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H Nishijo

Publications and source records attributed to H Nishijo.

At least 19 recordsLinked to original sources

Neuronal responses to a delayed-response delayed-reward go/nogo task in the monkey posterior insular cortex.

Anatomical connections of the insular cortex suggest its involvement in cognition, emotion, memory, and behavioral manifestation. However, there have been few neurophysiological studies on the insular cortex in primates, in relation to such higher cognitive functions. In the present study, neural activity was recorded from the monkey insular cortex during performance of a delayed-response delayed-reward go/nogo task. In this task, visual stimuli indicating go or nogo responses associated with reward (reward trials) and with no reward (no-reward trials) were presented after eye fixation. In the reward trials, the monkey was required to release a button during presentation of the 2nd visual stimuli after a delay period (delay 1). Then, a juice reward was delivered after another delay (delay 2). The results indicated that the neurons responding in each epoch of the task were topographically localized within the insular cortex, consistent with the previous anatomical studies indicating topographical distributions of afferent inputs from other subcortical and cortical sensory areas. Furthermore, some insular neurons 1) nonspecifically responded to the visual cues and during fixation; 2) responded to the visual cues predicting reward and during the delay period before reward delivery; 3) responded differentially in go/nogo trials during the delay 2; and 4) responded around button manipulation. The observed patterns of insular-neuron responses and the correspondence of their topographical localization to those in previous anatomical studies suggest that the insular cortex is involved in attention- and reward-related functions and might monitor and integrate activities of other brain regions during cognition and behavioral manifestation.

Analysis of Variance↗

Conjunctive effects of reward and behavioral episodes on hippocampal place-differential neurons of rats on a mobile treadmill.

Previous studies reported context (or behavior)-dependent activities of hippocampal place cells, which are suggested to be the neural basis of episodic memory. However, it remains unclear what distinctive items these context-dependent activities encode. We investigated separately the effects of space, locomotion, and episodes with positive/negative reinforcements on activity of place-differential neurons in the hippocampal CA1 area. Rats were placed on a treadmill affixed to a motion stage translocated along a figure 8-shaped track. The track could be navigated by two different routes that shared a common central stem. The stage was paused at the start and end of the routes, where conditioned response tasks with different reinforcements were imposed. As the rats passed the common central stem, some neurons fired differently depending on the route. Comparison of hippocampal spatial firing patterns across different conditions with and without treadmill operation and/or the tasks indicated that these route-dependent spatial firing patterns were sensitive to locomotion, the tasks, and vestibular sensation or visual cues such as optic flow. The results suggest that external sensory inputs, path integration, and reinforcement context are all integrated in the hippocampus, which might provide the neural basis of episodic memory.

Animals↗

Unambiguous representation of overlapping serial events in the rat hippocampal formation.

The hippocampal formation is suggested to be crucial in unambiguous representation of overlapping temporal sequences in episodic memory. We hypothesized that, if this was true, the hippocampal formation neurons would differentially respond to the same elements even in different temporal sequences. The present study was designed to investigate hippocampal formation CA1 neuronal activity of rats during performance of a conditional delayed stimulus-response association task in which three stimuli were conditionally and serially presented with a delay. In the task, the pairs of the second and third stimuli were overlapped across the trials, but separated by the preceding first stimuli. Conditioned tones coming from one of three possible directions were followed, after a short delay, by one of three pairs of reinforcement series. The pairs consisted of air puff (aversive sensory stimuli) and tube protrusion (which allowed licking sucrose behavior) in the following combinations: air puff-tube protrusion, tube protrusion-tube protrusion and tube protrusion-air puff. The pairs were interposed by a 2 s delay. The three conditioned tone directions were associated with these three pairs in a one-to-one correspondence, and its association was conditional to three possible conditioned tone frequencies (300, 530, and 1,200 Hz). The responses of 107 neurons to the air puff and tube protrusion were analyzed by two-way ANOVA (task condition x reinforcement situation). Of 42 air puff-responsive and 64 tube protrusion-responsive neurons, 36 and 53 displayed significant main effects and/or significant interaction, respectively. Furthermore, neural responses during the delay periods were dependent on the task conditions. The results indicated that the majority of the hippocampal formation neurons showed task condition- and/or reinforcement situation-dependent responses, suggesting a crucial role of the hippocampal formation in representation of overlapping serial events in episodic memory.

