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R Bandler

Publications and source records attributed to R Bandler.

At least 37 records · Page 2Linked to original sources
PubMed1998

Vascular head pain selectively activates ventrolateral periaqueductal gray in the cat.

Electrical stimulation of the superior sagittal sinus is an experimental model of migraine which activates neurons within the upper cervical spinal cord. The ventrolateral periaqueductal gray has been proposed as an integrative centre for the autonomic and behavioural responses to deep pain and also receives significant inputs from the upper cervical spinal cord. The noxious-stimulation evoked expression of the immediate-early gene c-fos, was used to determine if sagittal sinus stimulation activates neurons of the ventrolateral periaqueductal gray. The superior sagittal sinus was stimulated in anesthetised cats and Fos-protein was detected in coronal brain sections using standard avidin-biotin immunohistochemistry. A pattern of Fos-positive cells restricted to the caudal ventrolateral periaqueductal gray was revealed suggesting that this region may mediate the pattern of somatic and autonomic responses characteristic of migraine.

Animals↗
PubMed1998

The ventrolateral periaqueductal gray projects to caudal brainstem depressor regions: a functional-anatomical and physiological study.

The reaction of shock, a precipitous, life-threatening fall in arterial pressure and heart rate, is evoked often by the combination of deep pain and blood loss following traumatic injury. A similar "shock-like" pattern of response can be evoked by excitation of the ventrolateral midbrain periaqueductal gray. Further, ventrolateral periaqueductal gray neurons are selectively activated by deep somatic or visceral pain and haemorrhage. The pathways mediating ventrolateral periaqueductal gray evoked hypotension and bradycardia are not known. In this study, the projections from the ventrolateral periaqueductal gray to "cardiovascular" regions in the caudal medulla of the rat were examined. Injections of the anterograde tracer, biotinylated dextran amine at physiologically-defined, ventrolateral periaqueductal gray depressor sites, revealed strong projections to the caudal midline medulla and to the depressor region of the caudal ventrolateral medulla. Injections of excitatory amino acids established that substantial falls in arterial pressure could be evoked from the ventrolateral periaqueductal gray-recipient parts of the caudal midline medulla. Injections of the retrograde tracer, cholera toxin subunit B at physiologically-defined, depressor sites in the caudal midline medulla and the caudal ventrolateral medulla confirmed the existence of substantial projections from the ventrolateral periaqueductal gray. Although previous studies have emphasized the importance of projections from the ventrolateral periaqueductal gray to the pressor region of the rostral ventrolateral medulla, this study has revealed the existence of strong ventrolateral periaqueductal gray projections to depressor regions within the caudal medulla (caudal midline medulla and caudal ventrolateral medulla) which likely contribute to ventrolateral periaqueductal gray-mediated hypotension and bradycardia.

Animals↗
PubMed1998

Medullary catecholaminergic projections to the ventrolateral periaqueductal gray region activated by halothane anaesthesia.

Under anaesthesia, blood loss and deep pain can evoke a premature, centrally-mediated sympathoinhibition leading to decompensated shock and sometimes even death. The central circuits evoking premature vasodepressor syncope are unknown, although medullary catecholaminergic pathways have been implicated. The ventrolateral periaqueductal gray region is one of only three brain regions in which catecholamine content is increased during halothane anaesthesia. The ventrolateral periaqueductal gray also contains neurons which are selectively activated by blood loss and deep pain, and recent work from our laboratory has suggested that it is a pivotal structure in central sympathoinhibitory circuits. Using retrograde tracing techniques combined with the immunohistochemical detection of: (i) the catecholamine synthetic enzyme, tyrosine hydroxylase and (ii) the protein product of the immediate-early gene c-fos as a marker of neuronal activation; the results of this study indicate that catecholaminergic projections from the A1, C1 and C2 regions of the medulla to the ventrolateral periaqueductal gray are activated by halothane anaesthesia. These data are consistent with the hypotheses that ascending catecholaminergic projections to the ventrolateral periaqueductal gray: (i) are a component of the central neural circuitry responsible for the sympathoinhibitory effects of halothane anaesthesia, and (ii) may contribute to the premature elicitation of vasodepressor syncope following blood loss and deep pain under conditions of anaesthesia.

Anesthesia, Inhalation↗
PubMed1998

Regional brain activation in humans during respiratory and blood pressure challenges.

