Interhemispheric involvement of the anterior cortical nuclei of the amygdala in rewarding brain stimulation

The amygdaloid complex is one of the structures thought to modulate brain stimulation reward (BSR) elicited from the median forebrain bundle (MFB). Previous metabolic and behavioral data from our laboratory point to the amygdaloid cortical nuclei as key to this process. In this study, thresholds for rewarding stimulation of the MFB were determined for 42 days, 21 days following an electrolytic lesion to amygdaloid nuclei ipsilateral to the stimulation electrode, and 21 days following one applied to the contralateral amygdala. A subset of animals showed post-lesion changes in MFB frequency thresholds that were maintained if not augmented after the second lesion. These ranged from 26% to 150% compared to baseline values, among the largest ever reported to our knowledge. Interestingly, damage to anterior sites within the cortical nuclei was the most effective in producing modifications to the rewarding value of the stimulation. Equally singular was the finding that contralateral lesions tended to alter thresholds more than ipsilateral ones, confirming our earlier finding of interhemispheric connectivity in amygdaloid modulation of MFB reward signals. This interpretation was substantiated by tracking long-term metabolic activity in the amygdala using cytochrome oxidase histochemistry. The density of reaction product at damaged amygdala sites was negatively correlated (r=-0.90) with the increases in thresholds obtained at contralateral MFB loci. Together with the fact that such large lesion effects are seldom obtained, our metabolic results point to the existence of a relationship between these nuclei and reward signals generated at the MFB. Moreover, our data suggest that this communication takes place interhemispherically.     

Mesencephalic substrate of reward: lesion effects

Psychophysical studies suggest that reward-relevant neurons in the posterior mesencephalon (PM) form a caudal extension of the axonal pathway that mediates the rewarding effectiveness of electrical stimulation of the medial forebrain bundle. The present study sought to further characterize the reward-relevant functional link between these two regions by assessing changes to the rewarding effectiveness of caudal medial forebrain bundle stimulation (ventral tegmental area, VTA) subsequent to electrolytic lesions of different PM sites. A total of 13 rats were tested, 11 of these at bilateral VTA stimulation sites. Overall, rewarding effectiveness was reduced in five rats and pontentiated in four. The presence and magnitude of the effects were site-, current- and time-dependent, and ranged from 0.1 to 0.4 log(10) unit shifts in reward magnitude, with most effects falling below 0.3 log(10) units. Generally, these effects became apparent approximately two weeks after the lesion. In addition to these effects, PM lesions placed on or close to the midline also produced small transient reductions in rewarding effectiveness immediately after the lesion, an effect that disappeared within three days. Conversely, lateral PM lesions were associated either with no immediate effects or with small transient potentiations of reward. The finding that lesions of the PM placed on the midline, just off the midline or laterally all altered the rewarding effectiveness of VTA stimulation suggests that the reward-relevant circuitry is distributed diffusely throughout the PM.     

Electrophysiological characteristics of neurons in forebrain regions implicated in self-stimulation of the medial forebrain bundle in the rat

In an attempt to identify neurons likely to play a role in self-stimulation of the medial forebrain bundle (MFB), action potentials of single neurons in the septum and basal forebrain of anesthetized rats were recorded by means of extracellular electrodes. Refractory period estimates were obtained from cells antidromically activated by stimulation of the lateral hypothalamus or ventral tegmental area, and estimates of interelectrode conduction time were obtained from cells that were driven by stimulation of both sites. The results show that some descending MFB axons arising in the medial septum, diagonal band of Broca and neighboring forebrain structures have characteristics comparable to properties of MFB reward neurons inferred from behavioral experiments.     

Comparisons of connectivity and conduction velocities for medial forebrain bundle fibers subserving stimulation-induced feeding and brain stimulation reward

A behavioral adaptation of the paired-pulse collision technique was used to determine whether the same medial forebrain bundle (MFB) fibers of passage mediate brain stimulation reward (BSR) and stimulation-induced feeding (SIF) induced by lateral hypothalamic and ventral tegmental electrical stimulation. Step-functions relating second-pulse effectiveness to interpulse interval suggested connectivity between the directly activated SIF fibers at these two stimulation sites were seen in 4 animals; these data indicate that SIF, like BSR, is mediated, at least in part, by long-axon MFB fibers. In the two animals that could be tested in both paradigms, similar effects were seen in BSR tests; this suggests that either the same fibers or fibers with remarkably similar conduction velocities and medial-lateral and dorsal-ventral alignment contribute to the two behaviors.     

