stimulus and lasted up to 30 ms after a train of three stimulus pulses lasting a total of 6 ms at an intensity of 1,000 microA. Low-intensity, longer duration electrical stimuli (24 pulses, 75 microA, 70 ms) traditionally used to evoke saccades from the frontal eye field were also followed by a cessation in omnipause neuron firing, but only after a delay of approximately 30 ms. For these stimuli, the omnipause neuron resumed firing when the stimulus was turned off. 6. The same stimuli that caused omnipause neurons to stop firing excited burst neurons in the PPRF. The latency to excitation ranged from 4.2 to 9.8 ms, suggesting that there is at least one additional neuron between frontal eye field neurons and burst neurons in the PPRF. 7. The present study confirms and extends the results of previous work, with the use of retrograde and anterograde tracers, demonstrating direct projections from the frontal eye field to the pons.(ABSTRACT TRUNCATED AT 400 WORDS)     

Activity and distribution patterns of monkey pallidal neurons in response to peripheral nerve stimulation

The response patterns of pallidal neurons to electrical stimulation of the median and tibial nerves were examined in awake monkeys. Around 30% of the recorded neurons responded to the stimulation of either the median or tibial nerve, while only 6% responded to the stimulation of both nerves. The vast majority of these pallidal neurons displayed monophasic excitation or monophasic inhibition. The latency of the excitation was shorter than that of the inhibition. In each pallidal segment, the neurons responding to the median nerve stimulation (representing the forelimb) tended to be located ventral to those responding to the tibial nerve stimulation (representing the hindlimb). The present results indicate that the somatotopical arrangement in the globus pallidus can be outlined based on the neuronal responses to peripheral nerve stimulation.     

Characteristics of near response cells projecting to the oculomotor nucleus.

1. Previous work has shown neurons just dorsal and lateral to the oculomotor nucleus that increase their firing rate with increases in the angle of ocular convergence. It has been suggested that the output of these midbrain near response cells might provide the vergence command needed by the medial rectus motoneurons. However, lens accommodation ordinarily accompanies convergence, and a subsequent study showed that only about one-half of these midbrain near response cells carried a signal related exclusively to vergence. One hypothesis suggested by this finding is that this subgroup of neurons might have a unique role in providing a "pure" vergence signal to the medial rectus motoneurons. 2. In the present study extracellular recordings were made from midbrain near response cells in monkeys while eye position and lens accommodation were measured. The monkeys viewed targets through an optical system that allowed the accommodative and ocular vergence demands to be manipulated independently. This approach was used to produce a partial dissociation of accommodative and vergence responses, so that an accommodative and vergence coefficient could be determined for each cell, by the use of the following equation FR = R0 + kda x AR + kdv x CR where FR is the firing rate of the near response cell, R0 is the predicted firing rate for a distant target, kda is the (dissociated) accommodation coefficient, AR is the accommodative response, kdv is the (dissociated) vergence coefficient, and CR is the convergence response. 3. The vergence and accommodation coefficients were determined for a large number of midbrain near response cells, including a subset that could be antidromically activated from the medial rectus subdivisions of the oculomotor nucleus. Some near response neurons were found with signals related exclusively to convergence (i.e., kdv greater than 0 and kda = 0), whereas several others had signals related exclusively to lens accommodation (i.e., kda greater than 0 and kdv = 0). The majority of the near response cells had signals related to both responses (i.e., kda not equal to 0 and kdv not equal to 0). Furthermore, the vergence and accommodation coefficients of near response cells appeared to be continuously distributed. Some cells had negative accommodation or vergence coefficients. 4. The 17 near response cells that could be antidromically activated from the oculomotor nucleus presumably provide vergence signals to the medial rectus motoneurons. Although all had positive vergence coefficients, only four of these cells carried signals that were related exclusively to vergence.(ABSTRACT TRUNCATED AT 400 WORDS)     

Identification of cone mechanisms in monkey ganglion cells

1. Blue, green, and red sensitive cone mechanisms have been studied in two types of on-centre ganglion cells in the Rhesus monkey's retina.2. One type of cell receives signals from both green and red sensitive cone mechanisms, both of which excite in the centre and inhibit in the periphery of the cell's receptive field. These cells discharge transiently to maintained stimuli of any wave-length and are called phasic.3. The second type of cell receives excitatory signals from only one cone mechanism, either blue, green or red sensitive, in the centre, and inhibition from another cone mechanism in the periphery of its receptive field. These cells discharge continuously to maintained stimuli of appropriate wave-length and are called tonic.4. Tonic cells outnumber phasic cells although both are found adjacent to one another throughout the retina. Phasic cells are relatively more common toward the periphery and tonic cells relatively more common toward the fovea.     

