Modifications of reward expectation-related neuronal activity during learning in primate striatum

This study investigated neuronal activity in the anterior striatum while monkeys repeatedly learned to associate new instruction stimuli with known behavioral reactions and reinforcers. In a delayed go-nogo task with several trial types, an initial picture instructed the animal to execute or withhold a reaching movement and to expect a liquid reward or not. During learning, new instruction pictures were presented, and animals guessed and performed one of the trial types according to a trial-and-error strategy. Learning of a large number of pictures resulted in a learning set in which learning took place in a few trials and correct performance exceeded 80% in the first 60-90 trials. About 200 task-related striatal neurons studied in both familiar and learning conditions showed three forms of changes during learning. Activations related to the preparation and execution of behavioral reactions and the expectation of reward were maintained in many neurons but occurred in inappropriate trial types when behavioral errors were made. The activations became appropriate for individual trial types when the animals' behavior adapted to the new task contingencies. In particular, reward expectation-related activations occurred initially in both rewarded and unrewarded movement trials and became subsequently restricted to rewarded trials. These changes occurred in parallel with the visible adaptation of reward expectations by the animals. The second learning change consisted in decreases of task-related activations that were either restricted to the initial trials of new learning problems or persisted during the subsequent consolidation phase. They probably reflected reductions in the expectation and preparation of upcoming task events, including reward. The third learning change consisted in transient or sustained increases of activations. These might reflect the increased attention accompanying learning and serve to induce synaptic changes underlying the behavioral adaptations. Both decreases and increases often induced changes in the trial selective occurrence of activations. In conclusion, neurons in anterior striatum showed changes related to adaptations or reductions of expectations in new task situations and displayed activations that might serve to induce structural changes during learning.     

Influence of expectation of task duration on efficiency of muscular activity.

Tested the hypothesis that intensity and organization of muscular activity is a function of s's expectation of a task's duration. The electrical activities of the following muscles were measured while 10 male undergraduates and instructors were holding a 19-lb weight under expectation for short and long tasks: biceps brachii, brachioradials, brachialis, and flexor carpi ulnaris. For the intervals measured, there was less electrical activity in all muscles during the long task. The less appropriate muscle showed the largest relative decrease. Results are interpreted as evidence of superior organization of activity under expectation of a task of long duration of work over expectation of a short duration of work. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Influence and reward in structured two-person interactions.

8 pairs of Ss were run in each of 4 different dyadic reward systems using a continuous response task. The 2 Ss within each pair were made interdependent in their rewards by imposing a functional relationship between the responses made by one S and the outcomes delivered to the other S, and vice versa. Each pair was given 100 consecutive trials. 3 influence responses were appended to the task for 4 of the 8 pairs in each reward system. These appended responses permitted an S to communicate a request to the other S concerning the latter's continuous response on the next trial. Results from systems with no communication confirm the predictions of reward stability based on a stochastic model. Without communication, 1 of the 4 systems stabilize; with communication, 2 systems stabilize. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavior-related activity of primate dopamine neurons

In view of the behavioral deficits arising after lesions of midbrain dopamine systems, we recorded single dopamine neuron activity in monkeys which learned and performed reaction time tasks, delayed response tasks, and controlled, self-initiated movements. Dopamine neurons respond in a rather homogeneous fashion to salient external stimuli that attract the attention of the subject. Depending on the particular behavioral situation, dopamine neurons are activated by primary liquid and food rewards during learning or in the absence of predictive stimuli, by conditioned stimuli predicting reward and eliciting behavioral reactions, and by novel, unexpected stimuli. Thus, dopamine neurons signal the presence of reward-related, alerting stimuli that need to be processed by the subject with high priority. Besides these phasic responses, dopamine systems apparently operate also in a tonic mode, as inferred from the beneficial effects of dopamine receptor agonist drugs on Parkinsonian symptoms. Whereas the phasic responses may mediate alerting functions or possibly reward-directed learning, the tonic activity may be involved in maintaining states of behavioral alertness and thus enable-movements and cognitive processes. These data provide neurophysiological correlates for the involvement of dopamine neurons in central processes determining the behavioral reactivity of the subject to important environmental events, and possibly the learning of reward-directed behavior.     

