The differential projections from the dorsal raphe and median raphe nuclei of the midbrain were autoradiographically traced in the rat brain after 3H-proline micro-injections. Six ascending fiber tracts were identified, the dorsal raphe nucleus being the sole source of four tracts and sharing one with the median raphe nucleus. The tracts can be classified as those lying within the medial forebrain bundle (dorsal raphe forebrain tract and the median raphe forebrain tract) and those lying entirely outside (dorsal raphe arcuate tract, dorsal raphe periventricular tract, dorsal raphe cortical tract, and raphe medial tract). The dorsal raphe forebrain tract lies in the ventrolateral aspect of the medial forebrain bundle (MFB) and projects mainly to lateral forebrain areas (e.g., basal ganglion, amygdala, and the pyriform cortex). The median raphe forebrain tract lies in the ventromedial aspect of the MFB and projects to medial forebrain areas (e.g., cingulate cortex, medial septum, and hippocampus). The dorsal raphe cortical tract lies ventrolaterally to the medial longitudinal fasciculus and projects to the caudate-putamen and the parieto-temporal cortex. The dorsal raphe periventricular tract lies immediately below the midbrain aqueduct and projects rostrally to the periventricular region of the thalamus and hypothalamus. The dorsal raphe arcuate tract curves laterally from the dorsal raphe nucleus to reach the ventrolateral edge of the midbrain and projects to ventrolateral geniculate body nuclei and the hypothalamic suprachiasmatic nuclei. Finally, the raphe medial tract receives fibers from both the median and dorsal raphe nuclei and runs ventrally between the fasciculus retroflexus and projects to the interpeduncular nucleus and the midline mammillary body.



Further studies were done to test whether the fiber tracts travelling in the MFB contained 5-HT. Unilateral (left) injections of 5,7-dihydroxytryptamine (5 μgm/400 nl) 18 days before midbrain raphe microinjections of 3H-proline produced a reduction in the grain concentrations in all the ascending fibers within the MFB. Furthermore, pharmacological and behavioural evidence was obtained to show that the 5-HT system had been unilaterally damaged; these animals displayed preferential ipsilateral turning in a rotameter which was strongly reversed to contralateral turning after 5-hydroxytryptophan administration.



The results show that DR and MR nuclei have numerous ascending projections whose axons contain the transmitter 5-HT. The results agree with the neuroanatomical distribution of the 5-HT system previously determined biochemically, histochemically, and neurophysiologically. The midbrain serotonin system seems to be organized by a series of fiber pathways. The fast transport rate in these fibers was found to be about 108 mm/day.

An autoradiographic analysis of the differential ascending projections of the dorsal and median raphe nuclei in the rat

Feelings are mental experiences of body states. They signify physiological need (for example, hunger), tissue injury (for example, pain), optimal function (for example, well-being), threats to the organism (for example, fear or anger) or specific social interactions (for example, compassion, gratitude or love). Feelings constitute a crucial component of the mechanisms of life regulation, from simple to complex. Their neural substrates can be found at all levels of the nervous system, from individual neurons to subcortical nuclei and cortical regions.

The nature of feelings: evolutionary and neurobiological origins

Functional characteristics of the midbrain periaqueductal gray

The afferent connections of the habenular complex in the rat were examined by injecting horseradish peroxidase (HRP) into discrete portions of the habenular nuclei by microelectrophoresis.

Afferent connections of the habenular nuclei in the rat. A horseradish peroxidase study, with a note on the fiber‐of‐passage problem

A model of fear and pain is presented in which the two are assumed to activate totally different classes of behavior. Fear, produced by stimuli that are associated with painful events, results in defensive behavior and the inhibition of pain and pain-related behaviors. On the other hand, pain, produced by injurious stimulation, motivates recuperative behaviors that promote healing. In this model injurious stimulation, on the one hand, and the expectation of injurious stimulation, on the other hand, activate entirely different motivational systems which serve entirely different functions. The fear motivation system activates defensive behavior, such as freezing and flight from a frightening situation, and its function is to defend the animal against natural dangers, such as predation. A further effect of fear motivation is to organize the perception of environmental events so as to facilitate the perception of danger and safety. The pain motivation system activates recuperative behaviors, including resting and body-care responses, and its function is to promote the animal's recovery from injury. Pain motivation also selectively facilitates the perception of nociceptive stimulation. Since the two kinds of motivation serve different and competitive functions, it might be expected that they would interact through some kind of mutual inhibition. Recent research is described which indicates that this is the case. The most important connection is the inhibition of pain by fear; fear has the top priority. This inhibition appears to be mediated by an endogenous analgesic mechanism involving the endorphins. The model assumes that fear triggers the endorphin mechanism, thereby inhibiting pain motivation and recuperative behaviors that might compete with effective defensive behavior.

