Influence of acetylcholine on neuronal activity in monkey orbitofrontal cortex during bar press feeding task

Cholinergic involvement in feeding-related neuronal activity was investigated in the orbitofrontal cortex (OBF) of the behaving monkey by means of a microiontophoretic application of acetylcholine (ACh) and atropine. The activity of ACh sensitive cells did not correlate with any particular event during the bar press feeding task. Atropine blocked the excitatory response to ACh and task events. The results suggest that the cholinergic system in the monkey OBF regulates excitatory neuronal responses in several phases of motivated behavior.     

Influence of acetylcholine on neuronal activity of monkey amygdala during bar press feeding behavior

Single neuron activity in the monkey amygdala was investigated during cue signalled conditioned bar press feeding behavior and the effects of electrophoretically applied acetylcholine (ACh) and atropine were analyzed. ACh increased the firing rate of one third of the neurons tested; these excitatory responses were inhibited by the muscarinic receptor antagonist atropine. No characteristic location of ACh-sensitive neurons was found, cells were diffusely distributed throughout the amygdala. Activity of ACh-sensitive neurons did not correlate with any particular event during the bar press feeding task. However, continuous application of ACh at low current intensity during the task significantly enhanced the task-related excitatory firing patterns, or markedly attenuated the inhibitory responses. Continuous application of atropine elicited or enhanced inhibitory response patterns. These results suggest that the cholinergic system of the monkey amygdala facilitates neuronal excitation but attenuates inhibition related to various phases of feeding behavior, such as to cue recognition, food aquisition and rewarding process.     

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 depend 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 feed 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.

     

Neuronal activity in the ventral tegmental area (VTA) during motivated bar press feeding in the monkey

Neuronal activity of 58 dopaminergic (DA) and 200 non-dopaminergic (non-DA) neurons in the ventral tegmental area (VTA) of female monkeys was recorded, and correlation to bar press feeding, sensory stimulation and change in motivation was investigated. DA neurons, judged by duration of action potentials (more than 2.5 ms) and responsiveness to apomorphine, had lower firing rates (0-8 impulses/s); non-DA neurons had intermediate firing rates (10-30 impulses/s). Two-thirds of the DA and non-DA neurons responded in bar press feeding; the former with mostly tonic and the latter with phasic responses. Fifteen neurons (5%) responded phasically to arm extension toward the bar, 124 (excitation 88, inhibition 36, 45%) during bar press (BP), and 91 (excitation 32, inhibition 59, 33%) during ingestion reward (RW). Most BP responses (84/124, 68%) continued tonically throughout the BP period with no correlation to each BP movement. In 14 neurons (14/124, 11%), firing showed a specific variation: transient early BP responses shifted to tonic steady ones in palatable food trials, and the shifts correlated well with BP speed. In 20 other neurons, firing increased during BP hip lifting, and at specific vocalization to ask for food; it decreased during food ingestion, drinking and inguino-crural stimulation. Apomorphine administration decreased firing for the first 5-15 min, then increased it with frequent lip smacking, nausea, involuntary movement and vocalization. Thus VTA neurons showed mostly steady tonic responses but some specific phasic responses. They responded not only to motor events but also in close relation to changes of motivational aspects. Neuronal responses were excitation during procurement of reward and inhibition during or after perception of reward. This modulation in firing, might be important in the initiation and execution of movement and/or motivated behavior.     

Movement and non-movement related pallidal unit activity during bar press feeding behavior in the monkey

Activity was recorded from 358 neurons in the globus pallidus (GP) of monkeys (Macaca fuscata) during an operant feeding task consisting of 3 stages: (1) food or non-food presentation (1st stage); (2) bar pressing (2nd stage); and (3) food acquisition and ingestion (3rd stage). There were two kinds of neurons, one with high and the other with very low (almost silent), spontaneous firing rates. Two hundred and four neurons (57%) responded in one or more of the feeding stages. Of the 21 neurons which responded in the 1st stage, two responded selectively to food presentation, and 19 responded to both food and non-food visual presentation. One hundred and seventy-four neurons (49%) and 107 neurons (30%) responded in the 2nd and 3rd stages, respectively, and 106 (30%) of these were directly related to specific feeding motor acts such as arm extension, flexion, bar pressing, grasping, chewing etc. Both high and low firing neurons responded to motor acts with sharp or gradual onset. More than half of those that responded to arm extension showed laterality (contra or ipsi)- and function (extension or flexion)-dependent responses. The incidence of the motor related neurons was higher in the caudodorsal part of the GP. On the other hand, about one third, especially in the rostroventral part of the GP, 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 non-food or during forcible ingestion. The magnitude of firing changes during arm extension and bar pressing depended on the nature of the food. Moreover, in trials using new food or false (model) food, firing changes during bar press appeared or disappeared within a few trials with no correlation to bar press movement. These data suggest heterogeneous functions within the GP; the caudodorsal part is strictly concerned with motor execution and preparation, while the rostroventral part is not related to motor function directly, but may rather be important in coupling internal, motivational information to the motor system.     

