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M M Behbehani

Publications and source records attributed to M M Behbehani.

At least 37 records · Page 2Linked to original sources
PubMed1994

Preoptic projections to Barrington's nucleus and the pericoerulear region: architecture and terminal organization.

The medial preoptic area (MPO), a sexually dimorphic region, plays a pivotal role in neuroendocrine function and reproductive behavior. We recently reported that MPO projects heavily to the midbrain periaqueductal gray (PAG). We also noted that MPO projects to the dorsolateral pontine tegmentum. Here we identified the cells of origin of the MPO-->tegmental projection and delineated the terminal organization of MPO projections to Barrington's nucleus, locus coeruleus (LC), and the rostromedial pericoerulear region (pLCrm). Correlative cyto- and chemoarchitectonic studies were done to define better the nuclear groups of the dorsolateral pontine tegmentum. Retrograde tracing revealed that MPO neurons projecting to the dorsolateral pontine tegmentum are preferentially distributed in distinct subregions of MPO, including the sexually dimorphic medial preoptic nucleus (MPN). Anterograde tracing with wheat germ agglutinin-horseradish peroxidase or Phaseolus vulgaris leucoagglutinin demonstrated considerable target specificity in projections from MPO to the dorsolateral pontine tegmentum. Barrington's nucleus receives a dense focal input along its entire rostrocaudal axis. In addition, pLCrm is heavily targeted by MPO inputs; pLCrm contains a concentrated plexus of extranuclear dendrites of LC neurons. The lateral dorsal tegmental (LDT) nucleus and LC proper receive only sparse input from MPO. MPO projections to Barrington's nucleus could regulate micturition reflexes during reproductive behavior. The MPO-->pLCrm projection could influence noradrenergic LC neurons in relation to reproductive and/or gonadal steroid function. Given the strong established connections from olfactory structures to MPO, it is possible that the MPO-->LC pathway provides an anatomical substrate for olfactory modulation of arousal.

Animals↗
PubMed1994

Characterization of the effect of cholecystokinin (CCK) on neurons in the periaqueductal gray of the rat: immunocytochemical and in vivo and in vitro electrophysiological studies.

The periaqueductal gray (PAG) is an important integration site for pain, autonomic functions, vocalization, fear and anxiety. Cholecystokinin (CCK) is a major neurotransmitter in the PAG and CCK receptors are heterogeneously distributed within the PAG. Since CCK antagonists are anxiolytic and potentiate morphine analgesia, it is possible that these effects of CCK are mediated through alteration of neuronal activities in the PAG. The goals of this study were to examine the anatomical and physiological properties of the PAG CCK containing systems. The distribution of CCK-containing axons and boutons in PAG was examined using immunohistochemical procedures. These studies show that CCK-like immunoreactive (CCK-LIR) fibers and terminals are present throughout PAG, but are particularly heavily concentrated in a focal column that runs longitudinally throughout the rostrocaudal axis of dorsolateral PAG and in nucleus cuneiformis which represents a caudolateral extension of PAG. The physiological effects of CCK on PAG neurons were examined in both in vivo and in vitro preparations. In the in vivo experiments multibarreled electrodes were used to record from PAG neurons and to apply CCK and the CCK antagonists, CR1409 and proglumide. Of 37 neurons recorded in vivo, CCK caused excitation in 25 cells, inhibited 7 cells and had no effect on 5 cells. The excitatory effect was blocked by CR1409 in 11/11 cells tested. Proglumide blocked the excitatory response of CCK in 12/14 cells. Proglumide blocked the inhibitory effect in 2 of 7 cells, but CR1409 had no effect on CCK-evoked inhibition in 7 cells tested. Extracellular, conventional intracellular and whole cell patch clamping procedures were used to study CCK actions in the in vitro slice preparation. In the extracellular recording experiments, responses of PAG cells to CCK were measured in slices that were maintained at 22 degrees C (room temperature) and at 32 degrees C. CCK excited 40/56, inhibited 7/56 and had no effect on 9/56 cells; excitatory responses were blocked by CR1409 in 32/36 cells and by proglumide in 25/27 cells tested. Inhibitory responses to CCK were unaffected by CR1409, but were blocked in 3/7 cells by proglumide. Conventional intracellular recordings were made from 13 cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Evidence for GABAB-mediated inhibition of transmission from the olfactory nerve to mitral cells in the rat olfactory bulb.