Action Potentials↗

Contribution of hippocampal place cell activity to learning and formation of goal-directed navigation in rats.

Although extensive behavioral studies have demonstrated that hippocampal lesions impair navigation toward specific places, the role of hippocampal neuronal activity in the development of efficient navigation during place learning remains unknown. The aim of the present study was to investigate how hippocampal neuronal activity changes as rats learn to navigate efficiently to acquire rewards in an open field. Rats were pre-trained in a random reward task where intracranial self-stimulation rewards were provided at random locations. Then, the rats were trained in a novel place task where they were rewarded at two specific locations as they repeatedly shuttled between them. Hippocampal neuronal activity was recorded during the course of learning of the place task. The rats learned reward sites within several sessions, and gradually developed efficient navigation strategies throughout the learning sessions. Some hippocampal neurons gradually changed spatial firing as the learning proceeded, and discharged robustly near the reward sites when efficient navigation was established. Over the learning sessions, the neuronal activity was highly correlated to formation of efficient shuttling trajectories between the reward sites. At the end of the experiment, spatial firing patterns of the hippocampal neurons were re-examined in the random reward task. The specific spatial firing patterns of the neurons were preserved if the rats navigated, as if they expected to find rewards at the previously valid locations. However, those specific spatial firing patterns were not observed in rats pursuing random trajectories. These results suggest that hippocampal neurons have a crucial role in formation of an efficient navigation.

Action Potentials↗

Differential activation in the medial temporal lobe during a sound-sequence discrimination task across age in human subjects.

To elucidate the brain mechanisms to encode sequential events, event-related potentials (ERPs) were recorded during a sound-sequence discrimination task using young and middle-aged adult subjects. In the task, a series of six or 12 kinds of natural sounds were sequentially presented; 70-80% of the stimuli were presented in a fixed order (Non-target), but the remaining stimuli, in a random order (Target). The subjects were instructed to detect the Targets and press a button at the end of each Target. In a control task, the same sounds were randomly presented (Control), and they were instructed to press the button at the end of each sound. Behavioral results indicated that the young subjects learned the task faster than did the middle-aged subjects. Positive ERP waves were evoked by Targets and Non-targets in the parieto-occipital area around 300-700 ms after stimulus onset. The mean amplitudes during this period in the young subjects were larger in Target than Control conditions, and those in Target condition were larger in the young than middle-aged subjects. Furthermore, the mean amplitudes in the Target condition were significantly correlated with behavioral performance. Equivalent dipoles for the ERPs evoked by Targets were estimated in the medial temporal lobe including the hippocampal formation and parahippocampal gyrus. The results suggest that the ERPs around 300-700 ms latency are involved in sound-sequence information processing. Furthermore, decrease in amplitudes of this positivity in the middle-aged subjects suggests that age-related memory decline is associated with deficits in encoding and retrieval of unfamiliar sequence.

Acoustic Stimulation↗

Light and electron microscopic study of cholinergic and noradrenergic elements in the basolateral nucleus of the rat amygdala: evidence for interactions between the two systems.

