The periaqueductal gray and defensive behavior: Functional representation and neuronal organization

Recent findings suggest that the periaqueductal gray (PAG) can be subdivided on the basis of its anatomical connections and functional representation of cardiovascular and behavioral functions. This new scheme of subdivision postulates the existence of 4 major longitudinal columns located dorsomedial, dorsolateral, lateral and ventrolateral to the aqueduct. Attention has focussed on the lateral and ventrolateral columns, because they contain topographically distinct groups of neurons whose activation results in different forms of defensive or protective reactions. Reactions evoked from the lateral PAG column are associated with somatomotor and autonomic activation and are characteristic of an organism's response to superficial or cutaneous noxious stimuli, whereas reactions evoked from the ventrolateral PAG column are associated with somatomotor and autonomic inhibition and appear to correspond to an organism's response to deep or visceral noxious stimuli. Furthermore, the neurons of these two columns possess some degree of somatotopic and viscerotopic organization and send axon collaterals to multiple targets in the medulla. This model of PAG neuronal organization outlines the basic architectural features of a network involved in the coordinated expression of certain types of defensive/protective reactions.

[1]  R. Bandler,et al.  Flight and immobility evoked by excitatory amino acid microinjection within distinct parts of the subtentorial midbrain periaqueductal gray of the cat , 1990, Brain Research.

[2]  G. Halliday,et al.  Rostrocaudal differences in morphology and neurotransmitter content of cells in the subretrofacial vasomotor nucleus. , 1992, Journal of the autonomic nervous system.

[3]  R. Bandler,et al.  Characterization of pretentorial periaqueductal gray matter neurons mediating intraspecific defensive behaviors in the rat by microinjections of kainic acid , 1989, Brain Research.

[4]  A. Verberne,et al.  Midbrain central gray: regional haemodynamic control and excitatory amino acidergic mechanisms , 1991, Brain Research.

[5]  S M Hilton,et al.  The defence-arousal system and its relevance for circulatory and respiratory control. , 1982, The Journal of experimental biology.

[6]  A. Craig,et al.  Organization of Spinal and Trigeminal Input to the PAG , 1991 .

[7]  R. Bandler,et al.  Vocalization and marked pressor effect evoked from the region of the nucleus retroambigualis in the caudal ventrolateral medulla of the cat , 1992, Neuroscience Letters.

[8]  F. Graeff,et al.  Defensive behavior and hypertension induced by glutamate in the midbrain central gray of the rat. , 1985, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[9]  R. A. Durinyan,et al.  Cortical projections to the periaqueductal grey in the cat: A retrograde horseradish peroxidase study , 1984, Neuroscience Letters.

[10]  G. Scala,et al.  Wild running elicited by microinjections of bicuculline or morphine into the inferior colliculus of rats: Lack of effect of periaqueductal gray lesions , 1992, Pharmacology Biochemistry and Behavior.

[11]  D. Cechetto,et al.  Autonomic responses and efferent pathways from the insular cortex in the rat , 1991, The Journal of comparative neurology.

[12]  R. Bandler,et al.  Deep and superficial noxious stimulation increases Fos-like immunoreactivity in different regions of the midbrain periaqueductal grey of the rat , 1993, Neuroscience Letters.

[13]  P. Carrive.  Functional Organization of PAG Neurons Controlling Regional Vascular Beds , 1991 .

[14]  G. Holstege.  Some anatomical observations on the projections from the hypothalamus to brainstem and spinal cord: An HRP and autoradiographic tracing study in the cat , 1987, The Journal of comparative neurology.

[15]  A I Basbaum,et al.  Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. , 1984, Annual review of neuroscience.

[16]  A. Goodchild,et al.  A method for evoking physiological responses by stimulation of cell bodies, but not axons of passage, within localized regions of the central nervous system , 1982, Journal of Neuroscience Methods.

[17]  G. Leichnetz,et al.  Cortical projections to the periaqueductal gray in the monkey: A retrograde and orthograde horseradish peroxidase study , 1981, Neuroscience Letters.

[18]  C. Saper,et al.  Evidence for a cholinergic projection from the pedunculopontine tegmental nucleus to the rostral ventrolateral medulla in the rat , 1990, Brain Research.

[19]  G. Holstege.  Descending Pathways From The Periaqueductal Gray And Adjacent Areas , 1991 .

[20]  M Ennis,et al.  Connections between the central nucleus of the amygdala and the midbrain periaqueductal gray: Topography and reciprocity , 1991, The Journal of comparative neurology.

