James Olds

Self-Stimulation of the Brain: Its Use To Study Local Effects of Hunger, Sex, and Drugs

My conclusions are these: (i) The cells which mediate primary rewarding effects are located in a midline system running from the midbrain through the hypothalamus and midline thalamus and into the subcortical and cortical groups of the rhinencephalon. (ii) The cell groups which mediate primary rewarding effects are different from those which mediate primary punishing effects. (iii) Despite this relative independence, there are, undoubtedly, relationships of mutual inhibition existing between these two systems. Rewards do, among other things, tend to reduce sensitivity to pain, and punishments do tend to reduce rewarding effects. (iv) These primary reward systems of the brain are subdivided into specific drive-reward subsystems mediating the specific drives such as hunger and sex. (v) Because there are also subsystems of this set of rewarding structures sensitive to different chemical effects, it is reasonable to hope that eventually it will be possible to control the reward systems pharmacologically in cases where behavior disorders seem to result from deficits or surfeits of positive motivation.

Identical "Feeding" and "Rewarding" Systems in the Lateral Hypothalamus of Rats

Electrodes were implanted in the lateral hypothalamic feeding system; animals were subjected to both feeding and motivational tests. All animals that demonstrated stimulus-bound feeding behavior also showed high self-stimulation rates. As it was impossible to produce the feeding response without simultaneously producing the rewarding effect of hypothalamic stimulation, it was concluded that the feeding system of the lateral hypothalamus is one among a larger group of places where stimulation causes primary rewarding effects. With electrodes in these same areas, food deprivation often caused a major increment in the self-stimulation rate.

Hippocampal Unit Activity during Classical Aversive and Appetitive Conditioning

Rats were trained with a tone being followed by either food or electric shock, on alternate days. Unit activity during application of the conditioned stimulus was recorded from the dorsal hippocampus. The results indicate differentiation of the hippocampal system. Dentate units respond by augmentation to a conditioned stimulus which leads to food and by inhibition to the same stimulus when it precedes electric shock. The hippocampus proper responds by augmentation in both situations. The intensity of the hippocampal response to the conditioned stimulus on the first day of training is higher if the unconditioned stimulus is food than if it is electric shock. These data cast light on the functions of the dorsal dentate-hippocampal connections and the hippocampus proper during aversive and appetitive conditioning.

A motivational analyses of the reticular activating system

Abstract In 51 rats electrode pairs were chronically implanted with spacing 1 mm. apart from rat to rat to make a grid of the tegmentum. In each case three tests were made: a self-stimulation test for positive reinforcement; an escape test for negative reinforcement; and an EEG test for cortical arousal. The main results were these: all points yielding escape at very low thresholds were clustered in the dorso-medial tegmentum just below the tectum and just lateral to the central grey; all points yielding self-stimulation at high rates were clustered ventrally, usually below and lateral to the medial lemniscus; and points yielding arousal at very low thresholds were clustered in the lateral tegmentum, half-way up from the ventral surface. As for interactions between the three effects, all points yielding escape at low thresholds also yield arousal at low thresholds; al points yielding self-stimulation at high rates yielded arousal at moderately high thresholds; and some points yielded both moderate escape and moderate self-stimulation. Finally, there definitely were points which yielded arousal at low thresholds and which yielded no other motivational effects.

Neurons in Paradoxical Sleep and Motivated Behavior

Single-cell recordings were taken with electrodes permanently implanted in unrestrained rats during normal sleep, paradoxical sleep, quiet awake, and highly motivated awake periods. In most areas, neuronal activity increased when normal sleep changed to paradoxical sleep. The hypothalamus showed a significantly greater increase than most other areas. The hippocampus differed strikingly from all other areas by showing a decrement in all cases. The average firing rates in paradoxical sleep exceeded those of the quiet awake state as well as those of normal sleep. Comparison of paradoxical sleep with motivated behavior illustrated that changes in brain activity during paradoxical sleep were related to anatomically specifiable groupings, but no such differentiation appeared in motivated behavior.

Single unit patterns during anticipatory behavior

Abstract 1. 1. Animals with several fine-wire electrodes implanted chronically in the brain for single unit recordings were pre-trained to immobilize themselves for brief intervals in order to obtain food or water. Unit activity was recorded simultaneously from 4 probes in each animal during these periods of immobilization and in other quiet intervals during wakefulness and sleep. Groups of from 7 to 20 probes were studied in each of the following areas: hippocampal, preoptic, lateral hypothalamic, ventral tegmental, thalamic, ventral reticular and dorsal reticular. 2. 2. Relatively large and stable changes in neuronal activity were noted in the course of the brief waiting periods. In dorsal reticular formation, thalamus and ventral tegmentum changes were regularly in the positive direction, neurons firing more rapidly as the reinforcing stimulus became more imminent. In the neuronal activity of hippocampus, preoptic area, ventral reticular. formation and hypothalamus, there was more variability between neurons; the firing rate would show either a decrement or on increment or no change depending on the particular unit involved. 3. 3. In individual experiments the activity of some neurons seemed to be especially related to either food or water behavior; these elements were more frequently found in the hippocampus, hypothalamus and preoptic area, the largest number appearing in area CA-3 of hippocampus.