Characteristics of basolateral amygdala neuronal firing on a spatial memory task involving differential reward.

Previous research has shown that spatial, movement, and reward information is integrated within the ventral striatum (VS). The present study examined the possible contribution of the basolateral nuclei of the amygdala (BLA) to this interaction by examining behavioral correlates of BLA neurons while rats performed multiple memory trials on an 8-arm radial maze. Alternate arms consistently held 1 of 2 different amounts of reward. Recorded cells were correlated with motion, auditory input, space, and reward acquisition. Reward-related units were found that anticipated reward encounter, that responded during reward consumption, and that differentiated between high and low reward magnitude. This is consistent with the hypothesis that BLA neurons may provide the VS with reward-related information that could then be integrated with spatial information to ultimately affect goal-directed behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bcl-2 protein as a marker of neuronal immaturity in postnatal primate brain

The distribution of neurons expressing immunoreactivity for the protein Bcl-2 was studied in the brain of squirrel monkeys (Saimiri sciureus) of various ages. Several subsets of small and intensely immunoreactive neurons displaying an immature appearance were disclosed in the amygdala and piriform cortex. The piriform cortex exhibited clusters of various forms in which Bcl-2+ neurons appeared linked to one another by their own neurites. The subventricular zone, which is known to harbor the largest population of rapidly and constitutively proliferating cells in the adult rat brain, was intensely stained, particularly at the basis of the lateral ventricle. A long and dorsoventrally oriented Bcl-2+ fiber fascicle was seen to emerge from the subventricular zone, together with numerous Bcl-2+ cells that formed a densely packed column directed at the olfactory tubercle. In adult and aged monkeys, the small and intensely labeled neurons were progressively replaced by larger and more weakly stained neurons in the amygdala and piriform cortex. In contrast, Bcl-2 immunostaining did not change with age in the subventricular zone and olfactory tubercle, the islands of Calleja of which were markedly enriched with Bcl-2. The dentate gyrus contained only a few layers of intensely labeled granule cells in juvenile monkeys, but the number of these layers increased markedly in adult and aged monkeys. These findings suggest that Bcl-2 can serve as a marker of both proliferating and differentiating neurons and indicate that such immature neurons may be much more widespread than previously thought in postnatal primate brain.     

Mnemonic neuronal activity in somatosensory cortex

Single-unit activity was recorded from the hand areas of the somatosensory cortex of monkeys trained to perform a haptic delayed matching to sample task with objects of identical dimensions but different surface features. During the memory retention period of the task (delay), many units showed sustained firing frequency change, either excitation or inhibition. In some cases, firing during that period was significantly higher after one sample object than after another. These observations indicate the participation of somatosensory neurons not only in the perception but in the short-term memory of tactile stimuli. Neurons most directly implicated in tactile memory are (i) those with object-selective delay activity, (ii) those with nondifferential delay activity but without activity related to preparation for movement, and (iii) those with delay activity in the haptic-haptic delayed matching task but no such activity in a control visuo-haptic delayed matching task. The results indicate that cells in early stages of cortical somatosensory processing participate in haptic short-term memory.     

Emergence of spatio-temporal patterns in neuronal activity

This paper explores if dynamic modulation of coherent firing serves cortical functions. We recorded neuronal activity in the frontal cortex of behaving monkeys and found that temporal coincidences of spikes firing of different neurons can emerge within a fraction of a second in relation to the animal behavior. The temporal patterns of the correlation could not be predicted from the modulations of the neurons firing rate and finally, the patterns of correlation depend on the distance between neurons. These findings call for a revision of prevailing models of neural coding that solely rely on firing rates. The findings suggest that modification of neuronal interactions can serve as a mechanism by which neurons associate rapidly into a functional group in order to perform a specific computational task. Increased correlation between members of the groups, and decreased or negative correlation with others, enhance the ability to dissociate one group from concurrently activated competing groups. Such modulation of neuronal interactions allows each neuron to become a member of several different groups and participate in different computational tasks.     