[21]  C. Saper,et al.  Organization of medullary adrenergic and noradrenergic projections to the periaqueductal gray matter in the rat , 1992, The Journal of comparative neurology.

[22]  R. Bandler,et al.  Somatic and autonomic integration in the midbrain of the unanesthetized decerebrate cat: a distinctive pattern evoked by excitation of neurones in the subtentorial portion of the midbrain periaqueductal grey , 1989, Brain Research.

[23]  D. Reis,et al.  Tonic vasomotor control by the rostral ventrolateral medulla: effect of electrical or chemical stimulation of the area containing C1 adrenaline neurons on arterial pressure, heart rate, and plasma catecholamines and vasopressin , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[24]  A. Goodchild,et al.  Vasopressor neurons in the rostral ventrolateral medulla of the rabbit. , 1985, Journal of the autonomic nervous system.

[25]  Joseph E LeDoux,et al.  Different projections of the central amygdaloid nucleus mediate autonomic and behavioral correlates of conditioned fear , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[26]  J. Courville.  The nucleus of the facial nerve; the relation between cellular groups and peripheral branches of the nerve. , 1966, Brain research.

[27]  T. Lovick.  Central Nervous System Integration of Pain Control and Autonomic Function , 1991 .

[28]  A. Goodchild,et al.  Vasomotor control by subretrofacial neurones in the rostral ventrolateral medulla. , 1987, Canadian journal of physiology and pharmacology.

[29]  A. Steffens,et al.  University of Groningen The Hypothalamus, Intrinsic Connections and Outflow Pathways to the Endocrine System in Relation to the Control of Feeding and Metabolism Luiten, , 2002 .

[30]  J. Lipski,et al.  Limitations of the technique of pressure microinjection of excitatory amino acids for evoking responses from localized regions of the CNS , 1988, Journal of Neuroscience Methods.

[31]  R. Bandler,et al.  Integration of somatic and autonomic reactions within the midbrain periaqueductal grey: viscerotopic, somatotopic and functional organization. , 1991, Progress in brain research.

[32]  R. Bandler,et al.  Integrated defence reaction elicited by excitatory amino acid microinjection in the midbrain periaqueductal grey region of the unrestrained cat , 1988, Brain Research.

[33]  M. T. Shipley,et al.  Reciprocal connections between the medial preoptic area and the midbrain periaqueductal gray in rat: A WGA‐HRP and PHA‐L study , 1992, The Journal of comparative neurology.

[34]  R. Nieuwenhuys,et al.  Hypothalamic Projections to the PAG in the Rat: Topographical, Immuno-Electronmicroscopical and Functional Aspects , 1991 .

[35]  Peter Redgrave,et al.  Does the PAG Learn about Emergencies from the Superior Colliculus , 1991 .

[36]  W. H. Rohrer,et al.  Organization of the projection from the superficial to the deep layers of the hamster's superior colliculus as demonstrated by the anterograde transport of Phaseolus vulgaris leucoagglutinin , 1989, The Journal of comparative neurology.

[37]  K. Sripanidkulchai,et al.  The topography of the mesencephalic and pontine projections from the cingulate cortex of the rat , 1984, Brain Research.

[38]  S. W. Ranson,et al.  ELECTRICAL STIMULATION OF POINTS IN THE FOREBRAIN AND MIDBRAIN: THE RESULTANT ALTERATIONS IN BLOOD PRESSURE , 1935 .

[39]  Richard Bandler,et al.  Brain mechanisms of aggression as revealed by electrical and chemical stimulation: suggestion of a central role for the midbrain periaqueductal grey region , 1988 .

[40]  Dennis McGinty,et al.  Keeping cool: a hypothesis about the mechanisms and functions of slow-wave sleep , 1990, Trends in Neurosciences.

[41]  W. Redfern,et al.  A search for brain stem cell groups integrating the defence reaction in the rat. , 1986, The Journal of physiology.

[42]  C. Saper,et al.  Efferent projections of the infralimbic cortex of the rat , 1991, The Journal of comparative neurology.

[43]  P. Guyenet.  Role of the ventral medulla oblongata in blood pressure regulation , 1990 .

[44]  R. Bandler.  Induction of ‘page’ following microinjections of glutamate into midbrain but not hypothalamus of cats , 1982, Neuroscience Letters.

[45]  G. Holstege.  Descending motor pathways and the spinal motor system: limbic and non-limbic components. , 1991, Progress in brain research.

[46]  R. Dampney,et al.  Vasomotor neurons in the rostral ventrolateral medulla are organized topographically with respect to type of vascular bed but not body region , 1990, Neuroscience Letters.

