Peter M. Milner

The legacy of Donald O. Hebb: more than the Hebb Synapse

Neuroscientists associate the name of Donald O. Hebb with the Hebbian synapse and the Hebbian learning rule, which underlie connectionist theories and synaptic plasticity, but Hebbs work has also influenced developmental psychology, neuropsychology, perception and the study of emotions, as well as learning and memory. Here, we review the work of Hebb and its lasting influence on neuroscience in honour of the 2004 centenary of his birth.

Plasticity of the medial prefrontal cortex: Facilitated acquisition of intracranial self-stimulation by pretraining stimulation

Prior electrical stimulation of the medial prefrontal cortex MFC facilitated the subsequent acquisition of intracranial self-stimulation (ICSS) from the same MFC electrode site. Stimulations that were spaced over a period of six days were more effective in producing this facilitation than the same number of stimulations delivered over a two day period. These data suggest that the rewarding effects of MFC stimulation may involve some process akin to the kindling phenomenon and as such may provide insights in the neuronal modifications thought to underlie learning and memory.

Neural representations: Some old problems revisited

Hebbs (1949) cell assembly, originally conceived as an explanation for stimulus equivalence, also serves as a neural representation of stimuli. Association between cell assemblies was a major theme of Hebbs book, but the state of physiological knowledge at the time was such that no satisfactory basis for it could he devised. Subsequent theory has been more concerned with the recognition and attractor features of the cell assembly than its capacity to represent and associate concepts. This is unfortunate because while generalization is important, so is discrimination, which is not well served by an attractor model. This dilemma is avoided by postulating that stimulus representation and stimulus equivalence involve different neural circuits. Human beings can instantly form and use associations between many more concepts than there are synapses on the average cortical neuron, indicating that the associative links between engrams are sparse. The connections within an engram, on the other hand. must be dense to ensure that a weak input can activate all its neurons. It would appear that two processes are anatomically and physiologically different, which may account for the fact that engrams remain distinct in spite of being associated with each other. The fact that a single concept may have very many associations puts a heavy demand on the process of selective attention to avert complete chaos. I propose that attention is a manifestation of motivation. Motivation facilitates responses, which in turn facilitate engrams of associated stimuli. The enhanced engram activity is fed back through centrifugal paths to intensify sensory input that has previously played a part in executing the planned responses. Attention may also contribute to a mechanism that prevents the engrams of component parts of an object from being assimilated into the engram of the whole.

Elimination of medial prefrontal cortex self-stimulation following transection of efferents to the sulcal cortex in the rat

Intracranial self-stimulation (ICSS) of the medial prefrontal cortex (MFC) was not affected by lesions of the medial forebrain bundle, the nucleus accumbens or medialis dorsalis. However, bilateral, parasagittal knife cuts that transected fibers interconnecting the medial and sulcal cortices eliminated ICSS from the MFC with no apparent recovery over a 21 day test period. Similar knife cuts produced only transient effects on lateral hypothalamic ICSS. These data suggest that the neural substrates of frontal cortex ICSS are very different than those that subserve ICSS along the medial forebrain bundle.

Development of brain stimulation reward in the medial prefrontal cortex: facilitation by prior electrical stimulation of the sulcal prefrontal cortex.

Electrical stimulation of the medial prefrontal cortex (MC) in rats delivered daily for seven days causes a marked improvement in the rate of acquisition of a self-stimulation response. In the present experiment, we looked at whether we could get the same facilitatory effect on self-stimulation of the MC by delivering pre-training stimulation to other points in the brain anatomically related to the MC. Electrical stimulation of the lateral hypothalamus was without effect. However, electrical stimulation of the sulcal prefrontal cortex (SC) either contralateral or ipsilateral to the MC electrode did facilitate acquisition of self-stimulation of the MC. Thus the Sc and MC would appear to be part of the same substrate controlling the development of positive reinforcement in the MC.

The discovery of self-stimulation and other stories

The authors recollections of the events leading to the discovery of rewarding brain stimulation at McGill University in 1953, with a history of his subsequent attempts to find a learning theory congruent with the phenomenon.

Effects of dopamine supersensitivity on lateral hypothalamic self-stimulation in rats

Dopamine (DA) receptor supersensitivity was demonstrated by potentiated d-amphetamine stereotype after a three-day treatment regimen in which the DA receptor blocker pimozide (4.0 mg/kg) was administered twice daily. Similarly-induced DA supersensitivity produced a significant increase in the rate of lever-pressing for lateral hypothalamic (LH) intracranial self-stimulation (ICSS) and a significant decrease in ICSS thresholds. No change from pretreatment baselines was observed in vehicle-treated control animals. Following three-day treatment with the noradrenaline--(NA) and DA-receptor blocker, haloperidol (4.0 mg/kg twice daily), a single injection of the alpha-adrenergic agonist clonidine (0.15 mg/kg) caused increased running behavior. In contrast clonidine decreased running in rats pretreated with chronic pimozide or vehicle. These results indicate an increase in the sensitivity of central NA receptors following chronic haloperidol but not chronic pimozide. Taken together, these findings were interpreted as a potentiation in the reinforcing properties of LH-ICSS after chronic pimozide treatments due to increases in the sensitivity of DA and not NA receptors.

Treatment with anticonvulsant drugs retards the development of brain-stimulation reward in the prefrontal cortex

Electrical stimulation of the medial prefrontal cortex in rats daily for nine days caused a marked improvement in the rate of acquisition of a self-stimulation response. Diazepam (1 mg/kg, IP) or phenobarbital (15 mg/kg), but not phenytoin (25 mg/kg), administered during the nine day period of electrical stimulation, attenuated this facilitatory effect. However, diazepam or phenobarbital in the same dosages administered to self-stimulating rats (i.e., after acquisition) failed to alter responding. It was suggested that a kindling-like mechanism may underlie the development of self-stimulation of the prefrontal cortex.

Theories of Reinforcement, Drive, and Motivation

It is the aim of psychological research to explain behavior, and physiological psychologists believe that the most—possibly the only—satisfactory explanation is in terms of neural functioning. Successfully relating data at one level to data at a different level requires a good theoretical framework; physical chemistry, for example, would be impossible without a theory of elements and of the atomic nature of chemical reactions, and no simple explanation of celestial motion in terms of gravitational and inertial forces would be possible starting from the assumption that the earth is stationary.

Response involvement in brain stimulation reward

Abstract The hypothesis that responding contributes to the reward value of brain stimulation was tested in two novel experimental paradigms. In the first experiment rats lever-presssed for rewarding brain stimulation during 90 sec periods. After each period the lever automatically retracted and experimenter-administered stimulation (EAS) was presented at the same rate and current parameters as during the self-stimulation (SS). The rats could demonstrate a preference for SS (vs EAS) by pressing a reset lever on the opposite wall of the test chamber. This action terminated the EAS and reinstated the SS-lever for an additional 90 sec. Results showed that the rats preferred to respond for stimulation than to have that same stimulation administered by the experimenter. This was true even when a signal preceded each train of EAS or when subjects had a great deal of previous EAS experience. In the second experiment conditioned taste preferences were observed following novel taste/SS pairings but not following novel taste/EAS pairings. The data from these two experiments suggest that responding contributes to the rewarding value of brain stimulation.