Pharmacological studies have suggested that the cholinergic (ACh) and noradrenergic (NA) systems in the amygdala (AM) play an important role in learning and memory storage and that the two systems interact to modulate memory storage. To obtain anatomical evidence for the interaction, the organization of the ACh and NA fibers in rat AM was investigated by immunocytochemistry for choline acetyltransferase (ChAT) and dopamine-beta-hydroxylase (DBH) in conjunction with light, confocal laser scanning, and electron microscopy (LM, CLSM, and TEM, respectively). LM showed that the ChAT immunoreactivity was densest in the basolateral nucleus (BL), whereas the DBH immunoreactivity was densest in the posterior BL. CLSM demonstrated that the ChAT-immunoreactive profiles in the BL were frequently located in juxtaposition to the DBH-immunoreactive axons. The TEM observations were as follows: The majority of the synapses formed by ChAT-immunoreactive terminals were symmetric, but DBH-immunoreactive axons formed both asymmetric and symmetric synapses. The ChAT-immunoreactive terminals usually established the symmetric synaptic contacts with the DBH-immunoreactive terminals and varicosities. The DBH-immunoreactive terminals formed the asymmetric synapses with the ChAT-immunoreactive dendrites of the intrinsic neurons within the AM. The results provide anatomical substrates for mnemonic functions of the ACh and NA systems and for the interactions between the two systems in the AM.

Amygdala↗

Retrospective and prospective coding for predicted reward in the sensory thalamus.

Reward is important for shaping goal-directed behaviour. After stimulus-reward associative learning, an organism can assess the motivational value of the incoming stimuli on the basis of past experience (retrospective processing), and predict forthcoming rewarding events (prospective processing). The traditional role of the sensory thalamus is to relay current sensory information to cortex. Here we find that non-primary thalamic neurons respond to reward-related events in two ways. The early, phasic responses occurred shortly after the onset of the stimuli and depended on the sensory modality. Their magnitudes resisted extinction and correlated with the learning experience. The late responses gradually increased during the cue and delay periods, and peaked just before delivery of the reward. These responses were independent of sensory modality and were modulated by the value and timing of the reward. These observations provide new evidence that single thalamic neurons can code for the acquired significance of sensory stimuli in the early responses (retrospective coding) and predict upcoming reward value in the late responses (prospective coding).

Animals↗

Electroencephalogram spectral characteristics after alcohol ingestion in Japanese men with aldehyde dehydrogenase-2 genetic variations: comparison with peripheral changes.

BACKGROUND: Electroencephalographic (EEG) activity induced by alcohol ingestion may be influenced by individual differences in alcohol metabolism. Specifically, an absence of the low Km isozyme of aldehyde dehydrogenase (ALDH), found in many Asians, may be related to alterations of EEGs. METHODS: EEG power spectral changes induced by 0.4 ml/kg of alcohol ingestion were compared in two groups of Japanese subjects: NN (ALDH2*1/1, n = 19) and ND (ALDH2*2/1, n = 12). Peripheral changes in heart rate and facial skin temperature were evaluated after the same treatment. Blood ethanol, acetaldehyde, and catecholamine levels were determined to evaluate mediation of the ethanol metabolite, acetaldehyde, and its indirect action on EEGs through the effects on peripheral systems. RESULTS: As expected, blood acetaldehyde was about 10-fold higher in the ND subjects compared with the NN subjects during the postingestion period. Ethanol produced characteristic EEG changes during and after ingestion. The ND subjects, however, displayed brief periods of decrease in slow alpha immediately after alcohol ingestion and showed no long-term EEG changes. The EEG changes were parallel to peripheral changes. CONCLUSIONS: The lack of increased EEG power in the ND subjects may be partly mediated by a direct action of the high concentration of acetaldehyde in the central nervous system that penetrates from the peripheral blood. In addition to this direct action of acetaldehyde, an indirect action, such as feedback from peripheral changes, might prevent the characteristic increase in alpha and beta power observed in the NN subjects.

Acetaldehyde↗

Ameliorative effects of tamolarizine on place learning impairment induced by transient forebrain ischemia in rats.

In the present study we investigated the effect of (+/-)-1-(3, 4-dimethoxyphenyl)-2-(4-diphenylmethylpiperazinyl) ethanol dihydrochloride (tamolarizine), a calcium entry blocker, on place learning impairment in rats with damage selective to the hippocampal CA1 subfield induced by transient forebrain ischemia. Tamolarizine was administered (40 mg/kg) immediately after 15-min brain ischemia. Place learning was tested in a task in which the rat was required to alternatively visit two places located diametrically opposite each other in an open field. The ischemia+saline group showed severe learning impairment in this task; their performance level was significantly inferior to that of the sham-operated group through the test period (30 days). Although the ischemia+tamolarizine group showed slight impairment of place learning during the course of this test, they later reached almost the same performance level as the sham-operated group. Selective neuronal loss in the CA1 subfield was much less in the ischemia+tamolarizine group than in the ischemia+saline group. These results indicate that tamolarizine treatment protects the hippocampus from ischemic brain damage and ameliorates place learning impairment.