Internal and external information processing by lateral hypothalamic glucose-sensitive and insensitive neurons during bar press feeding in the monkey

Single neuron activities in the lateral hypothalamic area (LHA) were recorded during bar press feeding task in the monkey. First registered neurons were sorted into 2 groups, glucose-sensitive (GS) and glucose-insensitive (GIS) neurons, depending on their glucose sensitivity. Then firing variations to feeding, electrophoretically applied catecholamines and opiate, and to odor and taste stimuli were investigated. GS neurons responded to dopamine, noradrenaline and morphine more often than GIS neurons. In feeding task GS neurons responded during bar press (BP) and reward (RW) periods with long-lasting inhibition of firing and at cue tone (CT) with transient inhibition, while GIS neurons responded during BP and RW periods mainly with excitation and at cue light (CL) with excitation. A majority of GS neurons responded to both odor and taste stimuli more often than GIS neurons. Data suggest that these two kinds of neurons in the LHA may be involved in different functional aspects of feeding: GS neurons, mainly in internal information processing and reward mechanism, and GIS neurons, in external information processing and motor aspects.     

Neuronal responses in monkey lateral hypothalamus during operant feeding behavior

Single neuron activity was recorded from monkey lateral hypothalamus to investigate neuronal events correlated with operant bar press feeding behavior. The behavioral paradigm was divided into three phase: visual (discrimination), bar press (procurement), and ingestion (consummatory). Of 669 neurons tested, 158 (24%) responded in one or more phases. During the visual phase, 106 neurons (16%) responded. Of 80 neurons that responded in the visual phase and were tested systematically, 33 (41%, 33/80) responded selectively to the sight of food or nonfood objects associated with a juice reward, but not to the sight of nonfood or objects associated with aversive saline. Neuronal activity related to discrimination was modulated by satiation and learning (i.e., acquisition and extinction). During the bar press phase, 51 neurons (7.6%) responded. These responded tonically during the early or late stage of the bar press period, but did not depend on individual bar pressing motions. During ingestion, 90 neurons (13%) responded. The ingestion response was modulated by palatability of food and satiation. Data suggest that the LHA is deeply involved in operant feeding behavior; discrimination of food, drive to get food, and perception of reward, all of which are affected by learning and internal states such as hunger and satiety.     

Dopaminergic unit activity in freely moving cats: Lack of relationship to feeding, satiety, and glucose injections

The activity of dopaminergic neurons in the substantia nigra was recorded from freely moving cats during feeding and satiety, and following injections of glucose. At no time during feeding or in the postprandial satiety period was there a significant increase or decrease in firing rate of these neurons relative to baseline. Additionally, no change in firing rate was observed following injections of glucose (300, 500 and 1000 mg/kg) or glucose in combination with insulin (300 mg/kg glucose and 0.8 units/kg insulin).     

Single neuronal responses in medial prefrontal cortex during cocaine self-administration in freely moving rats