The GABAB agonist baclofen blocks transmission from the olfactory nerve to second order neurons in the frog olfactory bulb, and GABAB receptors in the rat olfactory bulb are selectively located in the glomerular layer. A reasonable hypothesis, therefore, is that inhibition in the glomerular layer is mediated, at least in part, by GABAB receptors. Here, we investigated the role of GABAB receptors in regulating the responses of mitral cells to activation of the olfactory nerve in the rat. Topical application of baclofen to the surface of the rat olfactory bulb reduced the amplitude of field potentials evoked by olfactory nerve stimulation (orthodromic response). Baclofen reduced the orthodromic response in a dose-dependent manner but the drug had no effect on the field potential evoked by antidromic activation of mitral cell axons (antidromic response). Baclofen also reduced olfactory nerve-evoked responses of mitral cells in an olfactory bulb slice preparation. The pharmacological specificity of the inhibition was confirmed by showing that the GABAB antagonist, CGP 55845A, blocked the inhibitory action of baclofen. These results suggest that transmission from olfactory nerve terminals to second order neurons is negatively regulated by periglomerular GABAergic interneurons; this inhibition is mediated, at least partially, by GABAB receptors.

Animals↗
PubMed1994

The neurophysiologic mechanisms of tourniquet pain. The activity of neurons in the rostroventral medulla in the rat.

BACKGROUND: Tourniquet pain frequently complicates the use of pneumatic tourniquets during surgical procedures involving the extremities. The mechanisms of tourniquet pain are not understood and therefore the treatment is nonspecific. An animal model was sought to provide an ethical means to study the neurophysiologic and neuropharmacologic mechanisms of tourniquet pain. Neurons in the rostral ventromedial medulla are involved in the nociceptive-and circulatory-responsive neuronal networks. The goal of this study was to determine the activity of neurons in the rostral ventromedial medulla in response to the maintenance of tourniquet inflation in the rat as a component of an investigation of the neurophysiologic mechanisms of tourniquet-induced pain. METHODS: In 18 male, pentobarbital-anesthetized rats, heart rate, systolic blood pressure (SBP), and cell firing rates (CFR) of nociceptive-responsive rostral ventromedial medulla neurons, characterized as having an OFF or ON cell response to noxious heat, were monitored. CFR was monitored continuously at baseline, during an IV infusion of phenylephrine sufficient to increase SBP by 50%, during the application of a pneumatic tourniquet to the hind limb thigh and inflated to 300 mmHg for a period of 60 min, and during a 30-min recovery period. RESULTS: Phenylephrine-induced hypertension resulted in an increase in OFF CFR. Maintenance of tourniquet inflation resulted in a progressive decrease in OFF CFR and a progressive increase in ON CFR. An increase in SBP in response to tourniquet pain paralleled the changes in CFR. Mean SBP at 5 min preinflation, 5 min postinflation, 55 min postinflation, and 10 min postdeflation were 101 +/- 11, 103 +/- 9, 118 +/- 14, and 103 +/- 12 mmHg, respectively. CONCLUSIONS: The changes in SBP and CFR observed during tourniquet inflation were consistent with previously reported responses to nociceptive stimuli. Phenylephrine-induced hypertension caused an opposite effect on the CFR of rostral ventromedial medulla neurons as compared with a noxious stimulus such as heat or maintenance of tourniquet inflation. This experimental design is presented as an animal model to study the neurophysiologic and neuropharmacologic aspects of tourniquet pain.

Animals↗
PubMed1994

5-HT1A receptors mediate the effect of the bulbospinal serotonin system on spinal dorsal horn nociceptive neurons.