Animals↗

Functional role of the limbic system and basal ganglia in motivated behaviors.

It has been suggested that the cortico- and limbic-striatal systems are important in various motor functions such as motivated behaviors. In this paper we review our previous studies to investigate neuronal mechanisms of feeding behaviors. We recorded neuronal activity from the amygdala, caudate nucleus, globus pallidus, and substantia nigra during feeding behavior in monkeys, and compared neuronal responses recorded from these brain areas. First, of 710 amygdalar neurons tested, 129 (18.2%) responded to single sensory stimulation (48 to vision, 32 to audition, 49 to ingestion), 142 (20%) to multimodal stimulation, and 20 to only one item with affective significance. Eight food related amygdalar neurons were tested in reversal by salting food or introducing saline, and all responses were modulated by reversal. These results suggest that the amygdala might be important in ongoing recognition of the affective significance of complex stimuli (food-nonfood discrimination). Second, activity was recorded from 351 neurons in the head of the caudate nucleus of monkeys during an operant feeding task. The 16% of these neurons responded in the discrimination phase. Some of these neurons responded specifically to food. The magnitude of these food-specific neurons depended on the rewarding nature of the food (reward value), and was inversely related to the latency of the onset of bar press. Of the caudate neurons, 10% responded in the bar press phase. Activity of most neurons which responded in the bar press phase was not correlated to individual bar presses. Cooling of the dorsolateral prefrontal cortex abolished sustained responses during bar pressing, but did not abolish the feeding behavior. However, bar press speed tended to be delayed by prefrontal cooling. Third, activity of 358 neurons was recorded from the monkey globus pallidus, and 204 neurons responded during the feeding task. In the globus pallidus, few neurons responded to food in the discrimination phase. On the other hand, activity of most responsive neurons changed during bar press and/or ingestion phases. Activity of about half of these responsive neurons was directly related to specific feeding motor acts such as arm extension, flexion, bar pressing, grasping, chewing, etc. Some of these neurons showed motor-related responses with gradual and preparatory responses. These motor-related neurons were located mainly in the caudodorsal part of the globus pallidus. On the other hand, about one third, especially in the rostroventral part of the globus pallidus, showed dissociating responses in that they responded during bar pressing for food or during ingestion in an operant task, but not during bar pressing for nonfood or during forcible ingestion. The response magnitude of the neurons during arm extension and bar pressing depended on the nature of the food. Fourth, activity of 261 neurons was recorded from the substantia nigra pars reticulata. Most of responding neurons (more than two-thirds of the recorded neurons) responded during the bar press and/or ingestion phases. Activity of the one-third of neurons was related to specific motor execution such as arm extension, flexion and bar pressing, but not to motor preparation. These neurons were located mainly in the rostral part of the nucleus. More than one-third of the recorded neurons responded during feeding and/or drinking acts and intra- and perioral sensory stimuli, and were located mainly in the caudomedial part of the nucleus. Based upon these responses and known anatomical evidence, various information including that from the amygdala and prefrontal cortex is integrated in the basal ganglia, and converted to coordinated motivated behaviors such as feeding behavior.

Animals↗

Orbital cortex neuronal responses during an odor-based conditioned associative task in rats.

