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PubMed1990

Stimulation of the subcallosal fornix excites neurones in the cat preoptic region which project to the medial basal hypothalamus and in the medial forebrain bundle.

The projection of neurones in the cat preoptic region driven by stimulation of the subcallosal fornix was systematically explored. We found 19% projected to the medial basal hypothalamus (MBH) and 10% projected in the medial forebrain bundle (MFB). Neurones projecting to the MBH were driven more often by stimulation of the lateral aspect of the fornix than the medial aspect (P = 0.006) and these neurones were thought to lie in the medial division of the preoptic nucleus (MPNm) since they were found significantly more often in the medial 0.6 mm of the preoptic region than more laterally (P = 0.028). A reverse projection from the preoptic region in the fornix is also suggested based on the finding of 24 antidromically activated neurones in the preoptic region following stimulation of the fornix.

Animals↗
PubMed1981

The role of the medial forebrain bundle in the mediation of the hypothalamic-hypophyseal-adrenal responses to acute neurogenic stress.

Adult male rats, intact (N) or bearing bilateral lesions in the medial forebrain bundle (MFB), were acutely exposed to visual, audiogenic, or thermal stress, during the following which serum ACTH and corticosterone (CS) levels were determined. The marked elevations in serum concentrations of both ACTH and CS which occurred in intact animals following photic stimulation were absent in MFB rats. The normal ACTH and CS responses to audiogenic stress were slightly delayed and attenuated, respectively, in the operated group, whereas the responses of both hormones to exposure to elevated environmental temperature were partially blocked in lesioned, as compared to intact, animals. These results demonstrate that the MFB is involved in mediating the ACTH, as well as the CS secretory responses to acute stress exposure. More specifically, the role of the MFB, vís-à-vis the hypothalamo-hypophyseal-adrenal axis, appears to be in the transmission of sensory input from rostral brain areas posteriorly.

Adrenocorticotropic Hormone↗
PubMed1991

Medial forebrain bundle units in the rat: dependence of refractory period estimates on pulse duration.

The slope of some psychophysically-derived curves describing recovery from refractoriness in medial forebrain bundle (MFB) reward neurons decreases as the pulse duration is lengthened. This effect has been attributed to increased recruitment of small-diameter fibers by the long-duration pulses. Alternatively, this effect might be due to increases in the refractory periods of a fixed population of neurons. By means of extracellular recording, we measured the effect of increasing the pulse duration on recovery from refractoriness in 26 neurons antidromically activated by MFB stimulation. In all cases, recovery from refractoriness was delayed as the pulse duration was increased from 0.1 ms to 2.0 ms. The delay was more pronounced at near-threshold currents than at higher currents and was generally largest in neurons that recovered most rapidly from refractoriness when stimulated with brief pulses. These effects of long duration pulses on recovery of excitability in a fixed population of neurons may have contributed to the delay in recovery implied by the psychophysical data. Thus, delayed recovery does not necessarily imply preferential recruitment of small-diameter fibers by the long-duration pulses.

Animals↗
PubMed1988

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.

Animals↗
PubMed1990

The distribution of changes in local cerebral energy metabolism associated with brain stimulation reward to the medial forebrain bundle of the rat.

Using the quantitative 2-[14C]deoxyglucose autoradiographic method, local rates of glucose utilization were measured in rats during brain stimulation reward to the medial forebrain bundle. Metabolic activation was observed both rostral and caudal to the site of stimulation. These sites included the nucleus accumbens, olfactory tubercle, lateral septum, and ventral tegmental area. In many cases, increases in glucose utilization occurred bilaterally. These data suggest the involvement of both ascending and descending systems in brain stimulation reward. Furthermore, despite the unilateral nature of the electrical stimulation, increases in glucose utilization were observed both ipsilateral and contralateral to the site of stimulation.

Animals↗
PubMed1997

Increased expression of NGFI-A mRNA in the rat striatum following burst stimulation of the medial forebrain bundle.