[47]  T. Lovick.  Interactions Between Descending Pathways from the Dorsal and Ventrolateral Periaqueductal Gray Matter in the Rat , 1991 .

[48]  S. T. Meller,et al.  Efferent projections of the periaqueductal gray in the rabbit , 1991, Neuroscience.

[49]  M. T. Shipley,et al.  Topographical Specificity of Forebrain Inputs to the Midbrain Periaqueductal Gray: Evidence for Discrete Longitudinally Organized Input Columns , 1991 .

[50]  D. Reis,et al.  The Cl Area of the Brainstem in Tonic and Reflex Control of Blood Pressure State of the Art Lecture , 1988, Hypertension.

[51]  R. Bandler,et al.  Anatomical evidence that hypertension associated with the defence reaction in the cat is mediated by a direct projection from a restricted portion of the midbrain periaqueductal grey to the subretrofacial nucleus of the medulla , 1988, Brain Research.

[52]  M. Jouvet,et al.  The Nuclei of origin of monoaminergic, peptidergic, and cholinergic afferents to the cat nucleus reticularis magnocellularis: A double‐labeling study with cholera toxin as a retrograde tracer , 1988, The Journal of comparative neurology.

[53]  R. McAllen,et al.  Differential control of sympathetic fibres supplying hindlimb skin and muscle by subretrofacial neurones in the cat. , 1988, The Journal of physiology.

[54]  A. Basbaum,et al.  Collateralization of periaqueductal gray neurons to forebrain or diencephalon and to the medullary nucleus raphe magnus in the rat , 1991, Neuroscience.

[55]  P. Izzo.  A note on the use of biocytin in anterograde tracing studies in the central nervous system: Application at both light and electron microscopic level , 1991, Journal of Neuroscience Methods.

[56]  R. Dampney.  The subretrofacial vasomotor nucleus: Anatomical, chemical and pharmacological properties and role in cardiovascular regulation , 1994, Progress in Neurobiology.

[57]  R. Bandler,et al.  Midbrain Periaqueductal Gray Control of Defensive Behavior in the Cat and the Rat , 1991 .

[58]  V. C. Abrahams,et al.  The role of active muscle vasodilatation in the alerting stage of the defence reaction , 1964, The Journal of physiology.

[59]  E. Kirkman,et al.  The involvement of the midbrain periaqueductal grey in the cardiovascular response to injury in the conscious and anaesthetized rat , 1990, Experimental physiology.

[60]  M. Wiberg,et al.  The spinomesencephalic tract in the cat: Its cells of origin and termination pattern as demonstrated by the intraaxonal transport method , 1984, Brain Research.

[61]  G. Aston-Jones,et al.  Subregions of the periaqueductal gray topographically innervate the rostral ventral medulla in the rat , 1991, The Journal of comparative neurology.

[62]  R. Yezierski.  Spinomesencephalic tract: Projections from the lumbosacral spinal cord of the rat, cat, and monkey , 1988, The Journal of comparative neurology.

[63]  T. Lovick,et al.  Differential control of cardiac and vasomotor activity by neurones in nucleus paragigantocellularis lateralis in the cat. , 1987, The Journal of physiology.

[64]  D. V. Reynolds,et al.  Surgery in the Rat during Electrical Analgesia Induced by Focal Brain Stimulation , 1969, Science.

[65]  W. Willis,et al.  Anatomy and physiology of descending control of nociceptive responses of dorsal horn neurons: comprehensive review. , 1988, Progress in brain research.

[66]  V. C. Abrahams,et al.  Active muscle vasodilatation produced by stimulation of the brain stem: its significance in the defence reaction , 1960, The Journal of physiology.

[67]  R. Bandler,et al.  Anatomical evidence for segregated input from the upper cervical spinal cord to functionally distinct regions of the periaqueductal gray region of the cat , 1992, Neuroscience Letters.

[68]  R. Bandler,et al.  Viscerotopic control of regional vascular beds by discrete groups of neurons within the midbrain periaqueductal gray , 1989, Brain Research.

[69]  R. Bandler,et al.  Viscerotopic organization of neurons subserving hypotensive reactions within the midbrain periaqueductal grey: a correlative functional and anatomical study , 1991, Brain Research.

[70]  R. Bandler,et al.  Excitation of neurones in a restricted portion of the midbrain periaqueductal grey elicits both behavioural and cardiovascular components of the defence reaction in the unanaesthetised decerebrate cat , 1987, Neuroscience Letters.

[71]  G. Holstege.  Anatomical study of the final common pathway for vocalization in the cat , 1989, The Journal of comparative neurology.