Neuronal activity in the rat orbital cortex during discrimination of various odors [five volatile organic compounds (acetophenone, isoamyl acetate, cyclohexanone, p-cymene and 1,8-cineole), and food- and cosmetic-related odorants (black pepper, cheese, rose and perfume)] and other conditioned sensory stimuli (tones, light and air puff) was recorded and compared with behavioral responses to the same odors (black pepper, cheese, rose and perfume). In a neurophysiological study, the rats were trained to lick a spout that protruded close to its mouth to obtain sucrose or intracranial self-stimulation reward after presentation of conditioned stimuli. Of 150 orbital cortex neurons recorded during the task, 65 responded to one or more types of sensory stimuli. Of these, 73.8% (48/65) responded during presentation of an odor. Although the mean breadth of responsiveness (entropy) of the olfactory neurons based on the responses to five volatile organic compounds and air (control) was rather high (0.795), these stimuli were well discriminated in an odor space resulting from multidimensional scaling using Pearson's correlation coefficients between the stimuli. In a behavioral study, a rat was housed in an equilateral octagonal cage, with free access to food and choice among eight levers, four of which elicited only water (no odor, controls), and four of which elicited both water and one of four odors (black pepper, cheese, rose or perfume). Lever presses for each odor and control were counted. Distributions of these five stimuli (four odors and air) in an odor space derived from the multidimensional scaling using Pearson's correlation coefficients based on behavioral responses were very similar to those based on neuronal responses to the same five stimuli. Furthermore, Pearson's correlation coefficients between the same five stimuli based on the neuronal responses and those based on behavioral responses were significantly correlated. The results demonstrated a pivotal role of the rat orbital cortex in olfactory sensory processing and suggest that the orbital cortex is important in the manifestation of various motivated behaviors of the animals, including odor-guided motivational behaviors (odor preference).

Animal Feed↗

Effects of chronic stress on hypothalamic lnterleukin-1beta, interleukin-2, and gonadotrophin-releasing hormone gene expression in ovariectomized rats.

The influence of chronic stress on the expression of interleukin (IL)-1beta and IL-2 mRNAs in ovariectomized rat brains, and the physiological consequences of the expression of these cytokines on hypothalamic-pituitary-gonadal (HPG) activity were investigated. Using polymerase chain reaction (PCR)-assisted semiquantitative analysis, we demonstrated alterated expression of IL-1beta and IL-2 mRNA during repeated cold stress; the expression of both IL-beta and IL-2 mRNA increased in the medial preoptic area and ventromedial hypothalamus, and decreased in the lateral hypothalamic area. In the arcuate nucleus/median eminence, IL-2 mRNA expression was dramatically decreased, in contrast to the increase in IL-1beta mRNA expression. Concomitant analysis of GnRH mRNA expression indicated significant suppression of GnRH synthesis in the chronic phase, and a strong negative correlation with cytokine expression in the medial preoptic area. Similar results were obtained in intact females exposed to this stress. These results, together with previous pharmacological studies, suggest that chronic stress may induce reproductive dysfunction through the effects of stress-induced expression of endogenous cytokines.

Animals↗

Hypothalamic and amygdalar neuronal responses to various tastant solutions during ingestive behavior in rats.

The forebrain, including the amygdala (AM) and hypothalamus, may be a higher brain center that modulates the activity of a brainstem neural system that influences ingestive behavior via descending projections. In this study, to elucidate the characteristics of sensory information processing in the forebrain in relation to this putative connection, we recorded neuronal activity in the AM and hypothalamus [lateral hypothalamic area (LHA), medial hypothalamic area (MHA)] of rats during discrimination of conditioned sensory stimuli and the ingestion of various tastant solutions. Of 420 responsive AM neurons identified, 24 were taste responsive and located mainly in the central nucleus of the AM. Multivariate analyses of these taste neurons suggested that in the AM, taste quality is processed on the basis of palatability. In the hypothalamus, of 282 LHA and MHA neurons recorded, 144 responded to one or more conditioned auditory stimuli and/or licking of one or more solutions. Stress, which is known to influence feeding behavior, increased the mean spontaneous activity of LHA neurons but decreased the mean spontaneous neuronal activity of MHA neurons. This pattern of changes in spontaneous neuronal activity correlated with alterations in feeding behavior during stress. Furthermore, the activity of both AM and LHA neurons was modulated flexibly during conditioned associative learning. Together, the data suggest that the activity of the AM and hypothalamic neurons is altered when animals must modulate ingestive behavior by learning a new stimulus associated with food and by being exposed to stress, suggesting that these forebrain areas are important modulators of the activity of a basic neural system in the brainstem that influences ingestive behavior.