Effects of periaqueductal gray stimulation on diencephalic neural activity

The effects of ventral tegmental area of Tsai (VTA) stimulation on lateral hypothalamic (LH), lateral preoptic area (LPA), and medial hypothalamic neuronal activity were determined in anesthetized rats. Recordings from 81 hypothalamic neurons indicate that stimulation produces predominantly decreases in hypothalamic neuron activity. Increases in activity due to VTA stimulation occurred less frequently. Following single rectangular pulse stimulation, 0.5 msec, 0–500 μA, short latency decreases in activity occurred. Longer latency increases in discharge frequency were also observed. Dose response relations were established for 56% of the LH neurons, 78% of the LPA neurons, and for 82% of the medial hypothalamic neurons following VTA stimulation. Decreases and in a few cases increases in activity seemed to involve only one or two synapses. Antidromic responses verified interconnections between the VTA and the hypothalamus and revealed relatively slow conduction velocities of 0.45 and 0.81 m/sec. The changes in discharge frequency which occurred following VTA stimulation were similar in direction to the effects of the direct microiontophoretic application of dopamine (DA) or norepinephrine (NE). Since DA increased or decreased while NE decreased discharge frequency, these microiontophoretic tests indicated that the shorter latency VTA stimulation induced increases and decreases in neural activity were associated with VTA dopaminergic neuron stimulation and that in some cases short and long latency decreases in neuronal activity were due to activation of VTA ventral bundle NE fibers of passage or to indirect polysynaptic mechanisms. Results demonstrate the interconnections between various regions of the hypothalamus and the VTA along the extent of the medial forebrain bundle (MFB). The cross-validation of neuroanatomical and various electrophysiological metods in establishing the nature of hypothalamic connections was discussed.     

Lesions of midline midbrain structures leave medial forebrain bundle self-stimulation intact.

Previous work with psychophysically-based collision methods and pharmacological manipulation suggests a role in medial forebrain bundle (MFB) self-stimulation for neurons lying along the midline between the cerebral hemispheres, in the mid- and/or hindbrain. Also, recently-proposed models of the anatomical substrate for medial forebrain bundle stimulation reward suggest that at least part of the directly-activated axons of this substrate arise from mid- and/or hindbrain somata, bifurcate, and send bilateral projections to the MFB of each hemisphere. Branches of these axons are thought to cross the midline at some point near the ventral tegmental area. This study examines the effects on MFB stimulation reward of lesioning midbrain structures that lie along the midline between hemispheres. In 13 rats, lesions of the median raphe, the decussation of the superior cerebellar peduncle, or the interpeduncular nucleus were all ineffective in altering the stimulation frequency required to maintain half-maximal levels of operant responding for stimulation reward. These results are discussed in terms of implications for recent models of the anatomical substrate for brain stimulation reward.     

Cholinergic and catecholaminergic afferents to the olfactory bulb in the hamster: a neuroanatomical, biochemical, and histochemical investigation

