Bielajew C, Shizgal P. Evidence implicating descending fibers in self stimulation of the medial forebrain bundle. J Neurosci 6: 919-929 (original) (raw)
Evidence implicating descending fibers in self-stimulation of the medial forebrain bundle
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1986
The role of ascending and descending fibers in self-stimulation of the lateral hypothalamus and ventral tegmental area in the rat was assessed by noting whether anodal hyperpolarization of one of these sites could reduce the rewarding effect of stimulating the other site. Strength-duration curves were obtained by psychophysical means, with one of the depth electrodes serving as the cathode and the other as the anode. It was anticipated that at long pulse durations, conduction in some of the fibers stimulated at the cathode would be blocked at the anode. At shorter durations, the anodal hyperpolarization should have dissipated before the arrival of the action potentials triggered by the cathode. Thus, the predicted effect of the block was to bend the strength-duration curves obtained with two depth electrodes upward at long pulse durations, provided that the anode lay between the cathode and the efferent stages of the pathway responsible for the rewarding effect. To control for possi...
Behavioural Brain Research, 1994
A behavioral version of the collision test was used to determine whether reward-relevant neurons directly link self-stimulation sites in the lateral hypothalamic (LH) and ventral tegmental (VTA) areas. Five male rats served as subjects. Trains of conditioning (C) and test (T) pulses were delivered to the two stimulation sites, each site receiving one of the pulses from each pair. The C-T interval was varied from 0.2-17.3 ms, and the effectiveness of the paired pulse stimulation was estimated by comparing the rate-number curve obtained at each C-T interval to rate-number curves obtained with trains of evenly spaced single pulses delivered via one electrode. For 4 of the subjects, stimulation effectiveness increased with the C-T interval, and the form of this increase was similar regardless of which electrode delivered the C-pulses. These increases in effectiveness are consistent with recovery' from collision block in reward-relevant fibers stimulated at both sites. The domain of the rising portion of the effectiveness versus C-T interval curve spanned 2.2-7.7 ms. Such a gradual rise suggests that the directly stinmlated substrate is composed of fibers with a wide range of conduction velocities and/or refractory periods. The discrepancy between these gradually rising collision curves and the steeply rising curves obtained in previous collision studies may have been due to inadequate sampling of the rate-number function in the earlier studies.
Attenuation of medial forebrain bundle reward by anterior lateral hypothalamic lesions
Behavioural Brain Research, 1996
Psychophysical data consistent with rostro-caudal conduction along reward-relevant neurons linking the lateral hypothalamus (LH) and ventral tegmental area (VTA) have lead to the hypothesis that some of the directly activated neurons responsible for medial forebrain bundle (MFB) self-stimulation arise anterior to the level of the LH. This hypothesis has been challenged on the grounds that lesions to the anterior LH (ALH) often fail to degrade the rewarding value of stimulating more posterior MFB sites. The present study was aimed at investigating the effect of lesion location and stimulation current on the efficacy of ALH lesions in an effort to account for the inconsistencies in the earlier data. Self-stimulation thresholds were obtained for LH and VTA sites by estimating the number of pulses per stimulation train required for half-maximal responding at each of 3 currents. Electrolytic lesions (anodal, 1.0 mA for 10 s) were then made to the ALH at varying medial-lateral coordinates. In 7 of the 14 rats with MFB stimulation sites, lesions to the ALH produced increases in threshold which often declined over the next several days to weeks; in 5 cases thresholds remained elevated by 0.1 to 0.25 loglo units above baseline up to the end of testing. In all but one case, the effective lesions were centered in the lateral ALH. Increases in threshold were more likely to be detected when stimulating at low currents; at low currents fewer neurons are recruited and the lesion can have a greater proportional effect on threshold. These data support the hypothesis that cell bodies, terminals, or fibers of passage in the ALH contribute to the rewarding effect of stimulating more posterior MFB sites.
Role of ipsilateral forebrain in lateral hypothalamic stimulation reward in rats
Physiology & Behavior, 1982
The forebraln was ablated unilaterally to a level dorsal to the thalamus and anterior commissure. Ipsilateral lateral hypothalamic electrodes were then implanted and the animal was tested for self-stimulation behavior. Tests included an initial test for behavioral reactivity to changes in reward level and then two estimates of the quantitative relationships between stimulation parameters: the number-current and charge-duration relationships. Comparison between these findings and those known for intact rats suggest that the substrate for unilateral hypothalamic stimulation reward is not impaired by removal of the ipsilateral tissue.