Acoustic Stimulation↗

Effects of repeated cold stress on activity of hypothalamic neurons in rats during performance of operant licking task.

The present study investigated the effects of repeated cold stress on single neuron activity in the lateral hypothalamic area (LHA) and medial hypothalamic area (MHA) of behaving rats. The rats were trained to lick a protruding spout in response to one of several cue-tone stimuli (CTSs) to ingest water, or amino acid, NaCl or glucose solution. Following this training, the rats were raised under either stressed (repeated temperature changes between -3 and 24 degrees C) or control (24 degrees C) condition for 2 mo. During this period, neuronal activity was recorded in the LHA and MHA. For rats raised under the stressed condition, mean spontaneous firing rate of LHA neurons was significantly greater than for rats under the control condition. More LHA neurons in the stressed rats responded, with an accompanying decrease in activity (inhibitory response), to CTSs than in the control rats. During extinction learning, some LHA neurons enhanced or reversed the responses to CTSs in the stressed rats, whereas no LHA neurons showed such response changes in the control rats. In contrast to the effects of the stressed condition on LHA neuron activity, mean spontaneous firing rate of MHA neurons in the stressed rats was significantly smaller than in the control rats. Fewer MHA neurons in the stressed rats responded to CTSs and/or ingestion of sapid solutions. The preceding results suggested that repeated cold stress produces a specific pattern of changes in spontaneous activity and responses to sensory stimuli in LHA and MHA neurons; this could underlie the behavioral changes induced by repeated cold stress such as hyperphagia and hyper-reactivity to sensory stimuli.

Acoustic Stimulation↗

A combined electrophysiological and video data acquisition system using a single computer.

Numerous experimental paradigms in behavioral electrophysiology and neuroethology require simultaneous recording of neural signals and behavior. A computer fitted with an analog to digital converter and a frame grabber was configured to perform both tasks. The analog to digital converter collected electrophysiological data while the frame grabber recorded video images. Since spike and image information were present in one computer, arbitrary combinations of electrophysiological and behavioral parameters could be used as the basis of an operant conditioning paradigm. The system was used to record subicular cell firing in rats performing a place search task. The computer monitored the output of the analog to digital converter for supra-threshold events. When one was detected, a block of samples (pre- and post-trigger) was stored in memory. The same computer also scanned every video frame to find the rat, and recorded a image of its behavior. The location of the rat was then quickly calculated. If it satisfied the task conditions, a brain reward pathway (medial forebrain bundle) was stimulated. The recording of neural and image data was monitored in real-time by writing spike waveforms and location data directly to video card RAM.

Algorithms↗

Spatial- and task-dependent neuronal responses during real and virtual translocation in the monkey hippocampal formation.

Neuropsychological data in humans demonstrated a pivotal role of the medial temporal lobe, including the hippocampal formation (HF) and the parahippocampal gyrus (PH), in allocentric (environment-centered) spatial learning and memory. In the present study, the functional significance of the monkey HF and PH neurons in allocentric spatial processing was analyzed during performance of the spatial tasks. In the tasks, the monkey either freely moved to one of four reward areas in the experimental field by driving a cab that the monkey rode (real translocation task) or freely moved a pointer to one of four reward areas on the monitor (virtual translocation task) by manipulating a joystick. Of 389 neurons recorded from the monkey HF and PH, 166 had place fields that displayed increased activity in a specific area in the experimental field and/or on the monitor (location-differential neurons). More HF and PH neurons responded in the real translocation task. These neurons had low mean spontaneous firing rates (0.96 spikes/sec), similar to those of rodent HF place cells. The remaining nonresponsive neurons had significantly higher mean firing rates (8. 39 spikes/sec), similar to interneurons or theta cells in the rodent HF. Furthermore, most location-differential neurons showed different responses in different tasks. These results suggest that the HF and PH are crucial in allocentric information processing and, moreover, that the HF can encode different reference frames that are context or task-dependent. This may be the neural basis of episodic memory.