Using in situ hybridization, we examined the mRNA expression for several immediate early genes in dopamine-innervated brain areas following electrical burst vs. regular stimulation of the medial forebrain bundle in anaesthetized rats. Two hours after 5 Hz burst stimulation, the expression of the nerve growth factor-inducible clone A (NGFI-A) mRNA was increased in the medial part of the striatum. This increase was prevented by pretreatment with the dopamine-D1 receptor antagonist, SCH23390 (0.1 mg/kg i.p.). After 8 Hz burst stimulation, NGFI-A mRNA expression was increased in the medial, central and lateral parts of the striatum. Induction occurred predominantly in cells expressing mRNAs for the dopamine-D1 receptor, substance P and dopamine and cAMP-regulated phosphoprotein (DARP-32). Regular stimulation had no effect on NGFI-A mRNA expression. The induction of NGFI-A was related to the levels of dopamine released by burst or regular stimulation as demonstrated with in vivo amperometry. Two hours after stimulation, the expression of none of the other genes studied was altered. One hour after 8 Hz burst stimulation, the expression of NGFI-A, NGFI-B and jun-B mRNAs was increased in the striatum and that of NGFI-A, NGFI-B, c-fos, fos-B and jun-B mRNAs was variably increased in the nucleus accumbens and lateral septum. These results provide additional support for the physiological importance of burst firing activity in midbrain dopamine neurons for the activation of their target cells. They demonstrate a spatial and temporal specificity as regards the brain region, the gene activated, the receptor involved and the phenotype of the cells affected.

Animals↗
PubMed2006

Pathological dynamics of activated microglia following medial forebrain bundle transection.

To elucidate the role and pathological dynamics of activated microglia, this study assessed the phagocytic, immunophenotypic, morphological, and migratory properties of activated microglia in the medial forebrain bundle (MFB) axotomized rat brain. Activated microglia were identified using two different monoclonal antibodies: ED1 for phagocytic activity and OX6 for major histocompatibility complex (MHC) class II. Phagocytic microglia, characterized by ED1-immunoreactivity or ED1- and OX6-immunoreactivity, appeared in the MFB and substantia nigra (SN) as early as 1-3 days post-lesion (dpl), when there was no apparent loss of SN dopamine (DA) neurons. Thereafter, a great number of activated microglia selectively adhered to degenerating axons, dendrites and DA neuronal somas of the SN. This was followed by significant loss of these fibers and nigral DA neurons. Activation of microglia into phagocytic stage was most pronounced between 14 approximately 28 dpl and gradually subsided, but phagocytic microglia persisted until 70 dpl, the last time point examined. ED1 expression preceded MHC II expression in phagocytic microglia. All phagocytic microglia sticking to DA neurons showed activated but ramified form with enlarged somas and thickened processes. They were recruited to the SNc from cranial, dorsal and ventral aspects along various structures and finally stuck to DA neurons of the SNc. Characteristic rod-shaped microglia in the white matter were thought to migrate a long distance. The present study strongly suggests that neurons undergoing delayed neurodegeneration may be phagocytosed by numerous phagocytic, ramified microglia at various sites where specific surface signals are exposed or diffusible molecules are released.

Animals↗
PubMed2004

Histological, behavioural and neurochemical evaluation of medial forebrain bundle and striatal 6-OHDA lesions as rat models of Parkinson's disease.

We compared the effect of an injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB) and into the striatum on different parameters for evaluation of motor dysfunction and dopamine denervation in rats, as a function of time. A combination of behavioural, neurochemical and histological techniques was employed. Amphetamine-induced rotation is shown to provide a first rough estimation of motor impairment. Indeed, the number of rotations observed after amphetamine administration can distinguish between a partial and a near complete (>90%) denervation in the substantia nigra. However, lesion sizes of 50-80% resulted in similar rotational behaviour. Similarly, the elevated body swing test (EBST) can determine severe lesions, but is not sensitive enough in the partial model. In both models, determination of the dopamine tissue content with HPLC is a more precise measure of striatal dopamine innervation than striatal TH-immunostaining. The number of cells estimated by TH- and Nissl-staining correlated well in the striatal model, but there was a discrepancy between both measures in the MFB-lesioned animals. Therefore, additional Nissl-staining is necessary for better estimation of the size of the lesion at the level of the substantia nigra or ventral tegmental area in the severely lesioned animals. The MFB lesion model mimics end-stage Parkinson's disease. The striatal injection of 6-OHDA described here cannot be considered a progressive model, since there was no change in the number of TH-immunoreactive cells in the substantia nigra up to 8 weeks post-lesioning. However, the partial denervation renders its quite suitable for mimicking early stage Parkinson's disease, and is thus suitable for testing possible neuroprotective and neurotrophic drugs.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2006

Role of alpha(1)-adrenoceptors of the locus coeruleus in self-stimulation of the medial forebrain bundle.

