Serotonin-, substance P- or leucine-enkephalin-containing neurons in the midbrain periaqueductal gray and nucleus raphe dorsalis send projection fibers to the central amygdaloid nucleus in the rat

In this review, we discuss the usefulness of the distinction between fear and anxiety. The clinical use of the labels is ambiguous, often defining one in terms of the other. We first consider what a useful, objective, and scientifically valid definition would entail and then evaluate several fear/anxiety distinctions that have been made in the neurobiological literature. A strong distinction should specify the difference in conditions that lead to fear versus anxiety. Additionally, fear and anxiety should generate distinct sets of behaviors. Ideally, the two states should be supported by distinguishable neuroanatomical circuits. Such a conceptualization would be consistent with the National Institute of Mental Health's Research Domain Criteria (RDoc). The majority of neurobiological approaches to the fear versus anxiety distinction fail to differentiate the two states in terms of behavior, often using the exact same behavioral measures as indicators. Of the two that do, only Predatory Imminence Theory provides a distinction both in terms of cause and effect. Indeed, that approach provides a ready distinction of anxiety, fear, and panic in terms of both antecedent conditions and response selection rules. Additionally, it appeals to distinct neural circuits to generate these modes of action.Clear definitional distinctions between fear and anxiety have been elusive. There is also ambiguity in relating clinical classifications to preclinical laboratory models. The intention of this review is to describe and evaluate several neurobehavioral approaches to the distinction between fear and anxiety. A clear, research-based definition of fear and anxiety should help clarify the natural function of these brain states and point to how their dysfunction manifests as particular anxiety disorders. This relationship is becoming increasingly important with the National Institute of Mental Health's adoption of Research Domain Criteria (RDoc), which specifically attempts to link preclinical research with clinical phenomenology. The purpose of the RDoc systems is to ". . .to translate rapid progress in basic neurobiological and behavioral research to an improved integrative understanding of psychopathology and the development of new and/or optimally matched treatments for mental disorders" (National Institute of Mental Health 2013).To accomplish this goal, we will first consider the characteristics of a good definitional distinction between fear and anxiety. Then, after briefly reviewing the circuitry responsible for fear and anxiety, we will evaluate several neurobehavioral models with respect to those characteristics. Parsing the strengths and weaknesses of these models as well as analyzing the mechanisms and circuitry that underlie fear learning may point toward a better understanding of the fear/anxiety distinction. It should also help forge a clearer relationship between these models and specific anxiety disorders. We also clarify the relationship of the RDoc criteria to these animal models.

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“…the amygdala (Li et al 1990). The dorsal raphe nucleus (DRN) projects to the dorsal PAG and to the amygdala.…”

Section: Neural Circuitrymentioning

confidence: 99%

Neurobehavioral perspectives on the distinction between fear and anxiety

2015

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“…Anterograde tracing studies with Phaseolus vulgaris leucoagglutinin (PHA-L) or biotinylated dextran amine (BDA) have demonstrated that regions of the basal forebrain are heavily targeted by DRN projections (Vertes, 1991;Sim and Joseph, 1993;Morin and Meyer-Bernstein, 1999), and retrograde tracing has confirmed that this projection arises, in part, from nonserotonergic neurons (Descarries et al, 1986;Semba et al, 1988;Stratford and Wirtshafter, 1990;Li et al, 1990; Van Bockstaele et al, 1993;Petrov et al, 1994;Ford et al, 1995;Gasbarri et al, 1999; Hansue and Shammah-Lagnado, 2002;Halberstadt and Balaban, 2006a). A recent study combined BDA anterograde tracing with 5-HT-immunofluorescent staining to demonstrate that the vast majority of DRN fibers innervating the septum are nonserotonergic (Aznar et al, 2004).…”

Section: Nih Public Accessmentioning

confidence: 99%

Selective anterograde tracing of nonserotonergic projections from dorsal raphe nucleus to the basal forebrain and extended amygdala

