Elsevier

Neuroscience

Volume 7, Issue 1, January 1982, Pages 133-159
Neuroscience

The organization of afferent projections to the midbrain periaqueductal gray of the rat

https://doi.org/10.1016/0306-4522(82)90157-9Get rights and content

Abstract

The retrograde transport technique was utilized in the present study to investigate the afferent projections to the periaqueductal gray of the rat. Iontophoretic injections of horseradish peroxidase were made into the periaqueductal gray of 22 experimental animals and into regions adjacent to the periaqueductal gray in 6 control animals. Utilization of the retrograde transport method permitted a quantitative analysis of the afferent projections not only to the entire periaqueductal gray, but also to each of its four intrinsic subdivisions. The largest cortical input to this midbrain region arises from areas 24 and 32 in the medial prefrontal cortex. The basal forebrain provides a significant input to the periaqueductal gray and this arises predominantly from the ipsilateral lateral and medial preoptic areas and from the horizontal limb of the diagonal band of Broca. The hypothalamus was found to provide the largest descending input to the central gray. Numerous labeled cells occurred in the ventromedial hypothalamic nucleus, the lateral hypothalamic area, the posterior hypothalamic area, the anterior hypothalamic area, the perifornical nucleus and the area of the tuber cinereum. The largest mesencephalic input to the periaqueductal gray arises from the nucleus cuneiformis and the substantia nigra. The periaqueductal gray was found to have numerous intrinsic connections and contained a significant number of labeled cells both above and below the injection site in each case. Other structures containing significant label in the midbrain and isthmus region included the nucleus subcuneiformis, the ventral tegmental area, the locus coeruleus and the parabrachial nuclei. The medullary and pontine reticular formation provide the largest input to the periaqueductal gray from the lower brain stem. The midline raphe magnus and superior central nucleus also supply a significant fiber projection to the central gray. Both the trigeminal complex and the spinal cord provide a minor input to this region of the midbrain.

The sources of afferent projections to the periaqueductal gray are extensive and allow this midbrain region to be influenced by motor, sensory and limbic structures. In addition, evidence is provided which indicates that the four subdivisions of the central gray receive differential projections from the brain stem as well as from higher brain structures.

Reference (74)

  • KaelberW.W.

    Subthalamic nociceptive stimulation in the cat: effect of secondary lesions and rostral fiber projections

    Expl. Neurol.

    (1977)
  • LeichnetzG.R. et al.

    The efferent projections of the medial prefrontal cortex in squirrel monkey (Saimiri sciureus)

    Brain Res.

    (1976)
  • LewisV.A. et al.

    Morphine-induced and stimulation-produced analgesias at coincident periaqueductal central gray loci: evaluation of analgesic congruence, tolerance and cross-tolerance

    Expl. Neurol.

    (1977)
  • NautaW.J.H. et al.

    Efferent connections and nigral afferents of the nucleus accumbens septi in the rat

    Neuroscience

    (1978)
  • PertA. et al.

    Sites of morphine-induced analgesia in the primate brain: relation to pain pathways

    Brain Res.

    (1974)
  • RenaudL.P. et al.

    Electrophysiological studies of connections of hypothalamic ventromedial nucleus neurons in the rat: evidence for a role in neuroendocrine regulation

    Brain Res.

    (1975)
  • RhodesD.L. et al.

    Analgesia from rostral brain stem stimulation in the rat

    Brain Res.

    (1978)
  • RicardoJ.A.

    Efferent connections of the subthalamic region in the rat—II. The zona incerta

    Brain Res.

    (1981)
  • SakaiK. et al.

    Afferent connections of the nucleus raphe dorsalis in the cat as visualised by the horseradish peroxidase technique

    Brain Res.

    (1977)
  • SandersK. et al.

    Differential effects of noxious and nonnoxious input on neurons according to location in ventral periaqueductal gray or dorsal raphe nucleus

    Brain Res.

    (1980)
  • SirettN.E. et al.