Reduced activity of the pyruvate dehydrogenase complex but not cytochrome c oxidase is associated with neuronal loss in the striatum following short-term forebrain ischemia

Infections are a major cause of morbidity and mortality among immunocompromised patients. This report discusses bacterial and mycotic infections prophylaxis in the granulocytopenic patients with hematologic malignancies. Various strategies have been derived to prevent the infections: a combination of oral antibacterial and antifungal prophylaxis with quinolones and newer azoles (fluconazole, itraconazole), high efficiency particulate air filtration, protective isolation and management of central venous catheter. However, the emergence of antibiotic resistant organism continues to pose a major challenge to the successful eradication and prevention of infections in neutropenic host, and demands the development of innovative approaches to antibiotic use and infection control procedures.     

Influence of predictive information on responses of tonically active neurons in the monkey striatum

Influence of predictive information on responses of tonically active neurons in the monkey striatum. J. Neurophysiol. 80: 3341-3344, 1998. We investigated how the expectation of a signal of behavioral significance influences the activity of tonically active neurons in the striatum of two monkeys performing a simple reaction time task under two conditions, an uncued condition in which the trigger stimulus occurred randomly in time and a cued condition in which the same trigger was preceded by an instruction stimulus serving as a predictive signal for the forthcoming signal eliciting an immediate behavioral reaction. Both monkeys benefited from the presence of the instruction stimulus to reduce their reaction time, suggesting an increased ability to predict the trigger onset during cued trials compared with uncued trials. A majority of neurons (199/272, 73%) showed a phasic reduction in activity after the onset of the trigger stimulus in the uncued condition, whereas only 38% responded to the same stimulus when it was preceded by the instruction. Furthermore, magnitudes of trigger responses in the uncued condition were significantly higher than in the cued condition. Fifty-seven percent of the neurons responded to the instruction stimulus, and one-half of the neurons losing their response to the trigger in the cued condition responded to the instruction stimulus. These findings suggest that responses of tonic striatal neurons to a trigger stimulus for movement were influenced by predictive information.     

Local regulation of primate granulosa cell aromatase activity

Granulosa cells produce inhibin and activin, proteins implicated in the local regulation of preovulatory follicular development. To assess interactions among FSH, LH, inhibin and activin on primate granulosa cell aromatase activity, we studied primary granulosa cell cultures from the ovaries of the common marmoset (Callithrix jacchus), a monkey with an ovarian cycle similar in length to the human cycle. The distinctive action of activin was augmentation of gonadotropin-responsive aromatase activity throughout antral follicular development. FSH-stimulated aromatase activity in granulosa cells from immature follicles was augmented many fold by picomolar amounts of activin. In cell cultures from preovulatory follicles, the presence of activin stimulated basal aromatase activity in the absence of gonadotropin, as well as augmenting the action of LH. Thus, locally produced activin has the potential to modulate aromatase activity in developing ovarian follicles. By contrast, inhibin or inhibin alpha-subunit purified from bovine follicular fluid had minimal effects on aromatase activity. The only significant effect was slight suppression of FSH-inducible aromatase activity in granulosa cells from immature follicles at an inhibin concentration of 100 ng/ml. The finding that inhibin has a negligible effect on aromatase activity in granulosa cells from mature follicles suggests that it is unlikely to exert a physiologically significant influence on aromatase activity in vivo. However, evidence from other studies suggests that inhibin might affect aromatization indirectly through acting locally to modulate thecal androgen (aromatase substate) production. Therefore, both inhibin and activin have the potential to contribute at different levels to paracrine and autocrine regulation of follicular oestrogen synthesis.     