Brain Research, 1989
Psychophysically derived estimates of recovery from refractoriness were obtained at self-stimulation sites in the lateral hypothalamus and ventral tegmental area. The refractory periods of single units driven by the same stimulation electrodes and stimulation fields were then measured electrophysiologically. Antidromically driven units with refractory periods longer than those of the neurons responsible for the rewarding effect were concentrated in the septal complex. Units with refractory periods that overlapped the estimates for the reward-related neurons were found in this region as well but were also encountered in neighboring structures lateral, ventral, and/or caudal to the septal nuclei. It is argued that this latter class of units should be considered as possible constituents of the directly stimulated substrate for the rewarding effect because they are driven by rewarding stimulation, have refractory periods similar to those of the reward-related neurons and arise in or near regions in which lesions have been effective in decreasing the rewarding effect of stimulating the medial forebrain bundle.
Behavioural Brain Research, 1990
It has been proposed that the directly stimulated axons underlying the rewarding effect of medial forebrain bundle (MFB) stimulation originate in the forebrain and descend at least as far as the ventral tegmentum. However, little is known about the location of the somata that give rise to these axons. Among the nuclei that contribute fibers to the descending component of the MFB and project past the lateral hypothalamus (LH) and ventral tegmental area (VTA) are cell groups within the amygdaloid complex. In this study, the rewarding effectiveness of stimulating the LH and VTA was measured before and after the amygdaloid complex was damaged by electrolytic lesions. Changes in rewarding effectiveness were inferred from shifts in the frequency required to sustain a half-maximal rate of lever-pressing at each of 3 currents. Following the lesions, there was no clear evidence of substantial, sustained decreases in rewarding effectiveness at the 14 stimulation sites, although one subject ceased to self-stimulate reliably. Given that the lesions damaged the principal amygdaloid sources of descending MFB fibers, these results suggest that the amygdaloid complex is not a major source of the directly activated fibers responsible for the rewarding effect of MFB stimulation.
Effects of excitotoxic lesions of the basal forebrain on MFB self-stimulation
Physiology & Behavior, 1996
ARVANITOGIANNIS, A., M. WARACZYNSKI AND P. SHIZGAL. Effects of excitotoxic lesions of the basal forebrain on MFB self-stimulation. PHYSIOL BEHAV 59(4/5) [795][796][797][798][799][800][801][802][803][804][805][806] 1996.--Electrolytic lesions of the anterior medial forebrain bundle (MFB) have been shown to attenuate the rewarding impact of stimulating more caudal MFB sites. In the present study, excitotoxic lesions were employed to determine the relative contribution of somata or fibers of passage contributing to that effect. Changes in reward efficacy were inferred, at three currents, from lateral displacements of the curve relating the rate of responding to the number of stimulation pulses per train. After baseline data were collected from stimulation sites in the lateral hypothalamus (LH) and the ventral tegmental area (VTA), 70 nmol of N-methyl-D-aspartic acid was injected via cannulae aimed at basal forebrain sites. Three subjects were injected with vehicle and served as controls. In 5 out of 15 cases, lesions encompassing the lateral preoptic area, anterior LH, and substantia innominata resulted in long-lasting, large increases (0.2-0.47 log ~0 units) in the number of pulses required to maintain half-maximal rates of self-stimulation for low currents delivered via the LH electrode; smaller increases (0.08-0.33 log10 units) were noted at moderate and high currents. Seven rats with similar or more dorsally located damage showed moderate or transient increases in the number of pulses required to maintain half-maximal rates of LH or VTA self-stimulation. Vehicle injections did not affect behaviour. Varying degrees of demyelination were seen, mostly removed from the electrode tip, and in locations that varied substantially across subjects manifesting similar changes in self-stimulation. These results support the notion that somata in the basal forebrain give rise to some of the directly activated fibers subserving self-stimulation of the MFB. Self-stimulation NMDA Excitotoxic lesions Lateral preoptic area Lateral hypothalamus Ventral tegmental area Rat Substantia innominata ALTHOUGH 40 years have passed since Olds and Milner discovered the phenomenon of brain stimulation reward (BSR), the identity of the directly activated neurons responsible for this striking behavioural phenomenon has yet to be established. Nonetheless, considerable progress has been made toward this end. Psychophysical studies have described physiological and anatomical characteristics of the reward-related neurons directly activated by stimulation of the medial forebrain bundle (MFB) . These studies imply that the directly stimulated MFB substrate includes fine, myelinated fibers coursing through the lateral