The present experiments were undertaken to clarify the role of central alpha(1)-adrenoceptors in reward processes. Rats, trained to self-stimulate via electrodes in the medial forebrain bundle of the lateral hypothalamus, were administered alpha(1)-selective drugs near the locus coeruleus (LC), a site of a dense concentration of alpha(1)-receptors. Effects on reward potency were assessed from shifts in rate-frequency curves while effects on motor response capacity were judged from changes in the maximal rates of responding. It was found that local blockade of LC alpha(1)-receptors with terazosin produced a significant dose-dependent and site-dependent rightward shift of 0.08 log units and a significant decrease of 16.3% in the maximum response rate. Both effects were completely reversed by coadministration of the alpha(1)-agonist, phenylephrine and were not attributable to terazosin's weak action at alpha(2)-adrenoceptors. It is concluded that LC alpha(1)-adrenoceptors are involved both in reward/motivational processes and operant response elaboration which are postulated to work together to facilitate goal attainment.

Adrenergic alpha-Agonists↗
PubMed1983

Effects of neonatal destruction of the medial forebrain bundle in the cat: long-term neurochemical, locomotor, and regulatory deficits.

Neonatal kittens (N = 27) 11 to 22 days of age received bilateral electrolytic lesions of the medial forebrain bundle (MFB). These lesions transected the rostral course of the nigrostriatal tract, disrupted other fiber tracts that constitute the MFB, damaged the indigenous neurons of the lateral hypothalamic region, and interrupted striatal output pathways. The behavioral development of these animals was assessed and compared with that of intact littermates (N = 37) and a group of littermates that received lesions that did not encroach upon the MFB (control lesions, N = 16). The MFB lesions produced transient periods of decreased body weight gains. Animals with large MFB lesions had to be tube fed for various periods. Decreased ponderal weight in animals with large MFB lesions occurred throughout the duration of their survival (1 to 2 years of age). Development of locomotor activity was assessed in an open field. At about 6 weeks of age animals with MFB lesions became hyperactive compared with their intact littermates and this hyperactivity was still apparent at 6 months of age when testing was discontinued. Caudate dopamine and tyrosine hydroxylase were measured after the animals were killed. Large MFB lesions produced a marked decrease in concentrations of caudate dopamine (75%) and the activity of tyrosine hydroxylase (62%). These results indicate that early postnatal damage to the MFB in cats produces a constellation of behavioral deficits that differ both quantitatively and qualitatively from the effects of similar lesions produced in the adult animal.

Animals↗
PubMed1980

Ascending components of the medial forebrain bundle from the lower brain stem in the rat, with special reference to raphe and catecholamine cell groups. A study by the HRP method.

The afferent connection of the medial forebrain bundle (MFB) arising from the lower brain stem have been investigated by means of horseradish peroxidase (HRP) with sensitive substrate, the injection was made iontophoretically into MFB at various levels. After injection of HRP into MFB, a significant number of HRP-labeled neurons were observed in the following structures of the lower brain stem: (1) raphe nuclear group, (2) locus coeruleus, (3) n. laterodorsalis tegmenti, (4) parabrachial area, (5) A1, A2, A4, A5 and A7 areas where noradrenaline-containing neurons were disseminated, (6) A8, A9 and A10 areas which contain dopamine neurons, (7) surrounding area of the fasciculus longitudinalis medialis at the level of the n. propositus hypoglossi, (8) n. prepositus hypoglossi and (9) mesencephalic gray matter. As a rule, the ascending projections are ipsilateral and course in the medial part of MFB. Regarding the raphe nuclei, we have demonstrated that the caudal raphe nuclei, such as n. raphe magnus and obscurus (but not n. raphe pallidus), also send their axons to the hypothalamus. Particularly, the axons of n. raphe magnus ascend in MFB to reach the level of the preoptic or anterior septal areas. Furthermore, in accordance with previous reports, HRP-labeled cells were also identified in the n. raphe dorsalis, centralis superior and pontis, respectively. It should be further noted that labeled cells appeared in the n. linearis caudalis. In addition, the present study indicates a number of non-aminergic cell groups as sources of ascending mfb fibers. On the whole, the present study further clarified the organization of the components of the MFB ascending from the lower brain stem, and provided some additional anatomical substrates for the physiology of the control of the forebrain by the lower brain stem neurons.

3,3'-Diaminobenzidine↗
PubMed1979

Synaptosomal uptake of hypothalamic monoamines and recovery of pituitary-adrenal activity following medial forebrain bundle lesions in rats.