A quantitative analysis of pallidal discharge during targeted reaching movement in the monkey

Summary Neurons in the globus pallidus have been studied during reaching movements of the arm made at varying speeds. The reaching task is similar to one used in earlier experiments, in which disruption of normal pallidal output caused changes in movement time. The pallidal cells studied were those that showed task-related changes in activity and a modification of discharge when the arm was manipulated outside of the task. Neuronal discharge was assessed to evaluate two possible models, one in which the timing of task-related discharge varied as a function of movement time and the other in which the amplitude (mean firing rate) of the change in discharge varied as movement time varied. The relation between neuronal discharge and movement time was examined quantitatively on a trial-by-trial basis using a statistical algorithm that identified each phase of the change in neuronal discharge on each trial. A nonparametric statistic was used to determine the correlation between movement time and the duration or latency of changes in neural firing or the mean discharge during each phase of the cell's response. For fifty-five percent of the 40 neurons studied, the timing of the cell's response (duration or latency) varied as a function of movement time. For only 10 cells (25%) was there a significant correlation between movement time and the mean firing rate during one or more phases of the cell's response. Both timing and frequency modulation with movement time were limited to cells responsive to manipulation at the wrist or the shoulder.     

Impulse conduction properties of noradrenergic locus coeruleus axons projecting to monkey cerebrocortex

Antidromically driven action potentials were recorded from norepinephrine-containing locus coeruleus neurons in response to electrical stimulation of cerebrocortical and thalamic areas in anesthetized squirrel monkeys. These cells reliably conducted impulses from cortical sites of distances up to 100 mm from locus coeruleus. Monkey locus coeruleus neurons were found to exhibit several properties previously described for these cells in rat, including slow spontaneous discharge rates, characteristic impulse waveforms, antidromic activation from many target areas, a period of suppressed activity following either antidromic or orthodromic driving and responsiveness to noxious stimuli presented as subcutaneous electrical stimulation of a rear foot. However, a large population of monkey locus coeruleus neurons was found to exhibit more rapid conduction velocities than previously found for rat (e.g. approximately 34% were greater than 1 m/s), resulting in similar conduction latencies to distant target areas in the two species. This indicates that the conduction times required for locus coeruleus impulses to reach distant target areas may be conserved across different species and sizes of brains, suggesting that these latencies play an important role in the general function of the locus coeruleus system in brain and behavioral processes.     

Projection on the motor cortex of thalamic neurons with pallidal input in the monkey

Summary The cortical projection areas of thalamic neurons with basal ganglia and/or cerebellar inputs were studied electrophysiologically in unanesthetized monkeys. Thalamic neurons which receive inhibition from the pallidum were found to project to the motor cortex (area 4) as well as to premotor cortex. The neurons with pallidal input and motor cortical projection were located mainly in VLo. This result indicates that the basal ganglia innervate the motor cortex through the thalamus. Thus the basal ganglia can modify the cortical output for controlling movements directly through this pathway as compared with its influence through the prefrontal and premotor cortices.     

Identification of all GABA-immunoreactive neurons projecting to the lobster stomatogastric ganglion

Summary The stomatogastric ganglion of lobsters (Homarus or Jasus) contains a large number of gamma-aminobutyric acid-immunoreactive processes originating from ten fibres in the single input nerve, the stomatogastric nerve. The cell bodies and axonal pathways of these ten fibres have been identified using gamma-aminobutyric acid immunohistochemistry in combination with Lucifer Yellow staining (double labelling) and nickel chloride backfilling (selective gamma-aminobutyric acid immunoinhibition).It is shown that eight gamma-aminobutyric acid-immunoreactive neurons project to the stomatogastric ganglion: gamma-aminobutyric acid neurons 1 and 2, found posterior to the oesophageal ganglion, entering the stomatogastric nerve via the oesophageal nerve as well as sending an axonal branch into each superior oesophageal nerve; gamma-aminobutyric acid neurons 3 and 4, found anterior to the oesophageal ganglion, each sending an axonal branch into each inferior oesophageal nerve to reach the stomatogastric nerve via the commissural ganglion and the superior oesophageal nerve; and gamma-aminobutyric acid neurons 5 and 6, found in each commissural ganglion, projecting into the stomatogastric nerve via the inferior oesophageal nerve, the oesophageal ganglion and the oesophageal nerve.These gamma-aminobutyric acid-immunoreactive neurons were also characterized by electrophysiological methods coupled with Lucifer Yellow labelling, and their picrotoxin-sensitive effects on several stomatogastric ganglion neurons were demonstrated.The present results provide a firm basis for further studies concerning the physiological significance of one class of neurochemically-defined input neurons to stomatogastric ganglion networks.     