hypothalamus (LH) and the ventral tegmental area (VTA) (2). In at least some of the directly activated fibers subserving MFB reward, the behaviourally relevant direction of conduction is rostro-caudal . Given what is known about MFB anatomy, this suggests that basal forebrain structures are likely sources of these descending reward-relevant axons. Single-unit recording experiments have identified "candidate" cells in the basal forebrain, cells that are antidromically activated by rewarding MFB stimulation and that exhibit properties matching those derived psychophysically (24,26). However, the profile of candidate neurons is not necessarily unique to those that carry the reward signal. Thus, lesion experiments are invaluable in establishing which candidate neurons compose part of the reward substrate and which merely resemble the reward-related neurons. A decrease in the magnitude of the rewarding effect following damage to a nucleus containing candidate cells provides evidence i Andreas Arvanitogiannis was supported by a scholarship from the Alexander S. Onassis Foundation. The work described here was performed in partial fulfillment of the requirements for his MA degree.
Physiology & Behavior, 1981
SHIZGAL. Refractory periods and anatomical linkage of the substrates for lateral hypothalamic and periaqueductal gray self-stimulation. PHYSIOL. BEHAV. 27(1) [95][96][97][98][99][100][101][102][103][104] 1981.--The pulse-pair technique was employed (a) to investigate the refractory periods of the reward-related neurons activated by lateral hypothalamic (LH) and periaqueductal gray (PAG) stimulation, and (b) to examine whether these two sites are linked by the same reward-related neurons. These properties of the reward substrate were inferred from selfstimulation data. In eight out of ten subjects, recovery from refractoriness began at about the same time at both sites (0.4--0.6 msec). However, the time course of recovery was consistently slower at the PAG placements. A behavioral adaptation of the collision test failed to reveal reward-related fibers that directly link the LH and PAG. Nonetheless, the rewarding effects of stimulation at the two sites summated with roughly 60% efficiency. These data are consistent with the notion that the rewarding effects of LH and PAG stimulation are mediated by different pathways that ultimately converge.
Brain Research, 1989
Electrical self-stimulation in the lateral hypothalamus was recorded in both hemispheres of 20 rats before and after making a lesion either by unilateral radiofrequency stimulation or by injection of N-methyl-D.L-aspartate into the region of the peduncular-pontine nucleus. For the animals which received the radiofrequency lesion, a rate-intensity function was established for 3 stimulation intensities 3 days before and 5 days after the lesion. For the animals in which N-methyl-D.L-aspartate was injected, a reinforcement threshold was measured 3 days before and after the lesion using a psychophysical method-of-limits procedure. With the rate-intensity procedure a decrease in the rate of self-stimulation was observed at the highest stimulation intensity through the electrode situated contralateral to the side of the lesion. Similarly, with the reinforcement threshold method, a significant increase in threshold was found from the electrode placed in the hemisphere contralateral but not ipsilateral to the site of the lesion. These data suggest an involvement of primarily crossed pathways coursing to or from the peduncular-pontine nucleus as being involved in the control of lateral hypothalamic self-stimulation.
Effects of NMDA Lesions of the Medial Basal Forebrain on LH and VTA Self-Stimulation
Physiology & Behavior, 1998
ARVANITOGIANNIS, A., L. RISCALDINO AND P. SHIZGAL. Effects of NMDA lesions of the medial basal forebrain on LH and VTA self-stimulation. PHYSIOL BEHAV 65 (4/5) 805-810, 1999.-Rewarding stimulation of the medial forebrain bundle (MFB) increases Fos-like immunoreactivity in many brain areas, including an ipsilateral, basal forebrain region extending from the medial preoptic area (MPO) to the lateral preoptic area, and substantia innominata. Excitotoxic lesions of the lateral portion of this region have been found to produce large sustained or transient increases in the number of pulses required to maintain half-maximal lever-pressing (required number of pulses) for MFB stimulation. In the present study, changes in self-stimulation of the lateral hypothalamus and ventral tegmental area were assessed following excitotoxic lesions of more medial structures, including the MPO and bed nucleus of the stria terminalis. Increases in the required number of pulses (up to 0.16 log 10 units) were seen in only 2 of 10 subjects. In two other rats, the reward effectiveness of the stimulation was moderately increased after the lesion as manifested in decreases of up to 0.14 log 10 units in the required number. No appreciable change from baseline was seen in the remaining six subjects. The simplest interpretation of these results is that neurons with cell bodies in the medial portion of the basal forebrain may make a smaller contribution to the rewarding effect of MFB stimulation than neurons in the lateral portion. © 1999 Elsevier Science Inc.