The normal diurnal variation in plasma corticosterone (COR) was abolished and the response to ether stress was enhanced at 3 days following the production of medial forebrain bundle (MFB) lesions in male rats. However, by 7 days following surgery, basal plasma COR levels and the response to ether stress appeared normal. These alterations and subsequent recovery of pituitary-adrenal activity were accompanied by decreasing hypothalamic synaptosomal uptake of serotonin (5HT) and increasing synaptosomal uptake of dopamine (DA), evident at 3 and continuing at 7 days following the lesion. Uptake of norepinephrine (NE) was not affected at 3 days but showed a reduction at 7 days following surgery. The results suggest that disruption of ascending 5HT and NE fibers to the hypothalamus can alter pituitary-adrenal activity but that normal activity recovers by 7 days following the lesion. The correlation between recovery of pituitary-adrenal activity and increases in the normal uptake of hypothalamic DA suggest that DA may interact with 5HT and NE systems in the normal control of adrenocorticotrophin (ACTH) release.

Animals↗
PubMed1984

Adrenocortical responses to ether stress and neural stimuli in rats following the injection of 6-hydroxydopamine into the medial forebrain bundle.

Adrenocortical responses, as expressed by changes in plasma corticosterone concentrations, after ether stress, or photic, acoustic, or sciatic nerve stimulation were studied in rats, with 6-hydroxydopamine or vehicle injected into the medial forebrain bundle (MFB). The neurotoxin partially inhibited the response to photic stimulation only, indicating the involvement of MFB catecholaminergic fibers in the transmission of this response which stimulates adrenocortical secretion.

Acoustic Stimulation↗
PubMed1992

Effects of frequency and pattern of medial forebrain bundle stimulation on caudate dialysate dopamine and serotonin.

In vivo microdialysis was employed to detect changes in extracellular dopamine and serotonin in the rat caudate in response to electrical stimulation of the medial forebrain bundle. Extracellular dopamine concentrations increased linearly as a function of the frequency (4-33 Hz) of evenly spaced stimuli in both the presence and absence of cocaine added to the dialysate. Because dopamine neurons are known to fire in single-spike and burst patterns, stimulation pulses were also delivered in a bursting pattern. The response of extracellular dopamine was augmented in both the presence and absence of cocaine when the same number of stimuli were delivered in bursts as compared to an evenly spaced pattern. Serotonin, which was only assessed in the presence of cocaine, similarly increased linearly with frequency, but, in contrast to the dopamine response, levels of serotonin were not augmented by stimuli presented in bursts. These results suggest that microdialysis can be used to detect physiological changes in synaptic transmitter concentrations.

Animals↗
PubMed1988

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.

Animals↗
PubMed1983

Effects of neonatal destruction of the medial forebrain bundle in the cat: long-term disturbances in learning ability, response to amphetamine challenge, and reactivity to auditory stimuli.

These experiments ascertain some of the long-term behavioral effects of neonatal medial forebrain bundle (MFB) lesions in the cat. Bilateral electrolytic lesions (N = 27) were made when the animals were 11 to 22 days of age. The long-term behavioral development of cats with these lesions were compared with that of a group of intact littermates (N = 37) and a group of littermates that received lesions that did not encroach upon the MFB. When the animals were 18 to 40 days of age they were tested in a spatial discrimination. Animals with bilateral MFB lesions were capable of learning the discrimination but made more repeated errors than animals in the other groups. This effect was compensated for with additional training. When tested on a visual discrimination at 3 to 4 months of age, kittens with MFB lesions learned the discrimination in a normal manner. When the discrimination cues were reversed, however, they responded more frequently to the previously reinforced cue. The effects of d-amphetamine were assessed when animals were 7 to 12 months of age. Animals with bilateral MFB lesions displayed less frequent and intense head movement stereotypies and more locomotor responses to amphetamine than animals in other groups. The reactivity to a series of auditory stimuli was assessed when the animals were 1 to 2 years of age. Neonatal MFB lesions produced an impaired pattern of habituation of reactivity to auditory stimuli. Cats with these lesions responded normally to the initial presentations of the vocalizations. However, 24 h later they responded to the stimuli more vigorously than animals in the other groups. Taken together the results of this experiment and the previous report indicate that some effects of neonatal MFB damage were qualitatively different from those of lesions inflicted in mature animals and that a complex interaction among a number of factors was probably responsible for these differences.

Acoustic Stimulation↗
PubMed1979

Light and electron microscopic studies on the medial forebrain bundle in the rat. I. Nerve terminals in the lateral hypothalamus of extrahypothalamic origin.

Degenerated nerve terminals were demonstrated in the lateral hypothalamus of the rat following transection of the rostral and caudal fibres to the medial forebrain bundle (MFB) and a parasagittal cut along the lateral edge of the hypothalamus. In the light of these findings the termination of extrahypothalamic MFB pathways on intrinsic neurons is assumed.

Animals↗