A perceptual-defensive-recuperative model of fear and pain

Evidence that substance P is a neurotransmitter of baro- and chemoreceptor afferents in nucleus tractus solitarius

To obtain more evidence in support of the theory of tri-nuclear division of the periaqueductal gray matter (PAG) in the cat, the projection systems of each of the nuclei were investigated Direct current lesions were stereotaxically placed in the three nuclei of the PAG and the resulting fibers of degeneration were stained by reduced silver impregnation techniques Degenerating axons from the lesion in the nucleus medialis were traced ventrally to the tegmentum in a radiating pattern and rostrally to the fields of Forel and the ventral tegmental area Descending fibers were traced to their termination in the dorsal tegemental nucleus Lesions in the nucleus dorsalis resulted in no radiating or descending fibers of degeneration, but a bundle of degenerating fibers running within the PAG could be followed to the level of the mesencephalic-diencephalic junction Here the axons terminated in the pretectal area and the lateral habenular nucleus The pattern of degeneration was completely ipsilateral for the two nuclear lesions described above and predominately ipsilateral for the third nucleus, the lateralis From it, all the ascending fibers were ipsilateral, but the heavy radiating fibers to the tectum and tegmentum did extend somewhat to the contralateral side The large bundle of axons of degeneration ran rostrally within the PAG to diencephalic levels and divided into numerous fasciculi and terminated in the periventricular gray, the posterior hypothalamus and numerous thalamic nuclei The evidence that each nucleus projects differently supports the theory of tri-nuclear division of the PAG

Projections of the nuclei of the periaqueductal gray matter in the cat.

Blockade of gamma-aminobutyric acid (GABA) receptor function by direct microinjection of the GABA receptor antagonist bicuculline into the nucleus ambiguus of the brainstem produced a marked, dose-related depression of heart rate and blood pressure which was mediated by the vagus nerve. This effect was not obtained in other regions of the brainstem and was reversed by the GABA receptor agonist muscimol. These data indicate that the nucleus ambiguus may be the site of a GABA receptor-mediated inhibition of vagal outflow.

GABA receptor control of parasympathetic outflow to heart: characterization and brainstem localization

Cardiovascular responses to electrical stimulation of the medullary raphe area of the cat

The neuronal population of the PAG consists of relatively small cells, ranging from approximately 8 μ to 30 μ in diameter. These neurons are of three different types and are classified as I, II, and III for the sake of convenience. Each class aggregates in certain areas of the central gray to form subdivisions distinguishable by differing neuronal distributions as well as by cellular characteristics. Class I neurons are small, spindle shaped cells that stain darkly with cresyl violet. They aggregate loosely around the cerebral aqueduct, thus forming the comparatively acellular inner ring of the PAG, the nucleus medialis. The class II cells are also small and darkly staining, but they are fusiform to spherical in shape. These cells cluster more closely and are surrounded by many glial cells. They congregate in the area dorsal to the cerebral aqueduct to form the nucleus dorsalis. The largest cells of the PAG, the class III neurons are spherical or tringular in shape and stain lightly due to their sparse Nissl substance. Frequently glial cells abut the perikaryon of these neurons. They aggregate very closely to form the dense cellular outer portion of the PAG. This mantle of cells is called the nucleus lateralis.

Betty L. Hamilton

Papers

Evidence that substance P is a neurotransmitter of baro- and chemoreceptor afferents in nucleus tractus solitarius

Projections of the nuclei of the periaqueductal gray matter in the cat.

GABA receptor control of parasympathetic outflow to heart: characterization and brainstem localization

Cardiovascular responses to electrical stimulation of the medullary raphe area of the cat

Cytoarchitectural subdivisions of the periaqueductal gray matter in the cat