Chapter 17 Columnar organization in the midbrain periaqueductal gray and the integration of emotional expression

doi:10.1016/S0079-6123(08)61871-3

Progress in Brain Research

Volume 107, 1996, Pages 285-300

https://doi.org/10.1016/S0079-6123(08)61871-3 Get rights and content

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Recently, it has become clear that discrete longitudinal columns of neurons within the periaqueductal gray region (PAG) play special roles in coordinating, distinct emotional strategies for coping with different types of stress or threat. This chapter reviews the evidence in favor of columnar organization within the PAG and considers the mechanisms by which different PAG columns coordinate distinct patterns of behavioral and physiological reactions critical for survival. Anatomically, the PAG lies at a crossroads for a multitude of “emotional motor systems”. The PAG (i) receives substantial projections from limbic cortical and subcortical structures critical for the evaluation of the emotional significance of the environment; (ii) projects to somatic and autonomic pre-motor neural pools in the ventrolateral medulla; and (iii) massively innervates midline raphe and paramedian medullary neural pools; these latter projections providing major routes by which limbic cortical and subcortical structures influence neural activity within the medulla. The working hypothesis guiding the present research is that different, longitudinally organized PAG columns play potentially important roles in coordinating different emotional strategies for coping with different sets of environmental demands.

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Cited by (235)