Physiology & Behavior
ARVANITOGIANNIS, A., L. RISCALDINO AND P. SHIZGAL. Effects of NMDA lesions of the medial basal forebrain on LH and VTA self-stimulation. PHYSIOL BEHAV 65 (4/5) 805-810, 1999.-Rewarding stimulation of the medial forebrain bundle (MFB) increases Fos-like immunoreactivity in many brain areas, including an ipsilateral, basal forebrain region extending from the medial preoptic area (MPO) to the lateral preoptic area, and substantia innominata. Excitotoxic lesions of the lateral portion of this region have been found to produce large sustained or transient increases in the number of pulses required to maintain half-maximal lever-pressing (required number of pulses) for MFB stimulation. In the present study, changes in self-stimulation of the lateral hypothalamus and ventral tegmental area were assessed following excitotoxic lesions of more medial structures, including the MPO and bed nucleus of the stria terminalis. Increases in the required number of pulses (up to 0.16 log 10 units) were seen in only 2 of 10 subjects. In two other rats, the reward effectiveness of the stimulation was moderately increased after the lesion as manifested in decreases of up to 0.14 log 10 units in the required number. No appreciable change from baseline was seen in the remaining six subjects. The simplest interpretation of these results is that neurons with cell bodies in the medial portion of the basal forebrain may make a smaller contribution to the rewarding effect of MFB stimulation than neurons in the lateral portion. © 1999 Elsevier Science Inc.
A portrait of the substrate for self-stimulation
Psychological Review, 1981
Quantitative properties of the neural system mediating the rewarding and priming effects of medial forebrain bundle (MFB) stimulation in the rat have been determined by experiments that trade one parameter of the electrical stimulus against another. The first-order neurons in this substrate are for the most part long, thin, myelinated axons, coursing in the MFB and ventral tegmentum, with absolute refractory periods in the range .5-1.2 msec and conduction velocities of 2-8 m/sec. Local potentials in these axons decay with a time constant of about .1 msec. A supernormal period follows the recovery from refractoriness. These axons integrate current over exceptionally long intervals, accommodate slowly, and fire on the break of prolonged anodal pulses. These properties rule out the hypothesis that catecholamine pathways constitute the first-order axons. The second-order (postsynaptic) part of the substrate shows surprisingly simple spatial and temporal integrating characteristics. We examine the logic that permits conclusions of this sort to be derived from behavioral data and the role of these derivations in establishing neurobehavioral linkage hypotheses.
Brain Research, 2000
Prior studies indicate that lesioning the retrorubral fields (RRF) decreases the rewarding effect of medial forebrain bundle (MFB) stimulation, although these studies did not make the RRF their primary target. This study directly investigates the role of the RRF in MFB self-stimulation using transient lidocaine-induced inactivation of target tissue rather than permanent lesioning. In 18 rats with MFB stimulation electrodes, inactivation of the RRF via 0.5 and 1.0 ml of 4% lidocaine produced immediate, substantial upward shifts in the frequency required to maintain half-maximal self-stimulation response rates whereas injecting comparable volumes of saline did not. Bilateral inactivation was particularly effective, especially at medium and high stimulation currents, although unilateral inactivation ipsilateral to the stimulation site was also effective. Contralateral inactivation alone did not substantially change the stimulation's reward value, although contralateral inactivation appeared to contribute to the effectiveness of bilateral inactivation. The frequency required to maintain half-maximal responding returned to baseline levels by 15-20 min after lidocaine infusion. In seven rats whose infusion sites were not in the RRF, lidocaine inactivation did not consistently degrade the stimulation's reward value. These results indicate that some neural elements located in the RRF contribute to the rewarding effect of MFB stimulation. Possible roles for these elements in the anatomical substrate for MFB self-stimulation are discussed.