Chronic single neuronal recording techniques were applied to investigate the involvement of the medial prefrontal cortex (mPFC) during cocaine self-administration in the rat. Rats were trained to press a lever for cocaine under continuous reinforcement and fixed ratio schedules. Different patterns of phasic neuronal activity changes were found to be associated with lever-pressing for cocaine. The neuronal responses could be classified into five categories: 1) increases in neuronal firing before the lever press (15 out of 121 neurons, 12.4%); 2) decreases in neuronal firing before the lever press (13 neurons, 10.7%); 3) increases in neuronal firing after cocaine infusion (4 neurons, 3.3%); 4) decreases in neuronal firing after cocaine infusion (32 neurons, 26.4%); and 5) no alteration of neuronal activity throughout the self-administration session (67 neurons, 55.4%). The anticipatory responses, i.e., neuronal activity appearing before the lever press, were observed for both the continuous reinforcement and fixed ratio schedules. In a few cases, alteration of firing rate was not observed for the first lever press but appeared before subsequent lever presses in fixed ratio schedules. Eliminating cocaine abolished the inhibitory neuronal responses observed after lever press, suggesting that these inhibitory responses after cocaine self-administration were attributable to the pharmacologic effect of cocaine. The data provide initial electrophysiological evidence that the mPFC may play a role in mediating the task sequencing which leads to cocaine self-administration. Synapse 26:22–35, 1997. © 1997 Wiley-Liss, Inc.     

Functional heterogeneity of the monkey lateral hypothalamus in the control of feeding

Regional differences in the effects of electrical (ES) and chemical stimulation on execution of a bar-press feeding task, and in neuronal activity related to feeding, glucose sensitivity, and odor responsiveness were examined in the lateral hypothalamic area (LHA) of monkeys. In satiated animals, ES of the far lateral and ventral LHA induced bar-press feeding. In hungry animals, ES of the dorsal LHA suppressed the feeding task only during the stimulation period, but prolonged feeding suppression that occurred after ES of the ventromedial LHA. Microinjection of Na-glutamate into LHA sites where ES was effective in suppressing feeding had no effect, but it was effective in the medial hypothalamus. Glucose-sensitive (GS) neurons decreased in activity during bar pressing and/or during the ingestion period. Glucose-insensitive (GIS) neurons showed a cue-related excitation more often than GS neurons. Odor-responding GS and GIS cells were localized in ventromedial and lateral LHA sites, respectively. The present study suggests the regional heterogeneity of the LHA in feeding regulation, depending on both hunger and satiety states.     

Complex attributes of lateral hypothalamic neurons in the regulation of feeding of alert rhesus monkeys

To elucidate the roles of glucose-sensitive (GS) and glucose-insensitive (GIS) cells of the lateral hypothalamic area (LHA), single neuron activity was recorded during 1) microelectrophoretic administration of chemicals, 2) a conditioned bar press feeding task, 3) gustatory, 4) olfactory, and 5) electrical brain stimulation. GS and GIS neurons showed different firing rate changes during phases of the task, and the responses were highly influenced by the palatability of the food and the motivational (hunger or satiety) state of the animal. The two groups of cells also differed in their responsiveness to gustatory and olfactory stimuli: GS neurons were more likely to respond to tastes and odors than GIS cells. Taste- and odor-responsive GS neurons were primarily suppressed by electrophoretically applied noradrenaline and were localized ventromedially within the LHA. The chemosensitive GIS cells, being organized along a dorsolateral axis, were especially excited by dopamine. The two sets of neurons had distinct connections with associative (orbitofrontal, prefrontal) cortical areas. GS and GIS cells, thus, appear to have differential and complex attributes in the control of feeding.     

Hunger Modulates the Responses to Gustatory Stimuli of Single Neurons in the Caudolateral Orbitofrontal Cortex of the Macaque Monkey

1. In order to determine whether the responsiveness of neurons in the caudolateral orbitofrontal cortex (a secondary cortical gustatory area) is influenced by hunger, the activity evoked by prototypical taste stimuli (glucose, NaCl, HCl, and quinine hydrochloride) and fruit juice was recorded in single neurons in this cortical area before, while, and after cynomolgous macaque monkeys were fed to satiety with glucose or fruit juice. 2. It was found that the responses of the neurons to the taste of the glucose decreased to zero while the monkey ate it to satiety during the course of which his behaviour turned from avid acceptance to active rejection. 3. This modulation of responsiveness of the gustatory responses of the neurons to satiety was not due to peripheral adaptation in the gustatory system or to altered efficacy of gustatory stimulation after satiety was reached, because modulation of neuronal responsiveness by satiety was not seen at earlier stages of the gustatory system, including the nucleus of the solitary tract, the frontal opercular taste cortex, and the insular taste cortex. 4. The decreases in the responsiveness of the neurons were relatively specific to the food with which the monkey had been fed to satiety. For example, in seven experiments in which the monkey was fed glucose solution, neuronal responsiveness decreased to the taste of the glucose but not to the taste of blackcurrant juice. Conversely, in two experiments in which the monkey was fed to satiety with fruit juice, the responses of the neurons decreased to fruit juice but not to glucose. 5. These and earlier findings lead to a proposed neurophysiological mechanism for sensory-specific satiety in which the information coded by single neurons in the gustatory system becomes more specific through the processing stages consisting of the nucleus of the solitary tract, the taste thalamus, and the frontal opercular and insular taste primary taste cortices, until neuronal responses become relatively specific for the food tasted in the caudolateral orbitofrontal cortex (secondary) taste area. Then sensory-specific satiety occurs because in this caudolateral orbitofrontal cortex taste area (but not earlier in the taste system) it is a property of the synapses that repeated stimulation results in a decreased neuronal response. 6. Evidence was obtained that gustatory processing involved in thirst also becomes interfaced to motivation in the caudolateral orbitofrontal cortex taste projection area, in that neuronal responses here to water were decreased to zero while water was drunk until satiety was produced.     