Activity of identified wrist-related pallidal neurons during step and ramp wrist movements in the monkey

1. The activity of globus pallidus (GP) neurons (n = 1,117) was studied in two monkeys to reexamine the relation of neuronal activity to movement type (slow vs. fast) while they performed both a visually guided step and ramp wrist tracking task. To select neurons specifically related to wrist movements, we employed both a somatosensory examination of individual body parts and a statistical analysis of the strength of temporal coupling of neuronal discharges to active wrist movement. 2. Neuronal responses to somatosensory stimulation were studied in 1,000 high-frequency GP neurons, of which 686 exhibited clear responses to manipulation of body parts. Of the latter, 336 responded to passive manipulation of forelimb joints and 58 selectively to passive flexion or extension of the wrist. 3. In the external segment of GP (GPe), most neurons responding to passive wrist movement were found to be clustered in four to five adjacent, closely positioned (separated by 200 microns) tracks in single coronal planes. The clusters were irregular in shape with a maximal width of 800-1,000 microns. Separate clusters of neurons responsive to passive wrist movement were identified in planes 3 mm apart in one monkey and in planes 500 microns apart in the other. Multiple clusters of neurons were also found for neurons responsive to joints other than the wrist. These findings suggest a more discrete and complex representation of individual joints in the primate GP than previously conceived. 4. During the performance of the wrist flexion and extension task, 92 neurons showed clear and consistent changes in activity. For these neurons we measured, with a statistical method on a trial-by-trial basis, the strength of temporal coupling between the onset of active wrist movement and the onset of change in neuronal discharge rate. Fifteen neurons showed changes in activity time-locked to the onset of active wrist movement. 5. Twelve pallidal neurons were classified as "wrist-related" based on their movement-locked changes in discharge during task performance and their clear responses to passive wrist joint rotation on examination. All of these neurons exhibited statistically significant modulation of their discharge rate during both fast (peak velocity 97-205 degrees/s) and slow (peak velocity 20-62 degrees/s) wrist movements in the task. The amplitudes of modulation were larger during fast wrist movement than slow movement. These results suggest that the basal ganglia motor circuit plays a similar, rather than an exclusive, role in the control of slow and fast limb movements.     

Distribution of granule cells projecting to focal Purkinje cells in mouse uvula-nodulus

Mossy and climbing fibers convey a broad array of signals from vestibular end organs to Purkinje cells in the vestibulo-cerebellum. We have shown previously that Purkinje cell simple spikes (SSs) and climbing fiber-evoked complex spikes (CSs) in the mouse uvula-nodulus are arrayed in 400 mum wide sagittal climbing fiber zones corresponding to the rotational axes of the vertical semicircular canals. It is often assumed that mossy fibers modulate a higher frequency of SSs through the intermediary action of granule cells whose parallel fibers course through the Purkinje cell dendritic tree. This assumption is complicated by the diffuse topography of vestibular primary afferent mossy fiber projections to the uvula-nodulus and the dispersion of mossy fiber signals along folial axes by parallel fibers. Here we measure this parallel fiber dispersion. We made microinjections of neurobiotin into the molecular layers of different folia within the mouse vestibulo-cerebellum and measured the distribution of granule cells retrogradely labeled by the injected neurobiotin. Sixty-two percent of labeled granule cells were located outside a 400 mum sagittal zone flanking the injection site. The dispersion of labeled granule cells was approximately 2.5 mm along folial axes that were 2.7-2.9 mm wide. Our data suggest that topographic specificity of SSs could not be attributed to the topography of vestibular primary afferent mossy fiber-granule cell projections. Rather the response specificity of SSs must be attributed to other mechanisms related to climbing fiber-evoked Purkinje cell and interneuronal activity.     