Neurophysiological analysis of brain-stimulation reward in the monkey
Brain Research, 1980
Neuronal activity related to brain-stimulation reward and to feeding was analyzed in rhesus monkeys and squirrel monkeys as follows. First, self-stimulation of the lateral hypothalamus, orbitofrontal cortex, amygdala and nucleus accumbens was found. Second, a population of single neurones in the lateral hypothalamus was found to be trans-synaptically activated from one or several self-stimulation sites. It was also found that populations of neurones in the orbitofrontal cortex and amygdala were activated from at least some of the self-stimulation sites. Thus, in the monkey, there is evidence for an interconnected set of self-stimulation sites, stimulation in any one of which may activate neurones in the other regions. These sites include the lateral hypothalamus, amygdala, and orbitofrontal cortex. Third, in one sample of 764 neurones in the lateral hypothalamus and substantia innominata which were activated from brainstimulation reward sites, 13.6 ~ were also activated during feeding, by the sight and/or taste of food. The responses of the neurones with activity associated with taste occurred only while some substances (e.g. sweet substances such as glucose) were in the mouth, depended on the concentration of the substances being tasted, and were independent of mouth movements made by the monkeys. Fourth, the responses of these neurones occurred to food when the monkeys were hungry, but not when they were satiated. Fifth, self-stimulation occurred in the region of these neurones in the lateral hypothalamus and substantia innominata, and was attenuated by satiety. These results suggest that self-stimulation of some brain sites occurs because of activation of neurones in the lateral hypothalamus and substantia innominata activated by the sight
Behavioural Brain Research, 1990
Microinjections of the muscarinic antagonist, atropine, of dopamine, or of the local anesthetic, procaine, in the ventral tegmentum elevated frequency thresholds for lateral hypothalamic self-stimulation. The largest and most robust effects were observed following atropine (30 or 60 #g) microinjections. The most sensitive sites for the atropine effect were near dopamine cells. In order to determine if the effects of atropine can be reversed by pretreatment with a cholinergic agonist, carbachol (1-3 #g) was microinjected 15 min prior to atropine. Carbachol pretreatment attenuated the frequency threshold elevation of atropine by 47-95 Yo. Since atropine is a local anesthetic, the effects of procaine on self-stimulation thresholds were tested as well. Procaine (100 or 250 #g) in ventral tegmentum elevated frequency thresholds by much less than atropine. Therefore, while atropine attenuates reward primarily through blockade of muscarinic receptors, the local anesthetic effect of atropine may enhance the threshold elevation. Dopamine (1-10 #g) also elevated frequency thresholds, but when dopamine injections were repeated daily, the threshold elevations were attenuated. This attenuation contrasted with the robust effects of atropine, and may reflect the development of autoreceptor subsensitivity. Hence, both dopaminergic and muscarinic receptors in ventral tegrnentum are involved in lateral hypothalamic brain stimulation reward. * S.M. McGlynn published formerly under the name of S. Whitfield.
Evidence for a role of the preoptic area in lateral hypothalamic self-stimulation
Brain Research, 1985
We examined the effects of unilateral radiofrequency lesions in the preoptic area on lateral hypothalamic self-stimulation in 15 rats. The animals were tested for self-stimulation in the lateral hypothalamus at 3 different current intensities from electrodes placed in both hemispheres, and then received a unilateral lesion in the preoptic area. Four hours later they were again tested for self-stimulation at the 3 current intensities and then daily over the following 14 days~ or until they recovered their presurgicai rates of self-stimulation. Rate of self-stimulation decreased in the damaged hemisphere, and recovered to prelesion levels within 2 weeks in 6 of 9 rats. In the intact hemisphere rate of self-stimulation increased above the prelesion level during a period from 1 to 2 weeks after the lesion. These results su~test that the preoptic area is involved in lateral hypothalamic self-stimulation. The effects of D-amphetamine (1 mg/kg) and apomorphine (2 mg/kg) injections on turning behaviorwere also studied in an open field and in a rotometer. Apomorphine induced contraversive turning to the lesion side in the open field and o-amphetamine induced ipsiversive turning in the rotometer.