The present study examined whether the effect of stimulation of the nucleus raphe magnus (NRM) is mediated by spinal cord dorsal horn serotonin1A (5-HT1A) receptors in the rat. This hypothesis predicts that nociceptive dorsal horn units inhibited by NRM stimulation or iontophoretic 5-HT application would also be inhibited by iontophoresis of the selective 5-HT1A agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and buspirone. A total of 78 dorsal horn wide-dynamic-range neurons were recorded. Overall, 62% of the cells tested (48/78) were responsive to electrical stimulation of the NRM with the predominant response being inhibitory (38/48; 79%). Fifty-eight cells were tested for their response to both NRM stimulation and 8-OH-DPAT iontophoresis: 20/58 cells were inhibited by NRM stimulation and 50% of the cells inhibited by NRM stimulation were also inhibited by 8-OH-DPAT. Fifty-two cells were tested for their response to both NRM stimulation and buspirone iontophoresis: 14/52 cells were inhibited by NRM stimulation with 9/14 similarly inhibited by buspirone. To examine whether exogenously applied serotonin produced an effect through 5-HT1A receptors, the effect of both 5-HT and 8-OH-DPAT iontophoresis was tested on 57 dorsal horn neurons. The majority of cells (25/57) were inhibited by 5-HT application; 15/25 were similarly inhibited by 8-OH-DPAT. The response of 48 dorsal horn cells to 5-HT and buspirone iontophoresis was compared. Forty-four percent (21/48) of the cells were inhibited by 5-HT; 16/21 were also inhibited by buspirone.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Echocardiographic evaluation of bupivacaine cardiotoxicity.

In nine pentobarbital anesthetized dogs, the global effects of bupivacaine on the heart were examined during and after the onset of bupivacaine cardiotoxicity. The onset of bupivacaine cardiotoxicity was followed by the use of echocardiography to determine the sequence of events. The overall sequence of changes in the heart, demonstrated by the echocardiographic images, was markedly impaired systolic function and right ventricular dilation. The right ventricular dilation was so profound that it was associated with a septal shift into the left ventricle. Right ventricular dilation was so profound that the ability to maintain the whole ventricle within the echocardiographic image was lost. Areas obtained from the left ventricle at the two time points studied (the half-time from the beginning of injection to the occurrence of asystole referred to as midway through the toxic episode and at asystole) exhibited a significant systolic dilation only midway through the toxic episode. The mean total dose of bupivacaine resulting in the dilation of the ventricles was 14.0 +/- 3.3 mg/kg. The mean arterial pressure was reduced from control by 46.9% +/- 8.8% midway through the toxic episode. The mean pulmonary arterial pressure exhibited no significant change from before the bupivacaine injection sequence. A variety of conduction changes seen midway through the toxic episode were widening of the QRS complex, inversion, bradycardia, premature ventricular contractions (PVCs), or a combination of these. PVCs, if seen at all, were only beginning to develop and no heart block was seen in any dog midway through the toxic episode.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Activation of serotonin1A receptors inhibits midbrain periaqueductal gray neurons of the rat.

The midbrain periaqueductal gray (PAG) is involved in a variety of functions including pain modulation, vocalization, autonomic control, fear and anxiety. This area contains serotonin receptors, particularly 5-HT1A that are known to play a role in the above functions. The goals of this study were to characterize the effects of 8-OH-DPAT, a selective 5-HT1A agonist, on the firing characteristics and membrane properties of PAG neurons. Both in vivo and in vitro preparations were used. The effects of 8-OH-DPAT on baseline activity of 91 neurons were tested in the in vivo preparation. In 50/91 cells, 8-OH-DPAT produced a decrease in the firing rate that ranged between 21 and 98% (mean +/- S.E.M. decrease of 49 +/- 1.9%). This inhibitory effect was dose dependent and could be blocked by spiperone. In 10/91 cells, 8-OH-DPAT produced an increase in the firing rate that ranged between 13 and 290%, with mean increase of 83 +/- 7.4%. The baseline firing rate of the remaining 31 cells was not affected by 8-OH-DPAT. In the PAG slice preparation, the effects of 8-OH-DPAT on synaptic and membrane properties of 17 PAG neurons were tested using whole-cell voltage clamp-recording procedures. In 14 cells, application of 8-OH-DPAT produced hyperpolarization that ranged between 6 and 21 mV, with mean of 8.4 +/- 2.0 mV. This hyperpolarization was associated with a decrease in membrane impedance that ranged between 8 and 45%, with mean decrease of 21.6 +/- 4.5%. The remaining three neurons did not respond to 8-OH-DPAT.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Intracellular filling in fixed brain slices using Miniruby, a fluorescent biocytin compound.