1. The aim of the present study was to determine the brain sites mediating aspects of respiratory and cardiovascular control in adult humans using non-invasive functional magnetic resonance (fMRI) procedures, thereby avoiding the spatial and temporal sampling limitations associated with classic neural assessment techniques. 2. We examined activity changes across the entire brain following application of respiratory loads and upon induction of blood pressure and heart rate alterations. Magnetic resonance signals were visualized with a 1.5 Tesla scanner in healthy volunteers (22-52 years of age) using procedures that optimally assess changes in brain tissue microcirculation. Images were collected during a Valsalva manoeuvre, inspiratory loading, hypercapnia, cold pressor challenges to the hand and forehead and during intervening baseline states. 3. Image values from experimental conditions were compared with corresponding baseline values on a pixel-by-pixel basis to identify brain regions in which the experimental conditions produced physiological activation. 4. Ventilatory and pressor challenges elicited significant changes in regional image signal intensity in areas within the orbital cortex, amygdala, hypothalamus and hippocampus. Cerebellar, medullary and pontine areas were also recruited. However, while particular brain regions were only activated during specific stimuli, other regional signal changes occurred with multiple experimental manipulations. 5. The findings indicate that respiratory and cardiac challenges elicit discrete activity changes over multiple brain sites. Activated regions include structures not often related to respiratory or cardiovascular regulation, such as the cerebellum; a prominent role for limbic forebrain structures in mediating the response is also suggested. The fMRI visualization procedures may greatly assist in the determination of neural structures that mediate respiratory and cardiovascular control in humans.

Adult↗
PubMed1997

Spinal afferents to functionally distinct periaqueductal gray columns in the rat: an anterograde and retrograde tracing study.

The segmental and laminar organization of spinal projections to the functionally distinct ventrolateral (vlPAG) and lateral periaqueductal gray (lPAG) columns was examined by using retrograde and anterograde tracing techniques. It was found 1) that spinal input to both vlPAG and lPAG columns arose predominantly from neurons in the upper cervical (C1-4) and sacral spinal cord; 2) that there was a topographical separation of vl-PAG projecting and lPAG-projecting neurons within the upper cervical spinal cord; but 3) that below spinal segment C4, vlPAG-projecting and lPAG-projecting spinal neurons were similarly distributed, predominantly within contralateral lamina I, the nucleus of the dorsolateral fasciculus (the lateral spinal nucleus) and the lateral (reticular) part of lamina V. Consistent with the retrograde results, the greatest density of anterograde label, within both the vlPAG and lPAG, was found after tracer injections made either in the superficial or deep dorsal horn of the upper cervical spinal cord. Tracer injections made within the thoraco-lumbar spinal cord revealed that the vlPAG column received a convergent input from both the superficial and deep dorsal horn. However, thoraco-lumbar input to the lPAG was found to arise uniquely from the superficial dorsal horn; whereas the deep dorsal horn was found to innervate the "juxta-aqueductal" PAG region rather than projecting to the lPAG. These findings suggest that similar to spino-parabrachial projections, spinal projections to the lPAG (and juxta-aqueductal PAG) are topographically organised, with distinct subgroups of spinal neurons projecting to specific lPAG or juxta-aqueductal PAG subregions. In contrast, the vlPAG receives a convergent spinal input which arises from the superficial and deep dorsal horn of cervical, thoracic, lumbar, and sacral spinal segments.

Afferent Pathways↗
PubMed1997

Cardiovascular effects of microinjections of opioid agonists into the 'Depressor Region' of the ventrolateral periaqueductal gray region.

Microinjections of excitatory amino acids made into the ventrolateral midbrain periaqueductal gray of the rat have revealed that neurons in this region integrate a reaction characterised by quiescence, hyporeactivity, hypotension and bradycardia. Microinjections of both excitatory amino acids and opioids into the ventrolateral periaqueductal gray have shown also that it is a key central site mediating analgesia. The effects of injections of opioids into the ventrolateral periaqueductal gray on arterial pressure and heart rate or behaviour are unknown. In this study we first mapped in the rat the extent of the ventrolateral periaqueductal gray hypotensive region as revealed by microinjections of excitatory amino acids. We found that ventrolateral periaqueductal gray depressor region extended more rostrally than previously thought into the tegmentum ventrolateral to the periaqueductal gray. Subsequently we studied for the first time, the effects of microinjections of mu-, delta-, and kappa-opioid agonists made into the ventrolateral periaqueductal grey depressor region. In contrast to the effects of excitatory amino acid injections, microinjections of the mu-opioid agonist ([D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin) evoked hypertension and tachycardia at approximately 50% of sites. Similar to excitatory amino acid injections, microinjections of both the delta-opioid agonist ([D-Pen2,D-Pen5]enkephalin), and the kappa-opioid agonist ((5,7,8)-(+)-N-Methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-y l]-benzeneacetamide) evoked either a hypotension and bradycardia, or had no effect. These results indicate that different opiate receptor subtypes are present on a distinct population of ventrolateral periaqueductal gray neurons, or at different ventrolateral periaqueductal gray synaptic locations (pre- or post-synaptic).