Orchestration of innate and conditioned defensive actions by the periaqueductal gray
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The midbrain periaqueductal gray (PAG) has been recognized for decades as having a central role in the control of a wide variety of defensive responses. Initial discoveries relied primarily on lesions, electrical stimulation and pharmacology. Recent developments in neural activity imaging and in methods to control activity with anatomical and genetic specificity have revealed additional streams of data informing our understanding of PAG function. Here, we discuss both classic and modern studies reporting on how PAG-centered circuits influence innate as well as learned defensive actions in rodents and humans. Though early discoveries emphasized the PAG's role in rapid induction of innate defensive actions, emerging new data indicate a prominent role for the PAG in more complex processes, including representing behavioral states and influencing fear learning and memory.
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Detailed organisation of the human midbrain periaqueductal grey revealed using ultra-high field magnetic resonance imaging
2023, NeuroImage
The midbrain periaqueductal grey (PAG) is a critical region for the mediation of pain-related behavioural responses. Neuronal tract tracing techniques in experimental animal studies have demonstrated that the lateral column of the PAG (lPAG) displays a crude somatotopy, which is thought to be critical for the selection of contextually appropriate behavioural responses, without the need for higher brain input. In addition to the different behavioural responses to cutaneous and muscle pain – active withdrawal versus passive coping – there is evidence that cutaneous pain is processed in the region of the lPAG and muscle pain in the adjacent ventrolateral PAG (vlPAG). Given the fundamental nature of these behavioural responses to cutaneous and muscle pain, these PAG circuits are assumed to have been preserved, though yet to be definitively documented in humans. Using ultra-high field (7-Tesla) functional magnetic resonance imaging we determined the locations of signal intensity changes in the PAG during noxious cutaneous heat stimuli and muscle pain in healthy control participants. Images were processed and blood oxygen level dependant (BOLD) signal changes within the PAG determined. It was observed that noxious cutaneous stimulation of the lip, cheek, and ear evoked maximal increases in BOLD activation in the rostral contralateral PAG, whereas noxious cutaneous stimulation of the thumb and toe evoked increases in the caudal contralateral PAG. Analysis of individual participants demonstrated that these activations were located in the lPAG. Furthermore, we found that deep muscular pain evoked the greatest increases in signal intensity in the vlPAG. These data suggest that the crude somatotopic organization of the PAG may be phyletically preserved between experimental animals and humans, with a body-face delineation capable of producing an appropriate behavioural response based on the location and tissue origin of a noxious stimulus.
Transient decreases in blood pressure and heart rate with increased subjective level of relaxation while viewing water compared with adjacent ground
2022, Journal of Environmental Psychology
Over the course of human evolution, the successful detection of drinking water in arid environments mitigated the physiological stress of dehydration and acted as a strong source of natural selection for recognizing the optical cues for water and perhaps physiological indices of relief. The current research consisted of two studies investigating whether viewing water in outdoor settings affected autonomic tone and subjective ratings of relaxation. The first study examined blood pressure and heart rate of 32 participants who focused their attention on water in a swimming pool, a tree in a parking lot, and a small sign over a busy street. The results of this study showed that viewing water for 1 min 40 s reduced blood pressure reliably compared with viewing the tree and sign. Heart rate was also lower reliably while viewing water than the sign. The second study extended this research to a university arboretum, recording blood pressure, heart rate, and subjective ratings of relaxation of 73 participants successively at six sites along a 1.62 km path next to a creek, two small lakes, and the adjacent ground with open grassy areas and trees. At each site, participants alternated randomly in viewing the water or the ground first. Averaged for the six sites, analyses showed that the systolic/diastolic ratio for blood pressure and heart rate were reliably lower when viewing the water compared with the adjacent ground, an effect associated with the subjective rating of relaxation. Together, these findings indicate that viewing water can affect autonomic tone in a way that might account for the subjective rating of relaxation.
The interplay between 5-HT<inf>2C</inf> and 5-HT<inf>3A</inf> receptors in the dorsal periaqueductal gray mediates anxiety-like behavior in mice
2022, Behavioural Brain Research
The monoamine neurotransmitter serotonin (5-HT) modulates anxiety by its activity on 5-HT_2C receptors (5-HT_2CR) expressed in the dorsal periaqueductal gray (dPAG). Here, we investigated the presence of 5-HT_3A receptors (5-HT_3AR) in the dPAG, and the interplay between 5-HT_2CR and 5-HT_3AR in the dPAG in mediating anxiety-like behavior in mice. We found that 5-HT_3AR is expressed in the dPAG and the blockade of these receptors using intra-dPAG infusion of ondansetron (5-HT_3AR antagonist; 3.0 nmol) induced an anxiogenic-like effect. The activation of 5-HT_3ABR by the infusion of mCPBG [1-(m-Chlorophenyl)-biguanide; 5-HT₃R agonist] did not alter anxiety-like behaviors. In addition, blockade of 5-HT_3AR (1.0 nmol) prevented the anxiolytic-like effect induced by the infusion of the 5-HT_2CR agonist mCPP (1-(3-chlorophenyl) piperazine; 0.03 nmol). None of the treatment effects on anxiety-like behaviors altered the locomotor activity levels. The present results suggest that the anxiolytic-like effect exerted by serotonin activity on 5-HT_2CR in the dPAG is modulated by 5-HT_3AR expressed in same region.
Anger management: pSI has a say in it
2021, Neuron
Role of neuronal nitric oxide synthase on cardiovascular functions in physiological and pathophysiological states
2020, Nitric Oxide - Biology and Chemistry
This review describes and summarizes the role of neuronal nitric oxide synthase (nNOS) on the central nervous system, particularly on brain regions such as the ventrolateral medulla (VLM) and the periaqueductal gray matter (PAG), and on blood vessels and the heart that are involved in the regulation and control of the cardiovascular system (CVS). Furthermore, we shall also review the functional aspects of nNOS during several physiological, pathophysiological, and clinical conditions such as exercise, pain, cerebral vascular accidents or stroke and hypertension. For example, during stroke, a cascade of molecular, neurochemical, and cellular changes occur that affect the nervous system as elicited by generation of free radicals and nitric oxide (NO) from vulnerable neurons, peroxide formation, superoxides, apoptosis, and the differential activation of three isoforms of nitric oxide synthases (NOSs), and can exert profound effects on the CVS. Neuronal NOS is one of the three isoforms of NOSs, the others being endothelial (eNOS) and inducible (iNOS) enzymes. Neuronal NOS is a critical homeostatic component of the CVS and plays an important role in regulation of different systems and disease process including nociception. The functional and physiological roles of NO and nNOS are described at the beginning of this review. We also elaborate the structure, gene, domain, and regulation of the nNOS protein. Both inhibitory and excitatory role of nNOS on the sympathetic autonomic nervous system (SANS) and parasympathetic autonomic nervous system (PANS) as mediated via different neurotransmitters/signal transduction processes will be explored, particularly its effects on the CVS. Because the VLM plays a crucial function in cardiovascular homeostatic mechanisms, the neuroanatomy and cardiovascular regulation of the VLM will be discussed in conjunction with the actions of nNOS. Thereafter, we shall discuss the up-to-date developments that are related to the interaction between nNOS and cardiovascular diseases such as hypertension and stroke. Finally, we shall focus on the role of nNOS, particularly within the PAG in cardiovascular regulation and neurotransmission during different types of pain stimulus. Overall, this review focuses on our current understanding of the nNOS protein, and provides further insights on how nNOS modulates, regulates, and controls cardiovascular function during both physiological activity such as exercise, and pathophysiological conditions such as stroke and hypertension.