Biocytin is useful for intracellular filling in living slices because it is soluble, has high electrophoretic mobility and a high affinity for avidin. In fixed slices, however, membrane potential cannot be used to signify that a cell is impaled. Thus, it is necessary to inject a fluorescent molecule so that impalement and filling can be visually monitored. As biocytin does not fluoresce, it cannot be used by itself in fixed slices. Here, we report that a biocytin-dextran (MW 10 kDa and 40 kDa) compound, Miniruby (MR), is a useful intracellular marker for injecting neurons in fixed slices. Fixed slices (200-400 microns) of adult rat olfactory bulb, piriform cortex, midbrain periaqueductal gray and locus coeruleus were used. Slices were stained by 0.001% ethidium bromide so that cell bodies could be visualized. The slices were imaged and filled using a specially designed hinged, epi-fluorescent microscope. A cell was impaled with a pipette containing 1-5% MR; positive pulsed constant current (1-5 nA; 300-400 ms on and 600-700 ms off; approximately 10 min) was applied until the fine dendrites were brightly fluorescent. Slices were post-fixed for 6-12 h, then reacted by a conventional ABC-DAB protocol. Miniruby has several advantages: (1) it is easy to visualize the electrode in relation to the cell bodies; (2) the staining procedure is very sensitive, does not require immunohistochemistry, and the reaction product is light stable; (3) injected neurons, dendrites and initial part of axons are well visualized by bright-field microscopy. It should be possible to analyze MR filled cells at the EM level.

Animals↗
PubMed1993

Electrophysiological characterization of the projection from the nucleus raphe magnus to the lateral reticular nucleus: possible role of an excitatory amino acid in synaptic activation.

Numerous studies have shown that the lateral reticular nucleus (LRN), located in the caudal ventrolateral medulla, is an important nuclear region in the descending analgesia system. Activation of this brainstem region, either electrically or chemically, results in a reduction in nociceptive threshold. In addition, destruction of LRN abolishes the tonic descending inhibition present on dorsal horn neurons. Recent neuroanatomical tracing studies have shown that the nucleus raphe magnus (NRM), long implicated in nociception, sends direct projections to LRN; however, no information exists regarding the physiological characteristics of this pathway, nor its role in the endogenous descending analgesia system. The purpose of this study was to physiologically characterize the synaptic influence(s) of projections from the NRM to the LRN using electrophysiological recording, electrical and chemical stimulation, and iontophoretic techniques. Sixty-one percent of LRN neurons responded to single pulse stimulation of NRM; 52% of the responsive cells were excited and 48% were inhibited. The mean latency to onset of excitation was 4.9 +/- 1.2 ms. High frequency (100 Hz) electrical stimulation of NRM influenced 69/102 neurons; 52% (36/69) were excited, while 48% (33/69) were inhibited. Microinjection of glutamate into NRM significantly modified the discharge of 83% (93/112) of LRN cells tested; of these, 71% were inhibited, while 29% were excited. In 35 cells the effects of the excitatory amino acid antagonist kynurenic acid (KYN) were studied. In 75% of the cells excited by glutamate administration into the NRM (18/24), KYN partially antagonized this response. In 11 LRN cells inhibited by NRM chemical stimulation, KYN had no effect on this inhibition. Overall, 95% of the LRN cells responsive to NRM stimulation were also responsive to noxious peripheral stimulation, indicating that these cells are receiving ascending information from the spinal cord regarding somatosensory stimulation as well as receiving descending input from the NRM. It is concluded that LRN neurons are highly responsive to both noxious peripheral stimulation and NRM efferent activation, and that this region plays a significant role as an integrator for both ascending and descending information.

Amino Acids↗
PubMed1993

Physiological influence of lateral proisocortex on the midbrain periaqueductal gray: evidence for a role of an excitatory amino acid in synaptic activation.