Olfactory neuronal responses in the primate orbitofrontal cortex: analysis in an olfactory discrimination task

1. The primate orbitofrontal cortex receives inputs from the primary olfactory (pyriform) cortex and also from the primary taste cortex. To investigate how olfactory information is encoded in the orbitofrontal cortex, the responses of single neurons in the orbitofrontal cortex and surrounding areas were recorded during the performance of an olfactory discrimination task. In the task, the delivery of one of eight different odors indicated that the monkey could lick to obtain a taste of sucrose. If one of two other odors was delivered from the olfactometer, the monkey had to refrain from licking, otherwise he received a taste of saline. 2. Of the 1,580 neurons recorded in the orbitofrontal cortex, 3.1% (48) had olfactory responses and 34 (2.2%) responded differently to the different odors in the task. The neurons responded with a typical latency of 180 ms from the onset of odorant delivery. 3. Of the olfactory neurons with differential responses in the task, 35% responded solely on the basis of the taste reward association of the odorants. Such neurons responded either to all the rewarded stimuli, and none of the saline-associated stimuli, or vice versa. 4. The remaining 65% of these neurons showed differential selectivity for the stimuli based on the odor quality and not on the taste reward association of the odor. 5. The findings show that the olfactory representation within the orbitofrontal cortex reflects for some neurons (65%) which odor is present independently of its association with taste reward, and that for other neurons (35%), the olfactory response reflects (and encodes) the taste association of the odor. The additional finding that some of the odor-responsive neurons were also responsive to taste stimuli supports the hypothesis that odor-taste association learning at the level of single neurons in the orbitofrontal cortex enables such cells to show olfactory responses that reflect the taste association of the odor.     

Contributions of the hippocampus, amygdala, and dorsal striatum to the response elicited by reward reduction.

Rats were trained to run down a runway for either 1 or 10 food pellets. After training, those receiving 10 pellets were shifted to 1 pellet. Such shifts typically elicit a temporary decrease in running speed. Groups of normal rats and rats with bilateral lesions of the fimbria–fornix, lateral–basolateral complex of the amygdala, or dorsal striatum were tested with the shifted and unshifted procedures. Separate experiments, identical except for the intertrial intervals (ITIs; 3 min vs. 30 s), were carried out. The data are consistent with the view that an integrated action of multiple neural systems is required to observe the typical response to reward reduction in unlesioned rats. One system that includes the dorsal striatum promotes a reinforced approach response to the goal box. A neural system that includes fimbria–fornix is required to retain information about reduced reward over the 3-min ITI. A system that includes the amygdala may acquire a conditioned aversive response to the goal box after the shift is detected, leading to reduced speeds over testing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neural activity in the primate prefrontal cortex during associative learning

The prefrontal (PF) cortex has been implicated in the remarkable ability of primates to form and rearrange arbitrary associations rapidly. This ability was studied in two monkeys, using a task that required them to learn to make specific saccades in response to particular cues and then repeatedly reverse these responses. We found that the activity of individual PF neurons represented both the cues and the associated responses, perhaps providing a neural substrate for their association. Furthermore, during learning, neural activity conveyed the direction of the animals' impending responses progressively earlier within each successive trial. The final level of activity just before the response, however, was unaffected by learning. These results suggest a role for the PF cortex in learning arbitrary cue-response associations, an ability critical for complex behavior.     

The topographical relationship between two neuronal mosaics in the short wavelength-sensitive system of the primate retina

Adrenocorticotropic hormone (ACTH) secretion from the anterior pituitary is predominantly regulated by corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) synthesized in neurons of the paraventricular nucleus (PVN) of the hypothalamus. Secretion of ACTH occurs in pulsatile bursts. To explore the relationship between hypothalamic control and the pulsatile pattern of ACTH secretion, we measured ACTH in 2 min blood samples over 4 h in rats with intact and lesioned PVN during hypovolemic-stress or control conditions and also measured median eminence (ME) levels of CRH, AVP, and oxytocin (OT). Mean plasma ACTH was highest in the sham lesioned-hypovolemic group, lowest in the sham lesioned-control group and intermediate in the two PVN-lesioned groups. CRH in the ME was negligible in the lesioned animals and correlated with OT and AVP. Pulsatile secretion was observed despite PVN ablation. Visual inspection of composite time series suggested different temporal patterns of ACTH secretion. Principal components analysis of the individual ACTH time series revealed three significant eigenvectors which correlated differentially with the three treatment groups. Neither lesioned group had the steep rise over 10 min seen in plasma ACTH in the non-lesioned groups. Delayed ACTH rise after 30-60 min occurred in all but the sham control group. Our data suggest that CRH is responsible for immediate secretion of ACTH in response to hypovolemic stress and that regulators from non-PVN sites may be responsible for more delayed secretion of ACTH in this setting. The persistence of ME AVP and OT levels in the face of > 90% reduction in ME CRH levels leaves open the question of a role for one or both of these peptides in the delayed ACTH response following stress onset and in the generation of pulsatile ACTH secretory bursts.     