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Chapter 17 Columnar organization in the midbrain periaqueductal gray and the integration of emotional expression

Publisher Summary

Trends Neurosci.

Behav. Brain Res.

Neuroscience

Neuroscience

Trends Neurosci.

Brain Res.

Brain Res.

Neuroscience

Neuroscience

Brain Res.

Neuroscience

Neuroscience

Pain

Brain Res.

J. Auton. Nerv. Syst.

Brain mechanisms of aggression as revealed by electrical and chemical stimulation: suggestion of a central role for the midbrain periaqueductal grey region.

Prog. Psychobiol. Physiol. Psychol.

Integration of somatic and autonomic reactions within the midbrain periaqueductal grey: viscerotopic, somatotopic and functional organisation.

Prog. Brain Res.

Midbrain periaqueductal gray control of defensive behavior in the cat and the rat.

Actions of noradrenaline on rat periaqueductal gray neurones maintained in vitro.

Soc. Neurosci. Abstr.

The organization and modelling of animal aggression.

Organization of spinal and trigeminal input to the PAG.

The efferent projections of the periaqueductal gray in the rat: a Phaseolus vulgaris leucoagglutinin study. I. Ascending projections.

J. Comp. Neurol.

The efferent projections of the periaqueductal gray in the rat: a Phaseolus vulgaris leucoagglutinin study. II. Descending projections.

J. Comp. Neurol.

Functional organization of PAG neurons controlling regional vascular beds.

Halothane anaesthesia-induced activation of medullary adrenergic and noradrenergic projections to the midbrain periaqueductal gray.

Proc. Aust. Neurosci. Soc.

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

J. Comp Neurol.

Dorsal mesencephalic projections to pons medulla and spinal cord in the cat limbic and non-limbic components.

J. Comp. Neurol.

Distribution of brainstem projections from spinal lamina I neurons in the cat and the monkey.

J. Comp. Neurol.

Differential effects of ventral and dorsal periaqueductal gray (PAG) lesions on defensive responses of rats to cats, shock and taste aversion.

Soc. Neurosci Abstr.

Longitudinal neuronal organisation of defensive reactions in the midbrain periaqueductal gray region of the rat.

Exp. Brain Res.

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

Exp. Brain Res.

Organised aggressive behavior in cats after surgical isolation of the hypothalamus.

Arch. Ital. Biol.

Projections from the periaqueductal gray (PAG) to the periambigual area: relation to vagal output neurons.

Soc. Neurosci. Abstr.

The midbrain periaquedutal gray as a coordinator of action in response to fear and anxiety.

Neural organization of the defensive behavior system responsible for fear.

Psychonom. Bull. Rev.

Organization of the subcortical system governing defence and flight reactions in the cat.

J. Physiol. (London)

Influence of the surgical isolation of the hypothalamus on oxotremorine-induced rage reaction and sympathetic response in the cat.

Acta. Physiol. Acad. Sci. Hung.

A golgi study of the periaqueductal grey matter in the cat: Neuronal types and their distribution.

Exp. Brain Res.

Lesions of the periaqueductal gray and rostral ventromedial medulla disrupt antinociceptive but not cardiovascular aversive conditional responses.

J. Neurosci.