A series of neuroanatomical, biochemical, and histochemical studies have been conducted to determine the sources of cholinergic afferents to the main olfactory bulb (MOB) in the hamster. Following horseradish peroxidase (HRP) injections that are restricted to the MOB, retrograde neuronal labeling is observed bilaterally in the anterior olfactory nucleus, locus coeruleus, and raphe nuclei, and ipsilaterally in the ventral hippocampal rudiment, dorsal peduncular cortex, piriform cortex, nucleus of the lateral olfactory tract, anterior pole of the medial septal area and vertical limb of the diagonal band, nucleus of the horizontal limb of the diagonal band (HDB), and hypothalamus. Spread of HRP into the accessory olfactory bulb results in additional neuronal labeling ipsilaterally in the bed nucleus of the accessory olfactory tract, medial amygdaloid nucleus, and bed nucleus of the stria terminalis, and bilaterally in the posteromedial cortical amygdaloid nucleus. Retrograde tracing studies also have been conducted in cases with lesions in the basal forebrain or hypothalamus to assess the extent to which such lesions interrupt fibers of passage from other sources of centrifugal afferents, and the effects of such lesions on choline acetyltransferase (CAT) activity and catecholamine content in the MOB and on acetylcholinesterase (AChE) activity in the forebrain have been evaluated. Lesions in the basal forebrain reduce or eliminate CAT and AChE activity in the MOB in direct relationship to the extent of damage to the HDB. Norepinephrine (NE) content in the MOB also is reduced by basal forebrain lesions, but in relationship to damage of the medial forebrain bundle (MFB). The hypothalamic lesions have no effect on AChE activity in the forebrain or on CAT activity in the MOB, but they eliminate retrograde labeling in the locus coeruleus and raphe nuclei and reduce the NE content of the MOB to undetectable levels. The dopamine content of the MOB is not reduced by any of the lesions. Anterograde tracing studies have been conducted to compare the rostral projection patterns of the HDB with the distribution of AChE activity. Most of the rostrally directed axons travel in association with the MFB. A small component of axons travels in association with the lateral olfactory tract. Within the MOB, the axons terminate predominantly in the glomerular layer and in the vicinity of the internal plexiform layer. The projection and termination patterns of the HDB correspond well with the distribution of AChE activity. These various results indicate that the HDB is the major source of cholinergic afferents to the MOB.     

Lesions of pontomesencephalic cholinergic nuclei do not substantially disrupt the reward value of medial forebrain bundle stimulation

This study examines the effects of lesioning the pedunculopontine tegmentum (PPTg) and laterodorsal tegmentum (LDTg) on the reward effectiveness of medial forebrain bundle (MFB) stimulation. Although the focus is on the effects of unilateral lesions made ipsilateral to stimulation sites in the hypothalamic and ventral tegmental MFB, the effects of contralateral lesions of both targets are also investigated. Reward effectiveness was assessed using the rate–frequency curve shift paradigm. In nine rats with unilateral PPTg lesions and five rats with unilateral LDTg lesions, the frequency required to maintain half-maximal response rats was generally not changed by more than 0.1 log units relative to prelesion baseline mean. In three rats with contralateral PPTg lesions and four rats with contralateral LDTg lesions, required frequency was also not substantially changed. The results are interpreted in terms of a previously proposed hypothesis regarding the role in MFB self-stimulation of ascending cholinergic input from the pontomesencephalon to ventral tegmental dopaminergic neurons.     

Responses of ventral tegmental area GABA neurons to brain stimulation reward

Dopamine neurons in the ventral tegmental area (VTA) have been implicated in rewarded behaviors, including intracranial self-stimulation (ICSS). We demonstrate, in unrestrained rats, that the discharge activity of a homogeneous population of presumed VTA GABA neurons, implicated in cortical arousal, increases before ICSS of the medial forebrain bundle (MFB). These findings suggest that VTA GABA neurons may be involved in the attentive processes related to brain stimulation reward (BSR).     

Temporary inactivation of the retrorubral fields decreases the rewarding effect of medial forebrain bundle stimulation

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 microl 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.     

Opposite medial thalamic unit responses to rewarding and aversive brain stimulation

Medial thalamus receives fibers from both medial forebrain bundle (MFB) and hindbrain and midbrain reticular formation (RET). The MFB and RET stimulations are rewarding and aversive respectively. In 32 unanesthetized cerveau isolé rats, 158 units were recorded. The MFB and RET effects converge on two thirds of the units recorded in the dorsal medial and paracentral nuclei of thalamus and are opposite in the following ways: post-stimulus pattern of unit discharge during 7 Hz stimulation; slow-wave recruiting with MFB, but not RET, 7 Hz stimulation; and at a “desynchronization” stimulus frequency (20 Hz), MFB elicits decreased unit discharge and RET elicits increased unit discharge, compared to the 7 Hz rates. In the intralaminar and parafasicular nuclei, post-train (60 Hz, 0.2 sec) decreases and increases in unit firing lasting seconds are often elicited with MFB and RET trains respectively. Stimulation of hypothalamic sites outside MFB did not elicit these MFB effects; parafasicular stimulation did not elicit the RET effects. The MFB effects were not seen in habenula or ventral basal thalamus. Hippocampal, habenular, and ventral medial thalamic units did not show opposite MFB and RET effects. Threshold currents for the opposite MFB and RET effects are similar to those eliciting self-stimulation and escape respectively in several operated rats tested both behaviorally and neurophysiologically.     