Recent anatomical studies in this laboratory have demonstrated that the proisocortex cortex adjacent and dorsal to the rhinal sulcus is one of the major forebrain afferent inputs to the midbrain periaqueductal gray matter in the rat. The physiological influence(s) of this projection has not been examined. The present studies investigated the responses of periaqueductal gray neurons to chemical and electrical stimulation of proisocortex in chloral hydrate-anesthetized rats. In addition, the role of glutamate as a possible transmitter in excitatory proisocortex-periaqueductal gray synaptic responses was tested. Microinjection of D,L-homocysteate into proisocortex excited 44% (19/43), inhibited 37% (16/43) and had no effect on 19% of periaqueductal gray cells. The onset of D,L-homocystic acid-evoked responses ranged from 2 to 60 s; the duration of responses ranged from 1 to 18 min. Low-frequency, single-pulse electrical stimulation of proisocortex robustly altered neuronal discharge in 25% of periaqueductal gray neurons sampled; 10% (74/724) of neurons were excited and 15% (107/724) were inhibited. Insular cortex-evoked excitatory responses had a mean onset latency of 19.5 +/- 4.2 ms and a mean duration of 38.5 +/- 26.9 ms. Inhibitory responses had a mean onset latency of 26.2 +/- 15.6 ms and mean duration of 108.0 +/- 84.9 ms. Trains of high-frequency electrical stimulation of proisocortex excited 22% (13/59) and inhibited 25% (15/59) of periaqueductal gray cells tested. In separate experiments, stimulation electrodes were placed in periaqueductal gray to antidromically activate proisocortex neurons that project to periaqueductal gray.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1992

Actions of epinephrine on neurons in the rat midbrain periaqueductal gray maintained in vitro.

The effect of epinephrine (EPI) on the activity of 150 periaqueductal gray (PAG) neurons was examined using extracellular recordings in an in vitro slice preparation. Drop application of EPI inhibited 45%, excited 35%, and had no effect on 20% of PAG neurons. Both the excitatory and inhibitory effects of EPI were of long duration; excitatory responses averaged 17 min and inhibitory responses averaged 11 min in duration. EPI responses could be blocked by specific alpha-1 and alpha-2 receptor antagonists. In 35% of the neurons tested, blockade of synaptic transmission by perfusion with low calcium-high magnesium physiological saline blocked responses to EPI. The effects of EPI were site specific: 77% of the cells in the caudal ventrolateral region of the PAG were inhibited by EPI; in all other regions of PAG equal numbers of cells were excited and inhibited by EPI. It is concluded that: (a) EPI has potent effects on a majority (80%) of PAG neurons; (b) EPI responses are mediated by presynaptic as well as postsynaptic mechanisms; (c) EPI preferentially inhibits neurons in the ventrolateral subdivision of caudal PAG. As this part of PAG contains many neurons that project to the ventral medulla, it is possible that EPI modulates the PAG-medullary functions such as analgesia, autonomic regulation, defense reactions, and sexual behaviors.

Animals↗
PubMed1991

Evidence for glutamic acid as a possible neurotransmitter between the mesencephalic nucleus cuneiformis and the medullary nucleus raphe magnus in the lightly anesthetized rat.

Previous anatomic and behavioral studies have provided evidence for a strong projection from the mesencephalic nucleus cuneiformis (NCF) to the medullary nucleus raphe magnus (NRM), an area mediating control of a descending pain inhibitory system. Moreover, physiologic experiments in the deeply anesthetized rat have shown that this projection is predominantly excitatory and, at least partially, cholinergic. Recently Fields and coworkers have described 3 physiologically defined classes of neurons in the NRM: the off-, on-, and neutral cells, which exhibit an abrupt pause, increase, or no change in activity, respectively, just prior to the occurrence of the nocifensive tailflick (TF) reflex. The off-cells have been hypothesized as part of a negative feedback system influencing pain transmission at the spinal level. In this study we have examined the interaction between the NCF and neurons in the NRM that were classified as off-, on-, or neutral cells. In addition, since many NCF neurons are glutamatergic, we have examined the possible role of glutamate in the interaction between NCF and NRM. In the lightly anesthetized rat, low-intensity electrical stimulation of NCF excited 53% of NRM neurons at short latencies (mean onset, 3.9 ms), while 20% of NRM neurons were inhibited. Cells of all 3 NRM classes (off-, on-, and neutral) were predominantly excited, an effect which could be blocked by the broad-spectrum excitatory amino acid antagonist kynurenic acid in 36% of cells tested. Pharmacological stimulation of NCF with glutamic acid induced mixed effects, as 34% of NRM cells were excited while 37% were inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Connections between the central nucleus of the amygdala and the midbrain periaqueductal gray: topography and reciprocity.