Midbrain unit activity during classical conditioning.

In behaving rats, unit activity recorded from the ventral tegmentum and from the reticular formation was monitored during classical conditioning. Rewarding electric stimulation of the medial forebrain bundle was used as the unconditioned stimulus (UCS). Only those cells possessing prior responses to the conditioned stimulus (CS) changed their responses as a result of conditioning. Responses recorded from cells which were driven by both the auditory CS and the brain shock UCS were significantly more often changed than those driven by the CS alohe. These data show that the auditory and brain shock fields of influence interact in at least some brain regions prior to conditioning and that pairing the two kinds of stimuli is more likely to influence auditory responses recorded from these regions than those recorded elsewhere. It is possible to imagine that the intersection of the two fields is a sine qua non of conditioning and that the two prior actions caused the change by interacting at or near the recording point.

Conditioned responses of hippocampal and other neurons

Abstract Changes in the firing rates of neurons in various subcortical structures induced by application of a 1 sec auditory stimulus were recorded in unrestrained animals during movement-free intervals. Pseudo-conditioning trials (500) were followed by conditioning trials (300). During the latter, a food pellet was presented to the animal by a dispenser after every stimulus, provided there was no detectable movement during the stimulus period. The difference between the response rates before conditioning and after conditioning was considered to be a measure of the effect induced by the conditioning procedure. 1. 1. Except for the early response in the dorsal reticular formation, responses consisting of incremental firing rate were increased in size and number and decremental response were attenuated or reversed. Even in the dorsal reticular formation the neuronal activity rate during the last half of the stimulus was augmented. 2. 2. Before conditioning an increment in the firing rate of neurons appeared in most areas during the first 300 msec of stimulation after which the firing rate returned almost to control levels or even systematically below control levels in some areas. In most cases, conditioning procedures caused the early increment to be augmented and the neuronal rate to stay elevated above control levels during the remainder of the 1 sec stimulus (thus reversing the decremental tendency where it had appeared). 3. 3. Incremental changes were largest in hippocampus. These changes were, on the basis of deductive arguments, considered to be independent of skeletal and attentional components of the conditioned response on the one hand, and unrelated to sleep and waking or inhibitory processes on the other. It seemed possible therefore that the changes might be related to a short term or temporary trace of a motivationally significant event.

Units during habituation, discrimination learning, and extinction☆

Abstract Unit responses were recorded with 62.5 μ fine wires implanted chronically in rats. In each animal simultaneous recordings were made from four probes: in hippocampus, midbrain, hypothalamus and preoptic area. Hippocampal units did not respond in a special fashion to novel stimuli and what responses there were did not change during habituation. After this, response increments appeared rapidly in hippocampus during conditioning, and at the same time a difference developed between the hippocampal firing rates induced by the CS+ and CS− control stimulus. In extinction, the responses in hippocampus changed again to a level between the habituation level and the conditioning level. In other words, complete extinction of the increments in firing rates brought on by conditioning 0did not occur. Midbrain units responded to novel stimuli initially, and then showed clear and continuous habituation during the preliminary series of trials. They showed increments in rate of discharge during conditioning; and a difference between patterns of firing induced by CS+ and CS− developed gradually as compared to its rapid appearance in the hippocampus. The midbrain pattern of neuron responses which appeared during conditioning disappeared during extinction. Hypothalamic units showed patterns of neuron responses somewhat similar to those of midbrain units but less pronounced. Preoptic units showed relatively small responses to novel stimuli but these disappeared rapidly during habituation and there were no further responses in the series of conditioning or extinction trials.

Dissociation of self-stimulation and epileptiform activity

Abstract 1. 1. Ventrolateral tegmental stimulation caused self-stimulation behavior at very high rates but no epileptiform discharges even with much higher current levels. 2. 2. Posterior lateral hypothalamic stimulation caused self-stimulation and (at higher current levels) random spikes which were unrelated to self-stimulation: that is, (a) they did not stop self-stimulation and (b) they appeared even in cases where self-stimulation did not. 3. 3. Anterior lateral hypothalamic stimulation and septal region stimulation caused self-stimulation and (at higher intensity levels) organized epileptiform after-discharges which usually caused self-stimulation behavior to cease for a period during, and a few seconds after the abnormal electrical discharges. 4. 4. Epithalamic and posterior lateral thalamic stimulation sometimes caused self-stimulation; stimulation of these areas also often caused one or the other of the epileptiform patterns described above. 5. 5. For all probes clearly yielding both effects, thresholds for self-stimulation were lower than those for epileptiform discharges during the period of initial tests. However, at a later date (about two months after surgery) epileptiform thresholds were below self-stimulation thresholds in some cases with probes in the anterior lateral hypothalamus or septal area. 6. 6. The random spikes provoked by stimulation in the posterior lateral hypothalamus spread preferentially to tegmental and thalamic probes and much less, if at all, to septal or anterior lateral hypothalamic probes. The organized discharges provoked by stimulation of anterior lateral hypothalamus, septal area, and epithalamus spread preferentially to other members of this triadic group.