Forebrain neurons driven by rewarding stimulation of the medial forebrain bundle in the rat: comparison of psychophysical and electrophysiological estimates of refractory periods

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.     

Forebrain origins and terminations of the medial forebrain bundle metabolically activated by rewarding stimulation or by reward-blocking doses of pimozide

Using [14C]-2-deoxyglucose autoradiography, we determined which forebrain and diencephalic areas showed metabolic alterations in response to unilateral electrical stimulation of the posterior medial forebrain bundle at parameters chosen to produce a just-submaximal rewarding effect. At these parameters, only a few areas were activated. There was no detectable activation anterior or dorsal to the genu of the corpus callosum. Just anterior to the anterior commissure, there was strong activation of the vertical limb of the diagonal band of Broca, with a focus in the nucleus of the diagonal band. Just posterior to the anterior commissure, there was strong activation of compartment "c" of the medial forebrain bundle (MFB), with weaker activation of the bed nucleus of the stria terminalis and the medial preoptic area. At midhypothalamic levels, the dorsolateral, dorsomedial, and ventral MFB all showed activation. There was bilateral suppression of activity in the lateral habenula. Activation appeared to end in the anterior ventral tegmental area of Tsai. Reward-blocking doses of the neuroleptic pimozide activated the caudate and the lateral habenula but did not alter any of the unilateral effects of stimulation. Using longer pulse durations and/or shifting the site of stimulation to the substantia nigra activated many of the systems not activated in the first experiment, including all of the major dopaminergic projection systems, proving the capacity of the technique to reveal activation of these systems. The results permit one to define a discrete projection system that merits electrophysiological investigation as a likely substrate for the rewarding effect of MFB stimulation. They also suggest that dopaminergic projection systems may not form part of the reward pathway itself.     

Comparisons of refractory periods for medial forebrain bundle fibers subserving stimulation-induced feeding and brain stimulation reward: a psychophysical study

Paired-pulse stimulation techniques were used to infer distributions of refractory periods (RPs) for the directly activated medial forebrain bundle (MFB) substrates of brain stimulation reward (BSR) and stimulation-induced feeding (SIF). Each RP distribution suggested (a) a subpopulation of contributing fibers with refractory periods between 0.4 and 0.6 ms, (b) absence of significant numbers of fibers with refractory periods between 0.6 and 0.7 ms, and (c) a second subpopulation (or set of overlapping subpopulations) with refractory periods between 0.7 and 1.5-2.5 ms. Similar RP estimates were obtained in different animals, despite the fact that stimulation sites ranged from the anterior lateral hypothalamus to the ventral tegmental area; this finding is consistent with the view that the directly activated substrate of both behaviors involves MFB fibers of passage. While the possibility cannot be ruled out that the two behaviors result from activation of distinct sets of fibers with remarkably similar refractory periods, the more likely possibility is that a common--or at least partially common--MFB substrate underlies brain stimulation reward and stimulation-induced feeding.     

Identification of the hypothalamic site through which locus coeruleus axons decussate to reach and stimulate contralateral LH-RH neurons