Analgesics↗
PubMed1996

Projections from the ventrolateral periaqueductal gray to endocrine regulatory subdivisions of the paraventricular nucleus of the hypothalamus in the rat.

The ventrolateral periaqueductal gray (vlPAG) mediates quiescence, hyporeactivity, hypotension and bradycardia, a pattern of response evoked by injury or social defeat. These stimuli also evoke increased levels of vasopressin (VP) and adrenocorticotrophic hormone (ACTH). A key central nervous system (CNS) locus mediating endocrine changes is the paraventricular nucleus of the hypothalamus (PVH). We investigated the extent of vlPAG projections to PVH. Anterograde tracer injections into the vlPAG, revealed 'terminal' label in: (1) the medial, dorsal, anterior and lateral parvicellular divisions, and (2) lateral and medial posterior magnocellular divisions of the PVH. Deposits of the retrograde tracer Fast Blue, verified the projection to the PVH arising from the vlPAG.

Animals↗
PubMed1996

Common patterns of increased and decreased fos expression in midbrain and pons evoked by noxious deep somatic and noxious visceral manipulations in the rat.

Immunohistochemical detection of the protein product (Fos) of the c-fos immediate early gene was used to study neuronal activation in the rostral pons and midbrain of halothane-anesthetised rats following noxious deep somatic or noxious visceral stimulation. In animals exposed only to halothane anesthesia, Fos-like immunoreactive (IR) neurons were located in the midbrain periaqueductal gray matter, tectum, and parabrachial nucleus. Following noxious stimulation of hindlimb muscle, knee joint, vagal cardiopulmonary, or peritoneal nociceptors, there was, compared to halothane-only animals, a significant increase in the numbers of Fos-like (IR) cells in the caudal ventrolateral periaqueductal gray and the intermediate gray lamina of the superior colliculus. Given the general agreement that increased Fos expression is a consequence of increased neuronal activity, the finding that a range of noxious deep somatic and noxious visceral stimuli evoked increased neuronal activity in a discrete, caudal ventrolateral periaqueductal gray region is consistent with previous suggestions that this region is an integrator of deep noxious evoked reactions. The noxious deep somatic and noxious visceral manipulations also evoked, compared to halothane-only animals, reductions in the numbers of Fos-like IR cells in the stratum opticum of the superior colliculus and the unlaminated portion of the external subnucleus of the inferior colliculus. To our knowledge this is the first report of reductions in Fos-expression in the tectum evoked by noxious stimulation. In separate experiments, the effects of noxious deep somatic and noxious visceral manipulations on arterial pressure and heart rate were measured. The noxious visceral manipulations evoked substantial and sustained falls in arterial pressure (15-45 mmHg), and heart rate (75-100 bpm), whereas the depressor and bradycardiac effects of the noxious deep somatic manipulations were weaker, not as sustained, or entirely absent. As similar distributions and numbers of both increased and decreased Fos-like IR cells were observed after each of the deep noxious manipulations, it follows that the deep noxious evoked increases and decreases in Fos expression were not secondary to the evoked depressor or bradycardiac effects.

Animals↗
PubMed1996

A calbindin immunoreactive "deep pain' recipient thalamic nucleus in the rat.

The ventrolateral periaqueductal gray (vlPAG) is the only brain region known to receive convergent deep noxious inputs and to mediate the reactions characteristic of deep pain. Injections of biotinylated dextran into the vlPAG of the rat revealed a strong projection to a discrete, calbindin terminal-immunoreactive region of the caudal ventromedial nucleus (VMc) of the thalamus. This nucleus appears homologous to the calbindin-positive, pain- and temperature-specific-posterior ventromedial thalamic region of primates. We suggest that the vlPAG to VMc projection represents an important new route via which deep noxious inputs reach thalamus. As the rat is the species of choice in most experimental studies of pain, the functional-anatomical definition of this projection should further investigation of the thalamic representation of deep pain.

Animals↗
PubMed1996

Differential responses of lateral and ventrolateral rat periaqueductal grey neurones to noradrenaline in vitro.

