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H Nishijo

Publications and source records attributed to H Nishijo.

At least 55 records · Page 3Linked to original sources

Physiological results of monkey brain ischemia, and protection by a calcium blocker.

Physiological and histological investigation was undertaken to examine dynamic and metabolic changes due to transient ischemic insult of the monkey brain with and without postischemic treatment by the calcium entry blocker, NC-1100 (1 mg/kg, IV). Monkeys were subjected to temporary occlusion of the eight major arteries: bilateral common carotid, internal and external carotid, and vertebral arteries. Blood flow was restored after 5-, 10-, 13-, and 15-min ischemia in different monkeys. The amplitudes of extradural, cortical, and hippocampal electroencephalograms decreased severely within 1-6 min after beginning occlusion. Complete recovery of these electroencephalograms required more than 1 h. During ischemia, significant change was obvious in arterial glucose, and systolic, diastolic, and mean blood pressure, all of which increased. There were no significant physiological differences between the untreated and NC-1100-treated groups, except decreased diastolic blood pressure and slightly lower postischemic heart rate in the treated group. These small differences might be accounted for by the effect of the calcium blocker. Ten to 15 minutes ischemia caused cell changes, including cell death, which were confined almost exclusively to the CA1 subfield of untreated hippocampi examined the fifth day after occlusion. However, no ischemia-induced cell change was observed in the CA1 subfield of hippocampi subjected to 10 to 15 min ischemia in the NC-1100-treated group. It was concluded that a calcium entry blocker can protect neurons from mild ischemia-induced injury and might ameliorate morphological damage and functional impairment of the brain due to ischemia in patients who suffer transient anoxic or hypoxic injury. The present physiological data should contribute to their clinical treatment.

Analysis of Variance↗

Ischemic neuronal damage specific to monkey hippocampus: histological investigation.

We previously reported lesions confined specifically to the hippocampus when produced by occluding eight vessels (the bilateral vertebral, common, internal, and external carotid arteries), which supply blood to the brain. However, histopathological changes in the primate brain, caused by ischemic injury, have not previously been thoroughly investigated. In the present study, macaque monkeys were subjected to 5-18-min ischemia by occluding the eight vessels. After the brains were perfused and fixed 5 days after the occlusion, all regions were histologically investigated for ischemic cell changes. Ischemia for 5 min produced no ischemic cell change. Ischemia for 10-15 min produced cell death limited to the deeper portion of the pyramidal cell layer of the CA1 subfield in the hippocampus. In most monkeys, no cell death was observed in any brain region outside of the hippocampus after ischemia for up to 15 min. Ischemia for 18 min produced more widespread cell death in the CA1 subfield of the hippocampus, and cell death was no longer confined to the hippocampus, but was observed in layers III, V, and VI of the neocortices, the striatum, and some other regions. Brains that were perfused and fixed 1 year after 15-min ischemic insult revealed no ischemic cell morphological change in any region, but the number of pyramidal cells in the CA1 subfield was decreased to about half. The results indicate that the CA1 subfield of the monkey hippocampus is the precise region of the brain most susceptible to ischemic insult in the primate forebrain, and after a critical time (15-min ischemia in this procedure) ischemic cell changes occur suddenly and extensively. Ischemia due to occlusion of eight arteries for 10-15 min could produce a model of human amnesia caused by transient ischemic insult.

Amnesia↗

Functional image-guided neurosurgical simulation system using computerized three-dimensional graphics and dipole tracing.

This report describes a preoperative simulation and intraoperative localization system for use with three-dimensional functional images in intracranial surgery. The system, which produces three-dimensional functional images by superimposition of the generators of somatosensory evoked potentials derived from dipole tracing, was applied in the preoperative localization of central sulci in 12 patients with intracranial disorders. The preoperative localization of central sulci was assessed by intraoperative cortical recording of somatosensory evoked potentials in three patients. In six patients, three-dimensional computer graphics were reconstructed from magnetic resonance images and allowed visualization of the lesions through the semitransparent views of the scalp surface and the brain. The three-dimensional functional images were created by superimposing the generators of somatosensory evoked potentials on three-dimensional computer graphics. This combined technique provided preoperative data regarding the three-dimensional relationship between the sensorimotor cortex and the lesions. We also developed a three-dimensional digitizer that incorporates a mechanical arm and a laser pointer for use in integrating information obtained in the preoperative simulation into the surgical field. Intraoperative localization can be performed in real time on the three-dimensional computer graphics in combination with the functional images created from dipole tracing. This system was applied in five patients who underwent surgical brain tumor resections with minimal damage to the normal brain tissue. The use of this system for stereotactic craniotomy increased the safety of the surgery by affording preoperative simulation and intraoperative localization with the three-dimensional functional images. Two illustrative case reports are presented.