Halberstadt

Balaban

2008

Journal of Chemical Neuroanatomy

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The dorsal raphe nucleus (DRN) contains both serotonergic and non-serotonergic projection neurons. Retrograde tracing studies have demonstrated that components of the basal forebrain and extended amygdala are targeted heavily by input from nonserotonergic DRN neurons. The object of this investigation was to examine the terminal distribution of nonserotonergic DRN projections in the basal forebrain and extended amygdala, using a technique that allows selective anterograde tracing of nonserotonergic DRN projections. To trace nonserotonergic DRN projections, animals were pretreated with nomifensine, desipramine and the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), 7 days prior to placing an iontophoretic injection of biotinylated dextran amine (BDA) into the DRN. In animals treated with 5,7-DHT, numerous nonserotonergic BDA-labeled fibers ascended to the basal forebrain in the medial forebrain bundle system. Some of these labeled fibers crossed through the lateral hypothalamus, bed nucleus of the stria terminalis, and substantial innominata. These fibers entered the amygdala through the ansa peduncularis and ramified within the central and basolateral amygdaloid nuclei. Other fibers entered the diagonal band of Broca and formed a dense plexus of labeled fibers in the dorsal half of the intermediate portion of the lateral septal nucleus and the septohippocampal nucleus. These findings demonstrate that the basal forebrain and extended amygdala receive a dense projection from nonserotonergic DRN neurons. Given that the basal forebrain plays a critical role in processes such as motivation, affect, and behavioral control, these findings support the hypothesis that nonserotonergic DRN projections may exert substantial modulatory control over emotional and motivational functions. Keywords amygdala; bed nucleus; 5,7-dihydroxytryptamine; septal nuclei; biotinylated dextran amine; tyrosine hydroxylase It is well known that the dorsal raphe nucleus contains more than half of all the serotonergic neurons in the brain (Leger and Wiklund, 1982) and is a source of projections that terminate extensively throughout the central nervous system (Vertes, 1991;Sim and Joseph, 1993;Vertes and Kocsis, 1994;Morin and Meyer-Bernstein, 1999 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. within dorsomedial (DRNdm), ventromedial (DRNvm), and lateral (DRNl) cell groups . It has been proposed that the activity of serotonergic DRN neurons plays an important role in the coordination of sensory processing and motor output with the sleep-wake-arousal cycle (Jacobs and Azmitia, 1992; Forn...

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“…In particular, in the periaqueductal gray matter (PAG) of both rats and cats, in situ hybridization and immunocytochemical techniques have shown its presence in many neurons, axons, and axon terminals (Hökfelt et al, 1977;Cuello and Kanazawa, 1978;Ljungdahl et al, 1978;Beitz, 1982;Skirboll et al, 1982;Moss and Basbaum, 1983;Gioia and Bianchi, 1988;Liu and Swenberg, 1988;Warden and Scott, 1988;Gioia and Bianchi, 1990;Li et al, 1990Li et al, , 1992Smith Guy et al, 1994).…”

mentioning

confidence: 96%

Immunocytochemical localization of substance P receptor in rat periaqueductal gray matter: A light and electron microscopic study

Barbaresi

1998

J. Comp. Neurol.

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The distribution of substance P receptor (SPR) protein in the rat periaqueductal gray matter (PAG) was investigated with a polyclonal antibody in the four subdivisions obtained by cytochrome-oxidase histochemistry (Co-hi). At light microscopic analysis, immunoreactivity appeared particularly dense in the dorsal subdivision of the PAG, was less intense in the other subdivisions, and formed several longitudinally organized columns. SPR-like immunoreactivity (SP(R-i)) was localized mostly to cell bodies and dendrites of small and medium-sized neurons, which constituted about 6% of the total neuronal population of the PAG. At the electron microscopic level, SP(R-i) could be observed on postsynaptic as well as on nonsynaptic regions of both cell bodies and dendrites. A small proportion of axons (4.2%) and axon terminals (5.3%) showed SP(R-i), the majority of labeled axon terminals, amounting to about 70% of synapsing elements, formed asymmetric synapses with dendrites. Rare astroglial processes displaying SP(R-i) were also observed scattered throughout the neuropil of all PAG subdivisions. Our observations suggest that 1) also in the PAG, SP may act in a diffuse, nonsynaptic manner, probably on targets that are distant from its sites of release; and 2) SP may modulate excitatory neurotransmission acting presynaptically on those labeled axons that form asymmetric synapses.

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Serotonin-, substance P- or leucine-enkephalin-containing neurons in the midbrain periaqueductal gray and nucleus raphe dorsalis send projection fibers to the central amygdaloid nucleus in the rat

Cited by 85 publications

References 13 publications

Neurobehavioral perspectives on the distinction between fear and anxiety

Neurobehavioral perspectives on the distinction between fear and anxiety

Selective anterograde tracing of nonserotonergic projections from dorsal raphe nucleus to the basal forebrain and extended amygdala

Immunocytochemical localization of substance P receptor in rat periaqueductal gray matter: A light and electron microscopic study

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