Previous reports indicate that the midbrain periaqueductal gray and the central nucleus of the amygdala are interconnected but the organization of these projections has not been characterized. We have analyzed this reciprocal circuitry using anterograde and retrograde tracing methods and image analysis. Our findings reveal that innervation of periaqueductal gray from the central nucleus of the amygdala is extensive and discretely organized along the rostrocaudal axis of periaqueductal gray. In addition, the reciprocal projection from periaqueductal gray to the central nucleus of the amygdala is more extensive and more highly organized than previously suggested. Multiple or single discrete injections of wheatgerm agglutinin-horseradish peroxidase into several rostrocaudal levels of periaqueductal gray retrogradely labeled a substantial population of neurons, predominantly located in the medial division of the central nucleus of the amygdala. Tracer injections into the central nucleus revealed a high degree of spatial organization in the projection from this nucleus to periaqueductal gray. Two discrete longitudinally directed columns in dorsomedial and lateral/ventrolateral periaqueductal gray are heavily targeted by central amygdalar inputs throughout the rostral one-half to two-thirds of periaqueductal gray. Beginning at the level of dorsal raphe and continuing caudally, inputs from the central nucleus terminate more uniformly throughout the ventral half of periaqueductal gray. In addition, a substantial population of periaqueductal gray neurons were retrogradely labeled from the central nucleus of the amygdala; these were heterogeneously distributed along the rostrocaudal axis of periaqueductal gray, and included both raphe and non-raphe neurons. Thus, the present study demonstrates that periaqueductal gray receives heavy, highly organized projections from the central nucleus of the amygdala and, in turn, has reciprocal connections with the central nucleus. Previous studies have demonstrated that longitudinally organized columns of output neurons located in dorsomedial and lateral/ventrolateral periaqueductal gray project to the ventral medulla. Thus, there may be considerable overlap between the two longitudinally organized terminal input columns from the central nucleus of the amygdala and the two longitudinal columns of descending projection neurons from periaqueductal gray to the ventral medulla. The central nucleus of the amygdala has been implicated in a variety of emotional/cognitive functions ranging from fear and orienting responses, defensive and aversive reactions, associative conditioning, cardiovascular regulation, and antinociception. Many of these same functions are strongly represented in the periaqueductal gray. It is noteworthy that the present results demonstrate that lateral periaqueductal gray, a preeminent central trigger site for behavioral and autonomic components of the defense/aversion response, is heavily targeted by inputs from the central nucleus of the amygdala at all levels of periaqueductal gray.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholinesterase↗
PubMed1990

Thyrotropin-releasing hormone has profound presynaptic action on cultured spinal cord neurons.

Thyrotropin-releasing hormone (TRH) receptors are widely distributed throughout the nervous system. In particular, both the dorsal and the ventral horn (VH) neurons contain a rich distribution of TRH receptors, and TRH application to these sites has profound physiological effects. Currently the mechanism of action of TRH is not known. We examined the effect of TRH on ventral horn neurons using intracellular and patch-clamp techniques. Our results indicate that TRH application profoundly increases the firing rate of VH cells by decreasing membrane conductance. More importantly, TRH causes a significant increase in frequency and amplitude of postsynaptic potentials. Under voltage-clamp condition, TRH reduces holding current and causes a significant increase in the rate of occurrence and the amplitude of excitatory postsynaptic currents (EPSCs), an effect that lasts for more than 5 minutes. This effect of TRH is not observed in cultured neurons pretreated with tetanus toxin. TRH also fails to alter the characteristics of the EPSCs when it is applied to a region of the cell that is sparsely innervated. These results provide strong evidence that presynaptic mechanisms have a significant role in the excitatory effect of TRH on the VH neurons. Because there is evidence that trophic factors are released from presynaptic terminals, by increasing synaptic activity, TRH can have a trophic influence on the spinal cord neurons. In addition, because there are a significant number of TRH containing neurons within the spinal cord, it is likely that TRH has a major role in information processing within the spinal cord.

Animals↗
PubMed1990

A rapidly inactivating Ca2(+)-dependent K+ current in pheochromocytoma cells (PC12) of the rat.