    Angiotensin binding and pressor activity in the rat ventricular system and midbrain

    Brain Res.

    (1979)
  • SotnichenckoT.S.

    Convergence of the descending pathways of motor, visual and limbic cortex in the cat diand mesencephalon

    Brain Res.

    (1976)
  • SteinB.E. et al.

    Superior colliculus cells respond to noxious stimuli

    Brain Res.

    (1978)
  • SwansonL.W.

    Immunohistochemical evidence for a neurophysin-containing autonomie pathway arising in the paraventricular nucleus of the hypothalamus

    Brain Res.

    (1977)
  • TobiasT.J.

    Afferents to prefrontal cortex from thalamic mediodorsal nucleus in the rhesus monkey

    Brain Res.

    (1975)
  • WakefieldC. et al.

    Observations of HRP labeling following injection through a chronically implanted cannula—a method to avoid diffusion of HRP into injured fibers

    Brain Res.

    (1979)
  • YeungJ.P. et al.

    Mapping of brain sites for sensitivity to the direct application of morphine and focal electrical stimulation in the production of antinociception in the rat

    Pain

    (1977)
  • BeitzA.J.

    An analysis of regional subdivisions and neuronal populations in the rodent periaqueductal gray

    Neuroscience Abs.

    (1980)
  • BeitzA.J. et al.

    Brain functional activity during periaqueductal gray stimulation-produced analgesia: a 2-DG study

    Brain Res. Bull.

    (1981)
  • BermanN.

    Connections of the pretectum in the cat

    J. comp. Neurol.

    (1977)
  • BleierR. et al.

    A cytoarchitectonic atlas of the hypothalamus and hypothalamic third ventricle of the rat

  • BrodyM.J. et al.

    The role of the anteroventral third ventricle (AV3V) region in experimental hypertension

    Circ. Res.

    (1978)
  • ChangarisD.C. et al.

    Localization of angiotensin in rat brain

    J. Histochem. Cytochem.

    (1978)
  • ChiC.C.

    An experimental silver study of the ascending projections of the central gray substance and adjacent tegmentum in the rat with observations in the cat

    J. comp. Neurol.

    (1970)
  • ConradL.C.A. et al.

    Efferents from medial basal forebrain and hypothalamus in the rat.—1. An autoradiographic study of the medial preoptic area

    J. comp. Neurol.

    (1976)
  • CrosbyE.C. et al.

    The mammalian midbrain and isthmus regions—Part II. The fiber connections. C. The hypothalamotegmental pathways

    J. comp. Neurol.

    (1951)
  • DahlströmA. et al.

    Evidence for the existence of monoamine-containing neurons in the central nervous system—1. Demonstration of monoamines in the cell bodies of brain stem neurons

    Acta physiol. scand.

    (1964)
  • Cited by (446)

    • 5.16 - Descending Control Mechanisms

      2020, The Senses: A Comprehensive Reference: Volume 1-7, Second Edition
    • 5.11 - Ascending Pathways: Anatomy and Physiology

      2020, The Senses: A Comprehensive Reference: Volume 1-7, Second Edition
    • Opioid addiction and the cerebellum

      2019, Neuroscience and Biobehavioral Reviews
      Citation Excerpt :

      Subsequently, the effect of manipulating these projections via optogenetics or DREADDs in behavioral withdrawal symptoms induced by repeated opioid administration and antagonist-precipitated withdrawal could be assessed (Fig. 5). Interesting targets receiving monosynaptic input from the cerebellum and involved in opioid withdrawal would include areas like the locus coeruleus (Schwarz et al., 2015; Maldonado and Koob, 1993), the raphe nuclei (Asanuma et al., 1983; Jolas et al., 2000), and the periaqueductal grey (Beitz, 1982; Iida et al., 2017). Furthermore, neuroimaging studies on individuals with opioid-use disorders have shown the cerebellum to be reliably activated by presentation of opioid-associated cues to these subjects (Sell et al., 2000; Li et al., 2015; Wang et al., 2014).

    View all citing articles on Scopus
    View full text