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M M Behbehani

Publications and source records attributed to M M Behbehani.

At least 55 records · Page 3Linked to original sources
PubMed1990

A double-labeling method for AChE and fluorescent retrograde tracers.

Staining for the degradative enzyme acetylcholinesterase (AChE) is an important tool in studying central cholinergic/cholinoceptive systems. AChE staining has also been useful in identifying the projections of AChE-containing neurons and codistribution of AChE with other neurotransmitters. The intensity and opacity of conventional AChE histochemical reaction products, however, pose problems for such double-labeling studies. Here, we have successfully combined a modified version (37) of the Koelle-Friedenwald AChE reaction with retrograde transport of the fluorescent tracer, Fluoro-Gold (FG). By omitting the final intensification steps of the Koelle-Friedenwald reaction, a translucent, light-stable reaction product is created. Viewed under darkfield illumination, this precipitate is of similar intensity and sensitivity to that produced by conventional AChE histochemical processing. Prior administration of an AChE-inhibitor yields preferential staining of AChE-positive neuronal somata. This nonintensified darkfield AChE (NIDA) histochemical method was compatible with visualization of retrogradely transported FG in AChE-positive neurons, allowing unambiguous identification of the projections of AChE-containing neurons.

Acetylcholinesterase↗
PubMed1989

Acetylcholinesterase and Nissl staining in the same histological section.

Acetylcholinesterase (AChE) enzyme histochemistry and Nissl staining are commonly utilized in neural architectonic studies. However, the opaque reaction deposit produced by the most commonly used AChE histochemical methods is not compatible with satisfactory Nissl staining. As a result, precise correlation of AChE and Nissl staining necessitates time-consuming comparisons of adjacent sections which may have differential shrinkage. Here, we have modified the Koelle-Friedenwald histochemical reaction for AChE by omitting the final intensification steps. The modified reaction yields a non-opaque reaction product that is selectively visualized by darkfield illumination. This non-intensified darkfield AChE (NIDA) reaction allows clear visualization of Nissl staining in the same histological section. This combined AChE-Nissl method greatly facilitates detailed correlation of enzyme and cytoarchitectonic organization.

Acetylcholinesterase↗
PubMed1988

Nucleus cuneiformis and pain modulation: anatomy and behavioral pharmacology.

The anatomical substrate and behavioral pharmacology of stimulation-produced analgesia resulting from electrical stimulation of the pontomesencephalic nucleus cuneiformis (NCF) was determined in the present study. Maximum increase in nociceptive tail-flick latencies following NCF stimulation occurred during the first 5 min post stimulation and decreased afterwards. The increased reflex latency could be attenuated by prior treatment with the narcotic antagonist, naloxone or the cholinergic antagonist, scopolamine. The anatomical projections of NCF were identified in autoradiographic and histochemical studies. Ipsilateral fibers coursed caudal from the NCF injection site through the ventral pontine reticular formation to innervate nucleus raphe magnus and the ipsilateral nucleus magnocellularis. At rostral medullary levels fibers coursed dorsolateral to innervate the ipsilateral nucleus reticularis parvocellularis. Descending contralateral fibers crossed through the decussation of the superior cerebellar peduncle, then coursed ventrolaterally projecting to the contralateral nucleus magnocellularis. Two primary groups of ascending fibers were observed. The dorsally located group ascended through the central tegmental tract projecting to the dorsal raphe, ipsilateral periaqueductal gray, nucleus parafascicularis and centromedianus, the intermediolateral and lateral thalamic nuclei. The ventral group coursed ventrolateral from the injection site projecting to the substantia nigra, zona compacta, ventral tegmental area of Tsai, zona incerta, Fields of Forel, lateral hypothalamic nucleus and nucleus reuniens. These anatomic and behavioral data suggest that NCF plays an important role in sensory/motor integration relevant to pain transmission.

Amino Acids↗
PubMed1988

Interactions between the lateral hypothalamus and the periaqueductal gray.

Anatomical and physiological experiments were conducted to characterize the interactions between the lateral hypothalamus (LH) and the periaqueductal gray (PAG) and to determine the role of neurotensin in their interaction. Anatomical studies using injection of Phaseolus vulgaris leucoagglutinin into the LH showed an extensive projection to the ventromedial and the ventrolateral PAG and a less dense projection to the medial and dorsal parts of this region. Physiological experiments were performed on both deeply and lightly anesthetized animals. Electrical stimulation of the LH caused excitation of PAG cells with an onset latency of approximately 14 msec. There was a strong correlation between the response of PAG cells to electrical stimulation and injection of glutamic acid into the LH. Electrical or chemical stimulation of the LH produced an increase in tail flick latency in the lightly anesthetized animals that outlasted the stimulation period. There was a strong correlation between the response of PAG cells to electrical and chemical stimulation of the LH and their response to pressure-injected neurotensin. It is concluded that an excitatory projection from the LH to PAG exists which may involve neurotensin. This pathway may be involved in the analgesia produced by LH stimulation.