Catecholaminergic mechanisms of feeding-related lateral hypothalamic activity in the monkey

The functional role of the catecholaminergic mechanism in the lateral hypothalamus (LHA), in feeding behavior of the monkey was investigated by single neuron activity recording and electrophoretic application of dopamine (DA), noradrenaline (NA) and their antagonists. The feeding paradigm had 4 phases: cue light (CL) signaled start of bar press; bar press (BP, 20-30 times); short cue tone (CT) triggered by last bar press signaled presentation of food; and ingestion-reward (RW). Of 312 neurons tested, 189 (61%) responded in one or more phases of the feeding task. Two types of response were observed: CL- or CT-related transient, and BP- or RW-related long-lasting responses. These feeding-related responses depended on the nature of the food and on the hunger-satiety level. DA excited or inhibited different neurons, while NA mainly inhibited firing. DA-sensitive neurons responded more often in the feeding task than insensitive neurons due mainly to differences in responsiveness to CL on (chi 2 test, P less than 0.01), at motor initiation, and during BP (P less than 0.05). Spiperone blocked the former two responses. NA-sensitive neurons responded more often in the feeding task due to responsiveness during BP and RW (P less than 0.01). Sotalol blocked some BP-related responses, and phenoxybenzamine and sotalol blocked the CT-related responses. The data suggest that dopaminergic and noradrenergic inputs in the LHA are crucial in task initiation and reward processing, respectively. Integration of these catecholaminergic and other inputs in the LHA might be important in accomplishing motivated feeding.     

Visual responses related to food discrimination in monkey lateral hypothalamus during operant feeding behavior

Single neuron activity was recorded from monkey lateral hypothalamic area (LHA) to relate neuronal events to food discrimination and initiation of procurement movement in operant bar press feeding behavior. Of 429 neurons tested, 68 (16%) responded during visual phase. Of these, 30 (7%) responded selectively to the sight of food or non-food associated with a juice reward, but not to the sight of meaningless non-food or food associated with aversive saline. Neuronal activity related to discrimination was readily influenced by extinction, reversal or satiation. The strength of visual responses was correlated with latency of bar press initiation and speed of bar pressing, but was not related directly to bar press movement. These suggest that the LHA is deeply involved in discrimination of reinforcement or non-reinforcement, and might be associated with higher functions to regulate internal states such as physiological need to get food during operant feeding behavior.     

Opiate mechanism in reward-related neuronal responses during operant feeding behavior of the monkey

Reward-related neuronal activity and its modulation by morphine and naloxone was investigated by extracellular single neuron recording and electrophoretic application of drugs in the lateral hypothalamus, during operant feeding of the monkey. Morphine-sensitive neurons responded more often during bar press and ingestion-reward phases. Naloxone blocked only ingestion-reward responses, especially the inhibitory ones. The results suggest that the central opiate system can be involved in reward-related neuronal responses in the lateral hypothalamic area of the monkey.     