Brain Diseases↗

Neuronal activity in the primate hippocampal formation during a conditional association task based on the subject's location.

The hippocampal formation (HF) functions in two domains of memory: spatial and nonspatial associative memory. The HF includes the hippocampus proper, the dentate gyrus, and the subicular complex. Studies of spatial correlates of HF neuronal activity have revealed that a subject's location in space can impose critical constraints on patterns of neuronal activity in the HF. This report compares monkey HF neuronal responses in two kinds of stimulus-response association tasks (go/no-go tasks with symmetrical reinforcement). In a place-dependent, conditional, stimulus-response association (PCA) task, the subject's location was the condition upon which stimulus (object)-behavioral response association depended. In a place-in-dependent, simple, stimulus-response association (ISA) task, the object-behavioral response contingency was independent of the subject's location. Of 329 neurons recorded, the activity of 88 increased or decreased significantly in response to the presentation of an object during the PCA task. Responses of 17 neurons depended differentially on specific combinations of object, place, and behavior in the PCA task (specific-combination neurons). These specific-combination responses do not simply reflect object-behavioral response association in the PCA task, since neuronal responses in the same object-behavioral response association were not restored in the ISA task in which there was no dependence on the subject's location. This suggests the influence of location on HF neuronal responses in object-behavioral response association when the subject's location is imposed as a condition. Responses of 12 neurons differentiated the kind of object in the PCA task (object-differential neurons). In the ISA task, most object-differential responses diminished or disappeared. Since the HF object-differential responses elicited by the conditions imposed by the PCA task. Characteristics of the two neuron types suggest that HF neurons encode both stimulus percept and attributes such as the place where the stimulus is presented and the conditional relation imposed in the task.

Animals↗

Place and contingency differential responses of monkey septal neurons during conditional place-object discrimination.

To elucidate spatial and cognitive function of the septal nuclei, neural activity was recorded from alert monkeys during performance of a place-dependent go/no-go (PGN) task. Response/reinforcement contingencies of given objects were conditional upon the location of a motorized, movable device (cab) containing a monkey in one of four places. The task was initiated by presentation of the outside view (place phase) followed by presentation of an object (object phase) selected from a total of four. A lever press was reinforced only if the correct object was seen in its corresponding place, and the same object was never reinforced in any of the other three places. Of 430 septal neurons recorded, the responses during the place phase in the four places were significantly different in 58 neurons. Responses of eight of these neurons were also place-differential during the object phase as well as the place phase. Furthermore, when the outside view was not presented before the object phase, differential responses in the object phase disappeared. Responses of 91 neurons in the object phase were differential in terms of go/no-go responses and reward availability. Of these 91 neurons, 72 were further tested on a place-independent asymmetrical go/no-go (AGN) task, which required no conditional discrimination. Forty-three neurons responded differentially only in the PGN task. It is thus concluded that this PGN-specific activity reflected conditional place-object relations. Of the remaining 29 neurons that responded differentially in both tasks, 21 were further tested by a place-independent symmetrical go/no-go task (no-go responses were also rewarded). Responses of 19 of these 21 neurons were related to the reward/nonreward contingency but not to the response contingency. The results suggest that septal nuclei are involved in integrating spatial information, conditional place-object relations, and reward/nonreward contingency.

Animals↗

Localization of dipole by boundary element method in three dimensional reconstructed monkey brain.

The boundary element method was applied to 3-dimensionally reconstructed monkey brain to localize a current source generator (dipole) of somatosensory evoked potentials (SEPs) recorded from epidural electrodes under assumption that a brain is electrically homogeneous and is bounded by a high resistant substance (skull). Absolute mean deviation of estimated dipoles from actual dipoles artificially generated by electrical stimulation at known coordinates in the brain were within 1-3 mm. The estimated dipole computed from SEPs by right median nerve stimulation at latency of P10-N10 waves was located in area 3b of the somatosensory hand area in monkey. Our data suggest that this technique of locating dipoles by the boundary element method applied to a reconstructed brain allows accurate determination of the 3-dimensional coordinates of a dipole.

Algorithms↗

Dipole tracing of monkey somatosensory evoked potentials.