1. The action of noradrenaline on the membrane properties of rat periaqueductal grey (PAG) neurones was examined using intracellular recordings in brain slices maintained in vitro. Morphological properties and the anatomical location of neurones were characterized by use of intracellular staining within biocytin. 2. Noradrenaline (0.3-100 microM) depolarized 66% (81/123) and hyperpolarized 30% (37/123) of neurones. The alpha 1- and alpha 2-adrenoceptor agonists phenylephrine and UK 14304 produced depolarizations and hyperpolarizations in all PAG neurones tested, respectively. Neurones depolarized by noradrenaline were more responsive to phenylephrine, whereas neurones hyperpolarized by noradrenaline were more responsive to UK 14304. 3. The UK 14304-induced hyperpolarizations reversed polarity at -108 +/- 2 mV (n = 11). The reversal potential increased when the extracellular potassium concentration was raised (slope = 57.8 mV/log[K+]o mM) in a manner similar to that predicted for potassium conductance. 4. The phenylephrine-induced depolarizations did not reverse polarity at negative potentials (n = 25), or did so at potentials (-119 +/- 2 mV, n = 13) more negative than the UK 14304-induced hyperpolarizations. Superfusion with low calcium (0.1 mM), high magnesium (10 mM) and either cobalt (2-4 mM), or cadmium (100 microM) usually reduced the response to phenylephrine and produced reversals near that predicted for potassium conductance. 5. The majority of the ventrolateral PAG neurones were depolarized by noradrenaline (85%, 62/73). In contrast, almost equal proportions of the lateral PAG neurones were hyperpolarized (54%, 20/37) and depolarized (46%, n = 17/37) by noradrenaline. PAG neurones depolarized or hyperpolarized by noradrenaline could not be differentiated on morphological grounds. 6. These results suggest that the net effect of noradrenaline on lateral and ventrolateral PAG neurones is to bias activity in favour of a ventrolateral PAG-mediated response pattern, which includes quiescence, hyporeactivity, hypotension and bradycardia.

Adrenergic alpha-Agonists↗
PubMed1996

Neural control of vocalization: respiratory and emotional influences.

Previous research has shown that a region of the midbrain, the periaqueductal gray matter (PAG), is critical for vocalization. In this review, we describe the results of previous investigations in which we sought to find out how PAG neurons integrate the activity and precise timing of respiratory, laryngeal, and oral muscle activity for natural-sounding vocalization using the technique of excitatory amino acid microinjections in cats. In these studies, all surgical procedures were carried out under deep anaesthesia. In the precollicular decerebrate cat two general types of vocalization, classified as voiced and unvoiced, could be evoked by exciting neurons in the lateral part of the intermediate part of the PAG. The patterns of evoked electromyographic activity were strikingly similar to previously reported patterns of human muscle activity. Coordinated patterns of activity were evoked with just-threshold excitation leading to the conclusion that patterned muscle activity corresponding to the major categories of voiced and voiceless sound production are represented in the PAG. In a parallel series of human and animal experiments, we also determined that the speech and vocalization respiratory patterns are integrated and coordinated with afferent signals related to lung volume. These data have led to the proposal of a new hypothesis for the neural control of vocalization: that the PAG is a crucial brain site for mammalian voice production, not only in the production of emotional or involuntary sounds, but also as a generator of specific respiratory and laryngeal motor patterns essential for human speech and song.

Affect↗
PubMed1995

Brain stem integration of vocalization: role of the nucleus retroambigualis.