Animals↗
PubMed1987

Heterogeneous distribution of neurotensin-like immunoreactive neurons and fibers in the midbrain periaqueductal gray of the rat.

The midbrain periaqueductal gray (PAG) has been shown to be a site where various manipulations induce pain suppression. Recent physiological evidence (Behbehani and Pert, 1984; Behbehani et al., 1987) suggests that neurotensin has pronounced physiological actions in PAG and effects pain suppression. We have performed immunohistochemical studies in order to determine the magnitude and distribution of neurotensin-like immunoreactive (NT-IR) cell bodies and fibers in PAG. NT-IR cell bodies were common throughout PAG, although there were more in the caudal than the rostral half. NT-IR neurons were much more numerous in the ventral than the dorsal half of PAG, and some appeared to be located within the dorsal raphe nucleus. The pattern of NT-IR fibers was analyzed with the aid of image enhancement/analysis and densitometry. The fibers were found to be heterogeneously distributed, being most heavily concentrated in the region adjacent to the cerebral aqueduct in the caudal two-thirds of PAG. The distribution of NT fibers closely matches sites where exogenously applied NT elicits long-lasting excitation of PAG neurons (Behbehani et al., 1987). Based on the known physiological and behavioral actions of NT in PAG, the present anatomical results suggest that NT acts on elements located predominantly in the medial and ventrolateral parts of PAG. Neurons activated by NT may project directly to the nucleus raphe magnus and adjacent ventral medulla (Behbehani and Pert, 1984) to activate neurons that project to the spinal cord and modulate nociceptive circuits.

Animals↗
PubMed1987

Effect of neurotensin on neurons in the periaqueductal gray: an in vitro study.

The effect of neurotensin (NT) on periaqueductal gray (PAG) neurons was measured with extra- and intracellular recording methods in an in vitro preparation. Neurons excited by NT were heterogeneously distributed, being preferentially located in a region of PAG rich in NT-like fiber immunoreactivity. The majority of the responsive neurons were located in regions surrounding the aqueduct and the medial part of PAG. In 90% of the neurons, application of NT produced excitation that lasted for more than 2 min, while in the remaining cells, the excitatory effect lasted for less than 1 min. An inhibitory action of NT was rarely observed. Intracellular recordings showed that NT produced a depolarization leading to an increase in the spontaneous activity and multiple spiking with only a slight decrease in membrane resistance. The excitatory effect of NT was observed in neurons that were maintained in a solution containing cobalt. These results support the hypothesis that NT action on PAG neurons is due to the depolarization of the membrane and that this effect is mediated through a postsynaptic mechanism.

Action Potentials↗
PubMed1986

Response of nucleus raphe magnus neurons to electrical stimulation of nucleus cuneiformis: role of acetylcholine.

There is considerable evidence that cells in the ventral medulla which includes nucleus raphe magnus (NRM) and nucleus magnocellularis are involved in a descending pain inhibitory system. Anatomical studies indicate a strong projection from nucleus cuneiformis (NCF) to the ventral medulla and histochemical studies suggest that many NCF neurons are cholinergic. Therefore, we investigated the effect of NCF stimulation on NRM unit activity and explored the possible role of acetylcholine (ACh) in this interaction. Of 180 NRM neurons examined, 43% were excited and 14% were inhibited by NCF stimulation. The average latency to the peak excitatory response was about 14 ms with a range of 5-32 ms. There was a tendency for the response latencies to cluster around 5 and 14 ms. Inhibitory responses were between 10 and 65 ms in duration. The anatomical specificity of the effective stimulation site was assessed by determining the response of a given NRM neuron to stimulation of areas dorsal and ventral as well as within NCF. The most reliable and intense responses of NRM neurons was observed with electrode placements within NCF. The most effective NCF region for activating NRM neurons corresponded to that region of NCF that contains a large population of neurons that project directly to NRM as seen in the present histochemical studies. The involvement of ACh in the interaction between NCF and NRM was examined with iontophoretic application of ACh and its antagonists. Of NRM neurons that responded to ACh, 79% were excited, an effect which was blocked by scopolamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1986

Cardiovascular toxicity of local anesthetics: an alternative hypothesis.

