Innervation of ventricular and periventricular brain compartments

Abstract

Synaptic transmission is divided into two broad categories on the basis of the distance over which neurotransmitters travel. Wiring transmission is the release of transmitter into synaptic clefts in close apposition to receptors. Volume transmission is the release of transmitters or modulators over varying distances before interacting with receptors. One case of volume transmission over potentially long distances involves release into cerebrospinal fluid (CSF). The CSF contains neuroactive substances that affect brain function and range in size from small molecule transmitters to peptides and large proteins. CSF-contacting neurons are a well-known and universal feature of non-mammalian vertebrates, but only supra- and subependymal serotonergic plexuses are a commonly studied feature in mammals. The origin of most other neuroactive substances in CSF is unknown. In order to determine which brain regions communicate with CSF, we describe the distribution of retrograde neuronal labeling in the rat brain following ventricular injection of Cholera toxin, β subunit (CTβ), a tracer frequently used in brain circuit analysis. Within 15 to 30 minutes following intraventricular injection, there is only diffuse, non-specific staining adjacent to the ventricular surface. Within 2 to 10 days, however, there is extensive labeling of neuronal perikarya in specific nuclear groups in the telencephalon, thalamus, hypothalamus and brainstem, many at a considerable distance from the ventricles. These observations support the view that ventricular CSF is a significant channel for volume transmission and identifies those brain regions most likely to be involved in this process.

Critical appraisal of pathology transmission in the α-synuclein fibril model of Lewy body disorders

“…Rey and colleagues performed control infusions into the cerebrospinal fluid to bolster their argument that the transmission of α-synuclein from the olfactory bulb is not attributable to ventricular diffusion (Rey et al, 2013). In previous studies, we infused tract-tracers into the lateral ventricles adjacent to the hippocampus and noted densely labeled neurons in medial hypothalamic nuclei that contact the periventricular zones of the third ventricle, as well as particularly dense labeling of the raphe complex (Leak and Moore, 2012). Serotonergic neurons of the raphe have long been known to elaborate an extensive cerebrospinal fluid-contacting terminal plexus (Aghajanian and Gallager, 1975; Chan-Palay, 1976; Richards, 1977).…”

Volume transmission of beta-endorphin via the cerebrospinal fluid; a review

“…Uptake of β-END from the CSF : For our hypothesis concerning long-distance VT, we also need to establish that specific ependymal and other cells, partially remote from the ventricular surface, are able to take up specific substances from the CSF. Such ependymal and neuronal elements are abundantly present throughout the ventricular system, including the lateral and fourth ventricles, and have been located in both forebrain (dentate area of the hippocampus, lateral septum, thalamus and hypothalamus) and a variety of brainstem areas, especially the raphe nuclei [ 51 , 53 , 161 , 184 - 186 ]. Retrograde flow mechanisms take care of the transport of substances like β-END, from the CSF towards the soma of neurons remote from the ventricles where they may elicit responses leading to changes in gene expression [ 51 ].…”

Morphology, Distribution and Phenotype of Polycystin Kidney Disease 2-like 1-Positive Cerebrospinal Fluid Contacting Neurons in The Brainstem of Adult Mice

“…Medullospinal cerebrospinal fluid contacting neurons (CSF-cNs) are part of the circumventricular organs found in the central nervous system (CNS). Some of these organs form a bridge between the CSF, the bloodstream, and neurons in the parenchyma and are also believed to be involved in neuronal volume transmission [1] – [3] . These cells are present in the wall of the ventricular cavities and around the cc and, depending on the position of their soma, they represent intra-, subependymal and distal CSF-cNs.…”