Modulation of neuronal activity by target uncertainty

Visual scenes are composed of many elements and although we can appreciate a scene as a whole, we can only move our eyes to one element of the scene at a time. As visual scenes become more complex, the number of potential targets in the scene increases, and the uncertainty that any particular one will be selected for an eye movement also increases. How motor systems accommodate this target uncertainty remains unknown. The activities of neurons in both the cerebral cortex and superior colliculus are modulated by this selection process. We reasoned that activity associated with target uncertainty should be evident in the saccadic motor system at the final stages of neural processing, in the superior colliculus. By systematically changing the number of stimuli from which a selection must be made and recording from superior colliculus neurons, we found that as the target uncertainty increased, the neural activity preceding target selection decreased. These results indicate that neurons within the final common pathway for movement generation are active well in advance of the selection of a particular movement. This early activity varies with the probability that a particular movement will be selected.     

Effect of nitrous oxide on spinal dorsal horn WDR neuronal activity in cats

The effects of nitrous oxide (75%) on the spinal dorsal born wide dynamic range (WDR) neuronal activity were studied in either spinal cord intact or spinal cord-transected cats. Extracellular activity was recorded in the dorsal horn from single WDR neurons responding to noxious and non-noxious stimuli applied to the cutaneous receptive fields on the left bind foot pads of intact or decerebrate, spinal cord-transected (L 1-2) cats. The experiment was divided into four sections as follows: (1) When 10 micrograms of bradykinin (BK) was injected into the femoral artery ipsilateral to the recording site as the noxious test stimulus in the spinal cord-transected cat, all of 6 WDR neurons gave excitatory responses which were not depressed by 75% nitrous oxide. (2) When the injection of 10 micrograms of BK into the femoral artery ipsilateral to the recording site was used in the spinal cord-intact cat, 6 of 15 WDR neurons (40%) gave excitatory responses, which were significantly depressed by 75% nitrous oxide, and 9 of 15 WDR neurons (60%) gave inhibitory responses, which were not affected by 75% nitrous oxide. (3) When 10 micrograms of bradykinin (BK) was injected into the femoral artery contralateral to the recording site as the noxious test stimulus in the spinal cord transected cat, 6 of 12 WDR neurons gave excitatory reasons, which were not depressed by 75% nitrous oxide. (4) When the injection of 10 micrograms of BK into the femoral artery contralateral to the recording site was used in the spinal cord-intact cat, 6 of 6 WDR neurons (100%) gave responses, which were affected by 75% nitrous oxide. We have observed that nitrous oxide reduces the excitation and inhibition of dorsal born WDR neuronal activities induced by BK injection in spinal cord-intact cats, but does not reduce the excitation of those in spinal cord-transected cats. This finding confirmed that the antinociceptive effect of nitrous oxide might be modulated by supraspinal descending inhibitory control systems. In addition our result showed that the supraspinal effect of nitrous oxide was mediated not only by an increase but also a decrease in a supraspinal descending inhibition.     

Spontaneous activity: functions of calcium transients in neuronal differentiation

Calcium ions play critical roles in neuronal development. Many excitable cells promote calcium influx across their surface membrane during early stages of differentiation, which can trigger further elevation of intracellular calcium by release from stores. Several distinct types of spontaneous elevations of intracellular calcium occur during development of amphibian spinal neurons, both in culture and in the intact spinal cord. Rapid spikes and slow waves originate by different mechanisms and have separate functions. Spikes are required for neurotransmitter expression and channel modulation. Waves occurring in growth cones appear to regulate neurite extension.