The current study examined the possibility that high local anesthetic concentrations within the central nervous system could contribute to the toxic cardiovascular effects observed clinically after an accidental intravenous injection. Equal numbers of molecules of lidocaine (1.6 microliter of a 2% solution) and bupivacaine (1.0 microliter of a 4% solution) were injected at three vasomotor and cardioactive areas in the rat medulla by means of a 28-gauge hypodermic needle and a microsyringe. These areas were the C1 region, the intermediolateral column (IML), and the nucleus tractus solitarius (NTS). Both lidocaine and bupivacaine at C1 significantly decreased mean arterial pressure and, at IML, resulted in significant bradycardia and hypotension. At NTS, both lidocaine and bupivacaine caused significant bradycardia and hypotension, which were accompanied by ventricular arrhythmias in 55% of the animals. In all animals in whom ventricular arrhythmias were associated with lidocaine, the arrhythmias spontaneously reverted to normal sinus rhythm. In 50% of animals developing ventricular arrhythmias after bupivacaine, the arrhythmias resulted in death. Using an equal number of molecules of lidocaine and bupivacaine, all three regions studied demonstrated that bupivacaine was 2-4 times more potent than lidocaine in producing cardiovascular effects. These data demonstrate that direct application of local anesthetics within the medullary region of the central nervous system can result in hypotension, bradycardia, and ventricular arrhythmias similar to what may be seen in humans after accidental intravenous injections of local anesthetics. Moreover, the sites and mechanisms of action appear to be identical for bupivacaine and lidocaine. Thus bupivacaine does not appear to be an aberrant local anesthetic, as some have suggested, but rather produces more profound effects related to its potency and physicochemical properties.

Animals↗
PubMed1984

A mechanism for the analgesic effect of neurotensin as revealed by behavioral and electrophysiological techniques.

Behavioral and electrophysiological techniques were used to examine the effects of local injections of neurotensin (NT) into the periaqueductal gray (PAG). The results of the behavioral experiments showed that injection of NT into the PAG produced dose-dependent analgesia that lasted for as long as 60 min and was not blocked by naloxone. However, electrolytic lesions of the nucleus raphe magnus (NRM) and its surrounding area, abolished the analgesic effect of NT. Electrophysiological experiments indicated that micro-pressure application of NT onto neurons in the PAG had a predominantly excitatory effect. Furthermore, it was shown that injection of NT into the PAG produced excitation of the NRM neurons. It is concluded that NT produces its analgesic effect by excitation of PAG neurons which leads to activation of the pain inhibitory system that originates from the NRM and its surrounding areas in the medulla.

Analgesics↗
PubMed1984

Afferent projections to the nucleus cuneiformis in the rat.

Afferent projections to the nucleus cuneiformis (CNF) were examined in the rat with retrograde tracing techniques employing microinjection of wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP). As the CNF is an extensive nucleus in its rostrocaudal extent, the rostral and caudal subdivisions of the CNF were studied separately. Projections to caudal CNF were observed from all subdivisions of the periaqueductal gray, the deep layers of the superior colliculus as well as the caudal levels of the CNF. In contrast, WGA-HRP microinjections into the rostral CNF retrogradely labeled more cells but they were located exclusively in the rostral CNF. The present data support the hypothesis that three adjacent brain stem nuclei, i.e. the caudal CNF, the periaqueductal gray and the deep layers of the superior colliculus, function in unison to control ventral medullary pain pathways. The relationship of these three structures to the rostral CNF is unclear and deserves further study.

Animals↗
PubMed1984

Ascending and descending projections from nucleus reticularis magnocellularis and nucleus reticularis gigantocellularis: an autoradiographic and horseradish peroxidase study in the rat.