Animals↗

Active spatial information processing in the septo-hippocampal system.

The hippocampal formation (HF) receives the final outputs from all association cortices, and processes and integrates this diverse information. Our neurophysiological data in rats and monkeys suggest active selection of relevant sensory information in the HF. In an open field, rat HF neurons strengthened their sensitivity to more relevant variables among various movement variables such as movement speed, direction, and turning angle based on navigation contexts. The HF place-related activity in the monkey, which rode on a movable cab, became obscure in passive translocation of a monkey by an experimenter. This suggests that the animal actively senses the environment surrounding it during spatial navigation, and that spatial correlates of HF neurons depend on this active sensing. In the monkey septal nuclei that receive hippocampal outputs, some neurons were differential to specific views from 4 specific locations in an experimental room (place-differential responses). Multidimensional scaling (MDS) analysis of place-differential responses indicated that the 4 locations represented in a 2-dimensional virtual space at relative positions were similar to those in the real experimental room. This might be a neurophysiological basis of a cognitive map and path finding. These results are consistent with recent human PET studies that indicated HF involvement in recalling routes and landmarks. Thus, a cognitive mapping system represented in the HF plays a pivotal role in active computation for path finding.

Animals↗

Emotional and behavioral correlates of the anterior cingulate cortex during associative learning in rats.

Neuronal activity was recorded from the anterior cingulate cortex of behaving rats during discrimination and learning of conditioned stimuli associated with or without reinforcements. The rats were trained to lick a protruding spout just after a conditioned stimulus to obtain reward (intracranial self-stimulation or sucrose solution) or to avoid aversion. The conditioned stimuli included both elemental (auditory or visual stimuli) and configural (simultaneous presentation of auditory and visual stimuli predicting reward outcome opposite to that predicted by each stimulus presented alone) stimuli. Of the 62 anterior cingulate neurons responding during the task, 38 and four responded differentially and non-differentially to the conditioned stimuli (conditioned stimulus-related neurons), respectively. Of the 38 differential conditioned stimulus-related neurons, 33 displayed excitatory (n = 10) and inhibitory (n = 23) responses selectively to the conditioned stimuli predicting reward. These excitatory and inhibitory differential conditioned stimulus-related neurons were located mainly in the cingulate cortex areas 1 and 3 of the rostral and ventral parts of the anterior cingulate cortex, respectively. The remaining 20 neurons responded mainly during intracranial self-stimulation and/or ingestion of sucrose (ingestion/intracranial self-stimulation-related neurons). Increase in activity of the ingestion/intracranial self-stimulation-related neurons was correlated to the first lick to obtain rewards during the task, suggesting that the activity reflected some aspects of motor functions for learned instrumental behaviors. These ingestion/intracranial self-stimulation-related neurons were located sparsely in cingulate cortex area 1 of the rostral part of the anterior cingulate cortex and densely in frontal area 2 of the caudal and dorsal parts of the anterior cingulate cortex. Analysis by the multidimensional scaling of responses of 38 differential conditioned stimulus-related neurons indicated that the anterior cingulate cortex categorized the conditioned stimuli into three groups based on reward contingency, regardless of the physical characteristics of the stimuli, in a two-dimensional space; the three conditioned (two elemental and one configural) stimuli predicting sucrose solution, the three conditioned (two elemental and one configural) stimuli predicting no reward, and the lone conditioned stimulus predicting intracranial self-stimulation. The results suggest that the anterior cingulate cortex is organized topographically; stimulus attributes predicting reward or no reward are represented in the rostral and ventral parts of the anterior cingulate cortex, while the caudal and dorsal parts of the anterior cingulate cortex are related to execution of learned instrumental behaviors. These results are in line with recent neuropsychological studies suggesting that the rostral part of the anterior cingulate cortex plays a crucial role in socio-emotional behaviors by assigning a positive or negative value to future outcomes.

Acoustic Stimulation↗