Effects of hunger on the responses of neurons in the lateral hypothalamus to the sight and taste of food

Recordings were made from single neurons in the monkey lateral hypothalamus and substantia innominata which had previously been shown to respond with an increase or decrease of their firing rates when the hungry monkey tasted food, and/or when he looked at food. It was found that the responsiveness of these neurons to food decreased over the course of a meal of glucose as satiety increased. When satiety, measured by whether the monkey rejected the glucose, was complete, there was no response of the neurons to the taste and/or to the sight of glucose. The spontaneous firing rates of these cells were not affected by the transitions from hunger to satiety. This modulation of responsiveness to food of hypothalamic cells was specific to them in that it was not seen in cells in the globus pallidus which responded in relation to swallowing and mouth movements, or in cells in the visual inferotemporal cortex which responded when the monkey looked at the glucose-containing syringe. On the basis of this and other evidence it is suggested that the hypothalamic cells described here could be involved in the autonomic, the endocrine, and/or the feeding responses which occur when an animal sees or tastes food.     

Behavioral significance of monkey hypothalamic glucose-sensitive neurons

Feeding-related neuronal activity of lateral hypothalamic glucose-sensitive and glucose-insensitive neurons was investigated in behaving monkeys. The behavioral paradigm was a high fixed ratio of bar pressing for food reward signaled by light and tone cues. Twenty-seven percent of the neurons tested were glucose-sensitive. The population of neurons which changed in firing rate during the feeding task was higher among glucose-sensitive cells than among glucose-insensitive cells. The activity of many glucose-sensitive neurons decreased during the bar pressing and reward periods. A small population of glucose-sensitive neurons responded to cue stimuli. The results suggest that glucose-sensitive neurons are mainly involved in the drive and/or reward mechanism of feeding behavior, and that these cells may have specific roles in neural control of hunger-motivated food acquisition.     

Monkey orbitofrontal neuron activity during emotional and feeding behaviors

Long term, single neuron activity was recorded in the monkey orbitofrontal cortex (OBF) through chronic platinum-iridium microwire electrodes. Tonic as well as phasic changes in neuronal activity occurred upon presentation of palatable (food) and aversive stimuli during bar pressing for food. Lesions in this region are known to induce changes in emotional behavior. Therefore, the results suggest that the OBF neurons are involved in processing emotion.     

Cortical visual areas process intestinal information during slow‐wave sleep

Background Previously we have shown that, during sleep, electrical and magnetic stimulation of areas of the stomach and small intestine evoked neuronal and EEG responses in various cortical areas. In this study we wanted to correlate natural myoelectrical activity of the duodenum with cortical neuronal activity, and to investigate whether there is a causal link between them during periods of slow‐wave sleep. Methods We have recorded the myoelectrical activity from the wall of the duodenum and activity of single neurons from three cortical visual areas in naturally sleeping cats and investigated causal interrelationship between these structures during slow‐wave sleep. Key Results About 30% of the cortical neurons studied changed their firing rate dependent on the phases of the peristaltic cycle and demonstrated selectivity to particular pattern of duodenal myoelectrical activity during slow‐wave sleep. This interrelationship was never seen when awake. Conclusions & Inferences This observation supports the hypothesis that, during sleep, the cerebral cortex switches from processing of exteroceptive and proprioceptive information to processing of interoceptive information.     

Sleep and wakefulness modulation of the neuronal firing in the auditory cortex of the guinea pig

Sleep-related changes—including modification in sensory processing—that influence brain and body functions, occur during both slow wave and paradoxical sleep. Our aim was to investigate how cortical auditory neurons behave during the sleep/waking cycle, and to study cell firing patterns in relation to the processing of auditory information without the interference of anesthetic drugs. We recorded single cells in the A region of the auditory cortex in restrained, chronically-implanted guinea pigs, and compared their evoked and spontaneous activity during sleep stages and quiet wakefulness. A new classification of the unit's responses to simple sound during wakefulness is presented. Moreover, a number of the neurons in the primary auditory cortex exhibited significant quantitative changes in their evoked or spontaneous firing rates. These changes could be correlated to sleep stages or wakefulness in 42.2% to 58.3% of the sampled neurons. A similar population did not show behavioral related changes in firing rates. Our results indicate that the responsiveness of the auditory system during sleep may be considered partially preserved. An important result was that spontaneous and evoked activity may vary in opposite directions, i.e., the evoked activity could increase while the spontaneous activity decrease or vice versa. Then, a general question was proposed: is the increased spontaneous activity in the auditory cortex, particularly during PS, related to auditory hypnic ‘images'? The studied cortical auditory neurons exhibit changes in their firing rates in correlation to stages of sleep and wakefulness. This is consistent with the hypothesis that a general shift in the neuronal networks involved in sensory processing occurs during sleep.