The projections of the rostral medulla were studied using retrograde and orthograde transport techniques in the rat. The present horseradish peroxidase (HRP) studies indicate that the ventral portion of nucleus reticularis gigantocellularis (NGC) and nucleus reticularis magnocellularis (NMC) project to both rostral and caudal levels of the spinal cord, while dorsal NGC projects only to the rostral cord. A differential density distribution of labeled cells was observed, with the greatest density of NGC-spinal neurons located rostral to the level of the inferior olive; and the greatest density of NMC-spinal neurons located caudally. This differential density distribution, when coupled with microiontophoretic application of [3H]amino acids allowed relatively independent labeling of the adjacent NGC- and NMC-spinal systems. On the basis of the HRP and autoradiographic studies 3 separate regions were delineated: dorsal NGC, ventral NGC and NMC. Descending projections from NGC were observed to the lateral vestibular nucleus, facial nucleus, hypoglossal nucleus and nucleus cuneatus. At cervical levels NGC fibers projected through the ventral and ventrolateral columns. Terminal fields were observed in laminae VII, VIII and to a lesser extent in IX. Labeled NGC fibers became difficult to follow by thoracic levels, which is consistent with the present HRP results. A continuum of descending NGC projections was observed with dorsally located NGC neurons projecting bilaterally through the ventral columns, and ventrally located NGC cells projecting through the ipsilateral ventrolateral columns. Ascending projections from NGC to the motor nucleus of V, trochlear nucleus, oculomotor nucleus, Edinger-Westphal nucleus, the ventral aspect of the periaqueductal gray, the deep and intermediate layers of the superior colliculus, nucleus parafasicularis and centromedianus, the Fields of Forel and the dorsal and lateral hypothalamic nuclei were observed. Descending projections from NMC to the dorsal nucleus of the vagus, hypoglossal nucleus, nucleus commissuralis and intercalatus were observed. At cervical levels, fibers project through the ipsilateral lateral columns, particularly its dorsal aspect. Terminal fields are located ipsilaterally in laminae IV, V and VI, and bilaterally in VII, VIII and X. NMC projections continue through caudal levels of the spinal cord including a projection to the ipsilateral intermediolateral columns. Ascending NMC projections are limited to the ventral pontine reticular formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

Susceptibility of feline spinal cord energy metabolism to severe incomplete ischemia.

Feline spinal cords were subjected to 10 to 30 minutes of severe incomplete ischemia (average reduction in blood flow of 92%) with and without 90 minutes of recirculation, and the L-2 segment was analyzed for high-energy phosphates and certain glycolytic metabolites. Spinal cord tissue lactic acid levels were stepwise elevated, and adenosine triphosphate (ATP), phosphocreatine (P-creatine), and glucose were progressively consumed by increasing durations of ischemia. However, upon restoration of blood flow, there was extensive recovery of energy metabolites and normalized lactic acid, demonstrating resumption of mitochondrial oxidative metabolism. These data indicate that the spinal cord can tolerate at least 30 minutes of severely reduced blood flow before recovery of energy metabolism is significantly impaired upon restitution of blood flow.

Adenosine Triphosphate↗
PubMed1982

The role of acetylcholine in the function of the nucleus raphe magnus and in the interaction of this nucleus with the periaqueductal gray.

The nucleus raphe magnus (NRM) plays an important role in the inhibition of pain. Although this region receives afferents from several areas of the brain, the afferent input from the periaqueductal gray (PAG) has been shown to have significant physiological importance. Together, these two sites constitute the major component of a descending network involved in pain inhibition. In this study the role of acetylcholine (ACh) in the function of the NRM was investigated and the possibility that ACh may be a transmitter between the PAG and the NRM was tested. ACh was applied iontophoretically. Scopolamine and gallamine were used to test the type of cholinergic receptors that are present in the NRM. The results of this study shows the following. (1) The majority of the cells in the NRM are excited by ACh. (2) This response to ACh is partially or totally blocked by scopolamine whereas gallamine does not block the response. (3) There is no correlation between the excitatory response to stimulation of PAG and to ACh. There are cells that respond to PAG stimulation by inhibition but are excited by ACh and there are a few cells that are inhibited by ACh but are excited by PAG stimulation. (4) Scopolamine, at a dose that blocks the ACh response, does not block the response to PAG stimulation. (5) There is no correlation between the response to ACh and the type of projection (direct or indirect) to the spinal cord, as tested by stimulation of the dorsolateral funiculus. From these results it is concluded that ACh is an excitatory transmitter at the NRM region but this transmitter does not mediate the interaction between the PAG and NRM.

Acetylcholine↗
PubMed1981

Interaction between central gray and nucleus raphe magnus: role of norepinephrine.

Recordings were made from single cells in the nucleus raphe magnus (NRM) of the rat. The response of these cells to electrical stimulation of the periaqueductal gray (PAG) was correlated with their response to iontophoretically applied norepinephrine (NE). It is shown that NE can cause excitation as well as inhibition of NRM neurons, although excitatory response was obtained more often than an inhibitory response. No correlation between the response to PAG stimulation and to NE was obtained. It is concluded that NE is not the transmitter that mediates the interaction between the PAG and NRM.

Animals↗