The membrane electrical properties of undifferentiated pheochromocytoma cells of the rat (PC12) were studied using both current- and voltage-clamp techniques with the use of low-resistance blunt-tipped micropipettes (patch electrodes). In the presence of tetrodotoxin (TTX, 2-3 microM), a spike-like wave form with a prominent after-hyperpolarization (AHP) was recorded following brief (less than 10 ms) depolarizing current pulses. The inorganic divalent cations, Cd2+ (0.5 mM), Mn2+ (4 mM), and 0 mM Ca2+/4 mM Mg2+ solution prolonged the duration, attenuated the AHP, slowed the rate of repolarization, and slightly enhanced the amplitude of this wave form. A rapidly inactivating outward current was recorded in over 70% of the cells under voltage-clamp conditions. This transient current was elicited at about -30 mV, and was blocked by tetraethylammonium (5 mM), inorganic divalent cations (Cd2+, 0.5 mM; Mn2+, 4 mM; Ba2+, 3 mM), and removal of Ca2+ (0 mM Ca2+/4 mM Mg2+) from the local perfusion medium. In addition, 4-aminopyridine (5 mM), which blocks the transient outward K+ current IA in a variety of excitable cells, did not have any appreciable effect on this rapidly inactivating current. Moreover, it was possible to elicit the current at a holding potential of -40 mV. The reversal potential of this current was -90 mV, and shifted positively when extracellular K+ concentrations were elevated. It is concluded that PC12 cells have a rapidly inactivating Ca2(+)-dependent K+ current. A possible explanation for the transient nature of this current may be the presence of an effective intracellular Ca2+ buffering (uptake or extrusion) system.

Adrenal Gland Neoplasms↗
PubMed1990

Bulbospinal and intraspinal thyrotropin releasing hormone systems: modulation of spinal cord pain transmission.

Recent research indicates that pain processing by spinal nociceptive neurons is modulated by: 1) descending bulbospinal pathways originating in the rostral ventral medulla (RMV) and 2) short intraspinal peptide systems located in the dorsal horn. Immunohistochemical studies have identified both bulbospinal and intraspinal thyrotropin releasing hormone (TRH) systems, however, the role of these two TRH systems in pain modulation has not been defined. The purpose of the present study was to explore the role of the bulbospinal and intraspinal TRH systems in pain modulation. Three TRH mediated neural network were examined in electrophysiologic experiments; each model predicting specific testable outcomes. Model A represented a direct TRH projection from RVM to spinal cord. This model predicted that the effect of RVM stimulation and TRH micropressure administration on dorsal horn unit activity would be in the same direction, either both inhibitory effects or both excitatory. Of 44 dorsal horn units inhibited by RVM stimulation, 82% were excited by TRH, therefore, Model A was rejected. Model B interposed an intraspinal neuron between the bulbospinal TRH projection and the dorsal horn nociceptive unit. This model predicted that desensitization of spinal TRH receptor systems should block the effect of RVM stimulation on dorsal horn neuron. In TRH desensitization experiments, no attenuation or blockade of RVM stimulation was observed, therefore, the effect of RVM stimulation did not appear mediated by TRH and Model B was rejected.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The effect of [Met]enkephalin on the periaqueductal gray neurons of the rat: an in vitro study.

Intracellular and extracellular recording techniques and in vitro preparation were used to examine the effect of [Met]enkephalin on the rat periaqueductal neurons. In the 20 cells that were recorded intracellularly, [Met]enkephalin caused an increase in the resting membrane conductance, hyperpolarization of the cell membrane, an increase in the firing threshold and a decrease in the spontaneous firing rate. This effect of [Met]enkephalin could be blocked by naloxone. The effect of [Met]enkephalin on 99 neurons was also examined using extracellular recording. In 59% of cells, pressure application of [Met]enkephalin caused a dose-dependent inhibition that could be blocked by naloxone; 15% of the cells were excited and the remaining neurons (26%) did not respond. Nineteen per cent of responsive cells were located in the dorsolateral subdivision; 41% in the ventrolateral and 13% in the dorsal regions. In 10 cells, perfusion with physiological saline solution/Mg did not alter the inhibitory effect of [Met]enkephalin. However, perfusion with physiological saline solution/Mg abolished the excitatory response to [Met]enkephalin in four cells. It is concluded that: (1) the major effect of [Met]enkephalin on periaqueductal gray cells is inhibition that occurs through a direct postsynaptic process. This inhibition is probably due to an increase in permeability to potassium; (2) a small population of periaqueductal gray cells are excited by [Met]enkephalin, probably through a presynaptic process.

Animals↗