Current source generators (dipoles) of somatosensory evoked potentials (SEPs) in response to electrical stimulation of the median nerve in anesthetized monkeys were localized by the dipole tracing method (DT) which can approximate surface potential distributions to an equivalent dipole. The locations and latencies of dipoles estimated by DT were confirmed by recording multiple unit activities from the parietal cortices of the same monkeys investigated by DT. Loci of generators for each SEP component were: P10 and N10, area 3b; P12, areas 1 and 2; P18, area 5. The results indicate that DT could trace the successive movement of generators of SEPs from the primary somatosensory area to area 5, which has been suggested in neuroanatomical studies to be part of the hierarchical sequence of somatosensory processes.

Animals↗

Monkey hippocampal neuron responses related to spatial and non-spatial influence.

Activity in the monkey hippocampal formation (HF) was analyzed during movement guided by auditory and visual cues. The monkey could control a motorized cab by pressing the proper 1 of 4 available levers within a 2.5 x 2.5 m field. Of 238 HF neurons analyzed, responses of 79 were place related and responses of 110 were task related. Of the task-related neurons, 33 were also place related, and responded to task cues only where place-related responses occurred. The results suggest HF gating of incoming non-spatial information, depending on information about location.

Acoustic Stimulation↗

Rat amygdaloid neuron responses during auditory discrimination.

To investigate amygdaloid contribution to stimulus-affect association and to emotional behavior, single neuron activity was recorded in the basolateral and corticomedial amygdala of the rat amygdala during discrimination of conditioned cue tones associated with positive (glucose and intracranial self-stimulation) and negative (weak electric footshock) unconditioned stimuli. Amygdaloid neurons that responded to two rewarding unconditioned stimuli responded in the same manner to both. Responses to conditioned cue tones and those to rewards were also significantly related, suggesting that amygdaloid neuronal responses to conditioned stimuli are closely related to the affective nature of the corresponding unconditioned stimulation. These might be neuronal functions that underlie stimulus-affect association in the amygdala. In random repeated trials, including acquisition to conditioned cue tones and extinction after acquisition, response plasticity was more evident in basolateral than in corticomedial neurons. Furthermore, more basolateral than corticomedial neurons differentiated glucose and its cue from intracranial self-stimulation and its cue by responding to one but not the other. More basolateral than corticomedial neurons were excited by intracranial self-stimulation and its cue and inhibited by footshock and its cue. The differences between the two nuclear groups suggest that basolateral neurons are more plastic and discriminative, and corticomedial neurons respond indiscriminately to positive and negative unconditioned or conditioned stimuli. The results indicate amygdaloid neuron involvement in stimulus-affect association. Basolateral neurons may be more involved than corticomedial neurons in discriminating and learning conditioned stimuli.

Acoustic Stimulation↗

Neuronal responses in monkey anterior putamen during operant bar-press behavior.

Single neuron activity was recorded in the monkey anterior putamen to compare visuomotor-related responses during operant bar-press behavior with visual discrimination of objects. Of 615 neurons recorded, 9.8% (60/615) responded to the presentation of food during forced delay of access to the bar. Of these 60 neurons, 38 were also tested with nonfood, and 19 of these responded to the nonfood objects regardless of the following movement. The amplitude of the visual-related responses of some differential neurons was graded for different objects to reflect the relative degree of preference for the food presented. However, these responses disappeared in reaction time tasks in which the bar could be accessed for pressing immediately upon presentation of an object. The visual response latency of differential neurons ranged from 50 to 700 ms (mean +/- SD, 386 +/- 211 ms), which was longer than that of the nondifferential responses (207 +/- 204 ms). These results suggest that anterior putamen neurons might participate in estimation of visual information that could be related to forecasting movement.

Animals↗

Monkey hippocampal neurons related to spatial and nonspatial functions.