Recently we reported that locus coeruleus (LC) electrical stimulation (ES) amplifies the quantity of LH released prior medial preoptic nucleus (MPN)-electrochemical stimulation (ECS). In these studies we also observed that amplification of LH release occurred only when we activated those LC neurons whose cell bodies reside contralateral to the site of MPN-ECS. Seemingly, stimulatory LC axons decussate to reach contralateral hypothalamic regions which contain LH-RH neurons. The purpose of the present study was to identify the site(s) at which such decussation(s) occur. To accomplish this we used a special knife blade to make gross transections in hypothalamic regions previously described by others as regions where LC decussations occur. Transection 1 (TI) interrupted axons coursing through the medial forebrain bundle (MFB) in the region of the posterior lateral hypothalamus. This transsection was placed ipsilateral to the side of LC-ES and it had no effect on LH patterns of concentrations which were released by MPN-ECS. However, T1 completely blocked the amplifying effects of LC stimulation on LH secretion after MPN-ECS. Transection 2 (T2) was placed in the region of the MPN, parallel to the superior sagittal sinus. The knife blade was lowered in midline to the top of the 3rd ventricle and transected all fibers which cross midline within and around the anterior commissure. LH release following MPN-ECS was not appreciably affected in these rats nor did T2 alter the amplifying effects of LC-ES on LH. However, while plasma LH peaked between 60 and 75 min and then declined towards baseline in MPN + LC-stimulated rats, it remained significantly elevated throughout the remainder of the blood collection periods (180 min) in rats receiving combined MPN + LC and T2. Transection 3 (T3) also was placed in the MPN region and differed from T2 only in that we lowered the knife to the base of sphenoid bone. Thus, T3 disrupted all fibers which cross midline in the AC region and dorsal to the optic chiiasm (dorsal supraotic decussation of LC axons). This transection did not affect LH release evoked by MPN-ECS but completely eliminated the amplifying effects of LC stimulation after MPN-ECS on LH secretion. These data indicate that stimulatory LC axons which affect LH-RH neuronal activity enter the hypothalamus ipsilateral to the site of LC-ES and then project rostrally in the MFB to the lateral preoptic area. In this region, certain stimulatory LC fibers leave the MFB and cross midline in the dorsal supraoptic decussation to reach the contralateral MPN where they affect LH-RH neuronal activity. The data obtained in rats with AC transections (T2) also suggest that inhibitory inputs from extrahypothalamic regions enter the hypothalamus and suppress or arrest LH-RH release. Disruption of these inhibitory preoptic projections results in the sustained secretion of elevated levels of LH-RH/LH following MPN + LC stimulation.     

Histamine synthesizing afferents within the amygdaloid complex and bed nucleus of the stria terminalis of the rat.

The regional distribution of histidine decarboxylase (HD) activity has been studied in the amygdaloid complex and the bed nucleus of the stria terminalis (BST) of the rat. The central and medial nuclei of the amygdala had 2-fold higher HD activity levels than the remaining nuclei of the complex. HD activity was exceptionally high in the BST, particularly in its ventral part. A lesion of the stria terminalis had no effect on this distribution whereas a combined lesion of the stria terminalis and the so-called ventral pathway induced a decrease of approximately 60% in all the amygdaloid nuclei, but not in the BST. On the other hand, a lesion of the medial forebrain bundle (MFB) induced a similar decrease in both the amygdaloid nuclei and the BST. These results confirm that HD-containing fibres are present in the MFB. On the one hand these project massively to the BST and on the other penetrate in the amygdala ventromedially along the ansa peduncularis and preferentially innervate the more medially located nuclei.     

Comparison of Intracranial Self-Stimulation Evoked From Lateral Hypothalamus and Ventral Tegmentum: Analysis Based on Stimulation Parameters and Behavioural Response Characteristics

The comparison of intracranial self-stimulation (ICSS) derived across the anteroposterior axis of medial forebrain bundle (MFB) from the anterior border of lateral hypothalamus (LH) to the ventral mesencephalon including ventral tegmental area-substantia nigra (VTA-SN) in Wistar rats was assessed through stimulation parameters and behavioural response characteristics. The interpretation of response rate/charge consumption (μC/min) with respect to rectangular wave and sine wave electrical stimulation parameters suggests that the rectangular wave parameters are better in order to get the maximum responding rates. The most vigorous and robust responding was observed in the VTA or VTA-SN boundary placements, followed by placements in medial sector of LH. The acquisition of ICSS was fastest in the case of VTA-stimulation. The next site with respect to rapidity of ICSS was posterio-ventral LH. The extinction curves indicated that it is faster and exponential in case of VTA-SN, but it is slower with longer duration in case of LH-MFB. ICSS of SN were accompanied by exploratory locomotion and head bobbing. Thirty-one percent subjects with SN/VTA stimulation showed rotational behaviour. Seventy-eight percent of subjects with LH stimulations showed stimulus-bound ejaculations. Thirty-two percent of subjects with posterior LH stimulations showed biting of pedal edges. LH stimulations were accompanied by induced seizures and increased grooming in 18% and 13% of subjects, respectively. There was lateralisation of cerebral hemispheric function as right paw preference was noted in majority of rats, whether sites of stimulation were in the left or right cerebral hemisphere. The various other modes of pedal pressing operants like use of paw and mouth, alternate paw dribbling, use of head electrode assembly to manipulate the pedal were also recorded and analysed. Copyright © 1996 Elsevier Science Inc.     