Spatial distribution of cingulate cells projecting to the primary, supplementary, and pre-supplementary motor areas: a retrograde multiple labeling study in the macaque monkey

We examined the location and spatial distribution of cingulate cortical cells projecting to the forelimb areas of the primary motor cortex (MI), supplementary motor area (SMA), and pre-supplementary motor area (pre-SMA) using a multiple retrograde labeling technique in the monkeys (Macaca fuscata). The forelimb areas of the MI, SMA and pre-SMA were physiologically identified, based on the findings of intracortical microstimulation (ICMS) and single cell recording. Three different tracers, diamidino yellow (DY), fast blue (FB), and wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP), were injected into each of the three motor areas in the same monkey. Retrogradely labeled cells in the cingulate cortex were plotted with an automated plotting system. Cells projecting to the forelimb area of the MI were distributed in the two separate regions situated rostrocaudally in the dorsal and ventral banks of the cingulate sulcus, namely the rostral cingulate motor area (CMAr) and caudal cingulate motor area (CMAc). These two regions corresponded to the forelimb areas identified by the ICMS in the same animal. The distribution of projection cells to the SMA overlapped extensively with that of projection cells to the MI. Although the MI received relatively sparse inputs from the CMAr than from the CMAc, the SMA received inputs from the CMAr and its adjacent areas as much as from the CMAc. The projection cells to the pre-SMA were distributed in the anterior portion of the cingulate cortex, including the anterior part of the CMAr and in a small part of the cingulate gyrus. These findings indicate that the MI and SMA share a considerable common information from the cingulate cortex, including the CMAr and CMAc, whereas the pre-SMA receives a different set of information from the anterior part of the cingulate cortex.     

Identification of brainstem interneurons projecting to the trigeminal motor nucleus and adjacent structures in the rabbit

Neurons of several nuclei within the medial pontomedullar reticular formation are active during mastication, but their relationship with other elements of the pattern generating circuits have never been clearly defined. In this paper, we have studied the connection of this area with the trigeminal motor nucleus and with pools of last-order interneurons of the lateral brainstem. Retrograde tracing techniques were used in combination with immunohistochemistry to define populations of glutamatergic and GABAergic neurons. Injections of tracer into the Vth motor nucleus marked neurons in several trigeminal nuclei including the ipsilateral mesencephalic nucleus, the contralateral Vth motor nucleus, the dorsal cap of the main sensory nucleus and the rostral divisions of the spinal nucleus bilaterally. Many last-order interneurons formed a bilateral lateral band running caudally from Regio h (the zone surrounding the Vth motor nucleus), through the parvocellular reticular formation and Vth spinal caudal nucleus. Injections of tracer into Regio h, an area rich in last-order interneurons, marked, in addition to the areas listed above, a large number of neurons in the medial reticular formation bilaterally. The major difference between injection sites was that most neurons projecting to the Vth motor nucleus were located laterally, whereas most of those projecting to Regio h were found medially. Both populations contained glutamatergic and GABAergic neurons intermingled. Our results indicate that neurons of the medial reticular formation that are active during mastication influence Vth motoneurons output via relays in Regio h and other adjacent nuclei.     

GABAergic and catecholaminergic innervation of mediobasal hypothalamic beta-endorphin cells projecting to the medial preoptic area.

In the absence of cellular estrogen receptors or proven direct estrogen action in the rat, it is assumed that estrogen indirectly regulates the secretory activity of the preoptic area luteinizing hormone-releasing hormone-producing cells. We have previously shown that pro-opiomelanocortin neurons in the arcuate nucleus of the rat send axons rostrally to connect with luteinizing hormone-releasing hormone neurons of the preoptic area. An experiment combining retrograde tracing and double-immunostaining was used to test the hypothesis that rat GABAergic and/or catecholaminergic neurons can influence luteinizing hormone-releasing hormone-producing cells via mediobasal hypothalamic beta-endorphin neurons. The retrograde tracer horseradish peroxidase was injected into the medial preoptic area; two days later, arcuate nucleus Vibratome sections were double-immunostained for beta-endorphin and glutamate decarboxylase or tyrosine hydroxylase. Light and electron microscopic analysis of these triple-labeled sections demonstrated that a population of beta-endorphin-immunoreactive neurons concentrated in the ventromedial arcuate nucleus contain retrogradely transported horseradish peroxidase granules and form synaptic contacts with glutamate decarboxylase- and tyrosine hydroxylase-immunoreactive axon terminals. The present data suggest that arcuate nucleus GABA and catecholamine fibers may influence luteinizing hormone-releasing hormone-containing neurons via projective pro-opiomelanocortin cells.