1. Neural activity in the monkey hippocampal formation (HF) was analyzed during a spatial moving task in which the monkey was guided by auditory and visual cues and when stimuli were presented from various directions. The monkey could control a motorized, movable device (cab) and its route to a target location by pressing the proper one of five available bars in an appropriate sequence (spatial moving task). In any of several locations in the field, neural responses were evident in relation to the presentation of various objects or human movement in some relative direction (left, anterior, right) as a directional stimulus test. 2. Of 238 hippocampal neurons analyzed, 172 (72.3%, 238-66) responded in either the spatial moving task, or to the direction from which stimulation was presented, or to the location of the monkey in the field, or to some combination of these. 3. The activity of 79 (33.2%) neurons was higher when the monkey was in some specific location in the field during the spatial moving task, regardless of the approach route or other task parameters (place related neurons). 4. Responses to the task cues in the spatial moving task were evident in 110 (46.3%) neurons (task related neurons). Of these, 77 (32.4%) neurons were not place related. The remaining 33 (13.9%) neurons were both task related and place related. These neurons responded to task cues in only that part of the field in which place related responses occurred. The neural response to the task cues disappeared when the monkey moved out of the place response region. The place related and task related neural responses disappeared when the room light was switched off. Thus information from the environment outside of the cab contributed to the place related and task related responses. 5. Stimuli presented from certain specific directions induced responses, selectively, in 41 (17.2%) of the neurons (direction related neurons). The dependence of the preferred direction was described in one of three ways--egocentric, allocentric, or place-direction specific. Nineteen egocentric neurons responded to a stimulus only when it was presented from a certain direction relative to the orientation of the monkey, regardless of the location of the monkey. Eleven allocentric neurons responded to a stimulus only when it was presented at a particular position in the room, regardless of the location or orientation of the monkey.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗

Monkey hippocampal neuron responses to complex sensory stimulation during object discrimination.

The purpose of this study was to investigate, during the performance of an object discrimination task, responses of neurons in the monkey hippocampal formation to the sight of several objects that have biological meaning, and compare these responses with those of amygdalar neurons studied previously using the same task. Neuronal activity in the hippocampal formation of conscious monkeys was recorded during performance of a task that led to presentation of familiar rewarding, familiar aversive, or unfamiliar objects. Of 864 neurons recorded in the hippocampal formation and adjacent cortices, 160 (18.5%) responded to the sight of a certain object(s). Responses to the sight of different kinds of objects were analyzed in detail. Nondifferential neurons (n = 73) responded to different objects with no significant difference in response magnitudes, and differential neurons (n = 87) responded to different objects with different response magnitudes. Of the differential neurons, 23 responded more strongly to rewarding objects than to other objects (rewarding-object-dominant neurons), but the magnitude of responses to objects did not necessarily correlates with the order of preferences to the objects as determined from observation of animal behavior. Aversive-object-dominant neurons (n = 13) responded more to aversive objects than to other objects. Unfamiliar-object-dominant neurons (n = 7) responded more to unfamiliar objects than to familiar objects. Selective neurons (n = 10) responded selectively to only one object or one category of objects. Fourteen of the rewarding- or averse-object-dominant neurons were tested in extinction or reversal trials. In 12 of 14 neurons, responses to a rewarding or aversive object did not change, or slightly weakened, in extinction or reversal trials. The results suggest the following. (1) Responses of rewarding- or aversive-object-dominant neurons may be involved in object-reward or object-aversion association. However, responses of many of these neurons might reflect past inputs to reinforcement rather than extant emotional processing. (2) Responses of unfamiliar-object-dominant neurons may be involved in recognition of objects based on their familiar or unfamiliar aspects. These results are further discussed and compared with responsiveness of amygdalar neurons.

Acoustic Stimulation↗

Hippocampal neuronal damage after transient forebrain ischemia in monkeys.

To investigate cerebral injury in the monkey due to transient ischemia, monkeys were each subjected to temporary occlusion of eight (bilateral common carotid, internal and external carotid, and vertebral) major arteries. After 0 (control), 5, 10, 13, 15, and 18 min occlusion, blood flow was restored. The monkeys were sacrificed by perfusion fixation 5 days after the operation, and all brain regions were then histologically examined for ischemic neuronal changes induced by the occlusion. The amplitude of EEG signals from skull and scalp became almost isoelectric within 1-6 min after the onset of occlusion. The EEG signals from the hippocampus were markedly attenuated within 1-4 min, although they did not become completely isoelectric. Blood pressure was significantly increased after 10-min ischemia. Five-min occlusion produced no ischemic neuronal changes except a slight increment of glial cells in the striatum and III, V, and VI layers of the neocortices. After 10- to 15-min occlusion, there were ischemic cell changes restricted exclusively to the CA1 subfield of the hippocampus. Eighteen-min occlusion produced more prominent ischemic neuronal damage in the CA1 subfield of the hippocampus, but ischemic neuronal damage was no longer confined to the hippocampus. These results suggest that only the CA1 subfield of the monkey hippocampus could be damaged by mild ischemic insult. We demonstrate that the limited lesion of the hippocampus, especially the CA1 subfield, after 10- to 15-min occlusion of eight arteries in the monkey, produces a model equivalent to human amnesia caused by transient ischemic insult.