The role of the dopaminergic projections in MFB self-stimulation

Psychophysical experiments indicate that the first stage of the reward pathway in medial forebrain bundle self-stimulation consists of small myelinated descending axons. Pharmacological experiments show that neuroleptics attenuate or abolish the rewarding effect. This had led to the hypothesis that the descending myelinated axons synapse on an ascending dopaminergic second stage projection. 2-Deoxy-[14C]glucose autoradiography in self-stimulating animals or animals receiving automatically administered rewarding stimulation after treatment with reward-blocking doses of pimozide reveals activation of a descending myelinated system but no stimulation-produced activation of an ascending dopaminergic projection system, even though the autoradiographic method reveals the mild elevations and depressions of activity in dopaminergic terminal fields consequent upon injections of neuroleptics and amphetamine, respectively, and the strong activation of the nigrostriatal projection produced by stimulating directly in the substantia nigra. When the effects of neuroleptics and clonidine are measured by the psychophysical method (that is, by lateral shifts in the rate-frequency function), it is found that both drugs produce only gradual and rather small attenuations of rewarding efficacy up to doses at which it is no longer possible to measure their effects. It is suggested that, for neuroleptics at least, the rewarding effect abruptly fails at these doses. It is further suggested that these drugs do not act on the rewarding pathway itself, but on the process by which the rewarding signal is converted to an enduring rewarding effect.     

Competence of nerve tissue as distal insert promoting nerve regeneration in a silicone chamber

In some medial forebrain bundle (MFB) sites, self-stimulation is often modulated by hunger or satiety. With electrodes in the nucleus accumbens (NAC) such modulation rarely occurs. The influence of food deprivation on MFB self-stimulation is the main basis for the hypothesis that electrical stimulation of the MFB can mimic the rewarding effect of food for hungry animals. To investigate this hypothesis, unit activity was recorded from the lateral hypothalamic area (LHA) of freely moving rats during rewarding stimulation at loci in both MFB and NAC, and during food ingestion. Of 63 neurons tested during MFB stimulation, 41 were inhibited, 19 were activated, and 3 were not influenced. NAC stimulation suppressed 8 of the 31 neurons tested, excited 16, and elicited no response in the remaining 7. During ingestion, 29 of the 63 neurons tested were inhibited and one was facilitated. Of 29 neurons suppressed by food, 20 were also inhibited by rewarding MFB stimulation, but 10 of 13 neurons inhibited by food were excited by rewarding NAC stimulation. Thus, most LHA neurons inhibited during feeding were also inhibited by rewarding MFB stimulation. Rewarding NAC stimulation, however, does not inhibit most LHA neurons that are inhibited by food. This result suggests that LHA neurons which are inhibited by food might be involved in mediation of the rewarding effect of electrical stimulation at some sites in the MFB. Nevertheless, self-stimulation may occur by activating reward processes other than those related to food, because rewarding NAC stimulation does not inhibit LHA neurons which are suppressed by food.     

Evidence implicating descending fibers in self-stimulation of the medial forebrain bundle

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 possible differences in the density of the reward substrate in the lateral hypothalamic and ventral tegmental areas, the strength-duration curves obtained with a given cathode and a depth anode were compared to curves obtained with the same cathode but with an anode consisting of a set of skull screws. It was expected that the concentrated current entering from the depth anode would much more effectively block conduction in the medial forebrain bundle than the diffuse current entering from the large, distant skull screws. The predicted change in the shape of the strength-duration curves was observed only when the ventral tegmental electrode served as the anode and the lateral hypothalamic electrode as the cathode. This is consistent with the notion that in at least some of the neurons responsible for the rewarding effect, action potentials elicited by the lateral hypothalamic electrode had to pass through the ventral tegmental area in order to reach the efferent stages of the reward pathway. In the simplest anatomical arrangement consonant with this view, the somata of these cells lie in the forebrain and give rise to descending axons. As a test of the hypothesis that anodal block was responsible for changing the shape of the strength-duration curve obtained with the ventral tegmental anode, a psychophysical version of the collision test was used to determine whether the tips of the lateral hypothalamic and ventral tegmental electrodes were indeed linked by a common set of reward-related fibers.(ABSTRACT TRUNCATED AT 400 WORDS)