1. The descending pathways that mediate the periaqueductal gray (PAG)-evoked coordination of respiratory, laryngeal, and orofacial activity for vocalization have yet to be delineated. Two hypotheses have been offered. One theory is that this activity is mediated by a diffuse descending projection to parvocellular reticular interneurons, adjacent to the relevant laryngeal and orofacial motoneuronal pools. The second hypothesis is that the motor activity for vocalization is integrated via a projection from the PAG to a caudal medullary column of neurons, the nucleus retroambigualis (NRA). These hypotheses were tested with the use of a series of medullary transections combined with PAG stimulation. Transections that eliminated, in a series of caudal-to-rostral steps, the NRA, also eliminated the PAG-evoked cricothyroid and most of the thyroarytenoid laryngeal motor activity. These results indicate that the final common pathway for much of the laryngeal activity in PAG-evoked vocalization includes un initial synapse in the caudal medulla, presumably in the NRA. 2. The electromyographic changes evoked by microinjection of D,L-homocysteic acid (DLH) in the NRA of the unanesthetized, precollicular decerebrate cat were analyzed in order to delineate the NRA contribution to the coordinated respiratory, laryngeal, and oral muscle changes in vocalization. A total of 415 DLH injection sites were located at or caudal to the level of the obex. Vocalization was evoked at 46 of these sites, which were all confined to a restricted region of the ventrolateral medulla 1-3 mm caudal to the obex. This region corresponded to the rostral half of the NRA and the immediately adjacent medullary tegmentum. 3. In all experiments evidence was obtained that variable muscle activation, rather than functional and integrated muscle patterns, was represented within the NRA. Vocalization evoked by DLH microinjection in the NRA was usually associated with excitation of the cricothyroid, thyroarytenoid, external oblique, internal oblique, internal intercostal, and diaphragm muscles that occurred in a different manner from site to site. That is, injection at sites separated by 0.3-0.5 mm evoked quite different responses. 4. NRA-evoked vocalization was compared with PAG-evoked vocalization using small injections (1.5-4.5 nl) into each region. As well, larger microinjections (15-120 nl) into NRA were made for comparison with previous results from the PAG using similar doses. Within the PAG, stereotyped and relatively "fixed" patterns of muscle activity are represented, whereas within the NRA there was no representation of specific muscle patterns, but rather a partial topographic separation of "premotor neurons" regulating different muscles. Correspondingly, stereotyped vocalizations were never evoked from the NRA. Further, most NRA-evoked vocalizations were unusual in quality and would not be identified generally as feline. 5. Evidence was obtained for a separation of pathways from the PAG regulating sound production and orofacial modulation of that sound. In contrast to the results from the PAG, excitation of NRA neurons rarely evoked activity in the oral muscles (genioglossus or anterior belly of digastric) or orofacial modulation of sound production. 6. Our finding suggests that the NRA serves as an important substrate for the generation of respiratory pressure and larynges adduction, which are two essential aspects of not only vocalization but also several behaviors involving Valsava maneuvers such as coughing, vomiting, and defecation.

Animals↗
PubMed1994

Quiescence and hyporeactivity evoked by activation of cell bodies in the ventrolateral midbrain periaqueductal gray of the rat.

Much evidence suggests that the midbrain periaqueductal gray region (PAG) plays a pivotal role in mediating an animal's responses to threatening, stressful, or painful stimuli. Active defensive reactions, hypertension, tachycardia and tachypnea are coordinated by a longitudinally oriented column of cells, found lateral to the midbrain aqueduct, in the caudal two-thirds of the PAG. In contrast, microinjections of excitatory amino acid (EAA) made in the ventrolateral region of the PAG in anesthetized or isolated animals evoke hypotension, bradycardia, and behavioral arrest. The aim of the present study was to examine further the effects of activation of neurons in the ventrolateral PAG. By injecting into this region low doses (40 pmol) of kainic acid (KA), a long-acting EAA, it was possible to observe a freely moving rat's behavior in a social situation (i.e., paired with a weight-matched, untreated partner). Such injected rats become quiescent, i.e., there was a cessation of all ongoing spontaneous activity. These rats were also hyporeactive: the investigative approaches of the partner failed to evoke orientation, startle reactions, or vocalization. Electroencephalographic measurements indicated that the effects of injections of KA in the ventrolateral PAG were not secondary to seizure activity. In addition to the quiescence and hyporeactivity reported here, and the hypotension and bradycardia reported previously, the ventrolateral PAG is a part of the brain from which analgesia has been readily evoked by electrical stimulation, or microinjections of either EAA or morphine. As a reaction to "deep" or "inescapable" pain, chronic injury, or defeat, animals often reduce their somatomotor activity, become more solitary, and are generally much less responsive to their environment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Columnar organization in the midbrain periaqueductal gray: modules for emotional expression?

Independent discoveries in several laboratories suggest that the midbrain periaqueductal gray (PAG), the cell-dense region surrounding the midbrain aqueduct, contains a previously unsuspected degree of anatomical and functional organization. This organization takes the form of longitudinal columns of afferent inputs, output neurons and intrinsic interneurons. Recent evidence suggests: that the important functions that are classically associated with the PAG--defensive reactions, analgesia and autonomic regulation--are integrated by overlapping longitudinal columns of neurons; and that different classes of threatening or nociceptive stimuli trigger distinct co-ordinated patterns of skeletal, autonomic and antinociceptive adjustments by selectively targeting specific PAG columnar circuits. These findings call for a fundamental revision in our concept of the organization of the PAG, and a recognition of the special roles played by different longitudinal PAG columns in co-ordinating distinct strategies for coping with different types of stress, threat and pain.

Animals↗