Animals↗

Amino acid and NaCl appetite, and LHA neuron responses of lysine-deficient rat.

Rats' preferences for amino acids and NaCl in their drinking behavior were noted when they were fed either a control diet of gluten plus 20% purified egg protein, or (same rats, different time) a lysine-deficient diet. In control, the order of the rats' preferences was arginine greater than saline greater than monosodium L-glutamate (MSG, umami) greater than glycine greater than water greater than threonine greater than histidine greater than lysine. When fed a lysine-deficient diet the order of preference was lysine greater than saline greater than MSG greater than glycine greater than threonine greater than water greater than arginine greater than histidine. To relate neural activity with preference for amino acids and NaCl, activity of lateral hypothalamic (LHA) neurons was recorded during ingestion of MSG, lysine, arginine, glycine, saline, glucose, or water by the control and lysine-deprived condition, following a different cue tone. When the diet was lysine deficient, some neurons responded specifically to lysine ingestion. More neurons responded nondifferentially during licking in control, and responded to lysine, but fewer to other amino acid ingestion during lysine deficiency. Responses to cue tone were associated with those during licking. The present results suggest that preference for deficient amino acids might be mediated in the LHA.

Amino Acids↗

Parabrachial gustatory neural responses to monosodium glutamate ingested by awake rats.

A sample of 41 gustatory neurons isolated in the parabrachial nuclei of awake, behaving rats was tested with sapid solutions of 0.1 M monosodium glutamate (MSG), 0.5 mM of guanosine 5'-monophosphate (GMP), and a mixture of MSG and GMP as well as with 0.3 M sucrose, 0.1 M NaCl, 0.01 M citric acid, and 0.0001 M QHCl. Interneuronal correlation coefficients and factor analysis indicated that both the sodium cation and glutamic anion contributed to the activity elicited by MSG. Guanosine potentiated the responses to MSG, but only in neurons that also responded to sucrose. These results suggest that the gustatory contribution to the flavor denoted by the Japanese word "umami" may be mediated, in part, by neurons that also respond to chemical described by humans as sweet.

Animals↗

Parabrachial gustatory neural activity during licking by rats.

1. A total of 51 single neurons was recorded from the pontine parabrachial nuclei of three rats being given sapid stimuli either via intraoral infusions or during spontaneous licking behavior. In 46 neurons, sapid stimuli elicited significant taste responses; of these, 28 responded best to NaCl, 15 to sucrose, 2 to citric acid, and 1 to quinine HCl. The remaining five neurons responded significantly only to water. The mean spontaneous rate of taste neurons during the intraoral infusion and licking sessions was 11.1 +/- 1.1 and 10.8 +/- 1.2 (SE) spikes/s, respectively. 2. Of the 39 neurons tested during both licking and intraoral infusions, four responded significantly only to water via either route. The remaining 35 neurons responded significantly to at least some sapid stimuli. The best-stimulus categories remained the same regardless of the route of fluid delivery (24 NaCl best, 10 sucrose best, 1 citric acid best). When the rats were licking the stimuli, nine taste neurons responded significantly to only one sapid chemical [6 Na specific (Ns) and 3 sucrose specific (Ss)] but were more broadly tuned during intraoral infusions. Conversely, three taste neurons that responded specifically during intraoral infusions (3 Na specific) were not as specific when the animal licked the same fluids. 3. Thirty-five taste neurons were tested via both stimulus routes. These data were compared in three ways. First, for each neuron, the responses elicited during licking and intraoral infusions were compared for each of the four standard sapid stimuli. The Pearson correlation coefficients for the 35 taste neurons ranged from 0.9997 to 0.6785, with a mean at 0.953 +/- 0.012 (SE). The second comparison was between stimulus routes across chemicals. With the use of raw responses, the correlation coefficients for NaCl, sucrose, citric acid, and QHCl ranged from 0.925 to 0.778 (t test, P less than 0.0001). With the activity elicited by water subtracted (corrected responses), the correlation coefficients for NaCl, sucrose, citric acid, and QHCl were 0.900, 0.795, 0.369, and 0.211, respectively. The coefficient for QHCl was not significant (t test, P greater than 0.05). Finally, the mean responses to NaCl, sucrose, and citric acid delivered by both routes were compared and found not to differ (paired t test, P greater than 0.05). 4. In separate hierarchical cluster analyses for the licking and infusion data, the largest cluster in each contained all of the Na-best neurons and the next largest, all of the sucrose-best cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