Monday, May 19, 2008

"Sky-blue place" III: Input

In reference to "Sky-blue place" II: Projections:

In the post referenced above I provided a very very sketchy list of all the places LC fibers go to, what they affect, i.e., which parts hear the "alarm."

I now have pages and pages of info on that, but finding out which bits feed into LC is a bit harder. I guess the pathways are a bit less well worked out.

The Appenzeller source lists a couple of places, nucleus paragigantocellularis lateralis (of the rostral ventrolateral medulla), and nucleus prepositus hypoglossi of the rostral dorsomedial medulla.

Nucleus paragigantocellularis lateralis (what a name!) corresponds neuroanatomically to the neurochemical localization of C1 and A1 epinephrine and norepinephrine-containing cell bodies near the ventral surface of the brainstem. Nucleus prepositus hypoglossi corresponds to the localization of C3 adrenergic neurones near the dorsal surface of the medulla bordering on the 4th ventricle. (Riveting, I know..)

Other than that, apparently LC receives neurons from itself, with collaterals. Appenzeller says, p. 162:
"Both external and internal perturbations can activate the locus ceruleus, the latter after sensory processing in the medullary nuclei. Thus, if a stimulus were perceived as novel, severe or threatening, locus ceruleus activation could foster transmission of the signal to higher brain centers, facilitating active attention and memory consolidation and further orienting the organism to the stimulus."

The brain can perturb its own LC. Maybe it's the LC that becomes activated during times of cognitive dissonance.

New Territory

I looked into those two medullary or brainstem nuclei, which took me into the reticular formation, from which I'm yet to emerge. It is not an easy place to grasp. Gray's Anatomy (39th) says, (p. 347):
"The brain stem contains extensive fields of intermingled neurones and nerve fibres, which are collectively termed the reticular formation. The reticular regions are often regarded as phylogenetically ancient, representing a primitive nerve network upon which more anatomically organized, functionally selective, connections have developed during evolution. However, the most primitive nervous systems show both diffuse and highly organized regions, which cooperate in response to different demands.

"The general characteristics of reticular regions may be summarized as follows. They tend to be ill-defined collections of neurones and fibres with diffuse connections. Their conduction paths are difficult to define, complex and often polysynaptic, and they have ascending and descending components that are partly crossed and uncrossed. Their components subserve somatic and visceral functions. They include distinct chemoarchitectonic nuclear groups, including clusters of serotoninergic neurones (group B cells), which synthesize the indolamine 5-hydroxytryptamine (serotonin); cholinergic neurones (group Ch cells), which contain acetyltransferase, the enzyme which catalyses the synthesis of acetylcholine; and three catecholaminergic groups composed of noradrenergic (group A), adrenergic (group C), and dopaminergic (group A) neurones, which synthesize noradrenaline (norepinephrine), adrenaline (epinephrine) and dopamine respectively as neurotransmitters."

This seems daunting, but in persevering, I am learning quite a bit about the reticular formation system(s). They are generally grouped into three systems, raphe or median, medial (just to be confusing) located between the raphe and lateral, the third.

Are the neurons coming or going to LC?

The raphe system seems to connect to LC, but are the neurons afferent or efferent? From Gray's:
"the dorsal raphe nucleus, in addition to sending a large number of fibres to the locus coeruleus, projects to the dorsal tegmental nucleus and most of the rhombencephalic reticular formation, together with the central superior, pontine raphe and raphe magnus nuclei."

However, another source, an online book, Basic Neurochemistry, in its page on serotonin, says:
"The raphe nuclei also receive input from other cell body groups in the brainstem, such as the substantia nigra and ventral tegmental area (dopamine), superior vestibular nucleus (acetylcholine), locus ceruleus (norepinephrine) and nucleus prepositus hypoglossi and nucleus of the solitary tract (epinephrine)."

Regarding pain modulation

In Gray's this tantalizing bit appears: "Raphe spinal serotoninergic axons originate mainly from neurones in the raphe magnus, pallidus and obscurus nuclei. They project as ventral, dorsal and intermediate spinal tracts in the ventral and lateral funiculi, and terminate respectively in the ventral horns and laminae I, II and V of the dorsal horns of all segments, and in the thoracolumbar intermediolateral sympathetic and sacral parasympathetic preganglionic cell columns. The dorsal raphe spinal projections function as a pain-control pathway that descends from the mesencephalic pain-control centre, which is located in the periaqueductal grey matter, dorsal raphe and cuneiform nuclei. The intermediate raphe spinal projection is inhibitory, and, in part, modulates central sympathetic control of cardiovascular function. The ventral raphe spinal system excites ventral horn cells and could function to enhance motor responses to nociceptive stimuli and to promote the flight and fight response."

To be continued.

1. Atlas of Functional Neurology (2006) Hendelman W (p. 114-19)
2. Gray's Anatomy (39th ed.) p. 347-350
3. Handbook of Clinical Neurology: The Autonomic Nervous System Part I, Elsevier 2000, Appenzeller O., Vinken PJ, Bruyn GW, p. 155
4. Basic Neurochemistry (1999) Siegal G

Additional reading:
1. Brainstem (scholarpedia)

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