From behavioral context to receptors: serotonergic modulatory pathways in the IC

Serotonin (5-hydroxytryptamine; 5-HT) is a monoamine neurotransmitter whose effects are mediated by at least 13 distinct G protein-coupled receptors (GPCRs) of the type A family which includes the monoamine receptors and a combination of ligand-gated ion channels (5-HT3) of the Cys loop family which constitutes heteropentamers. 5-HT receptors are currently divided into seven classes (5-HT1 to 5-HT7), based on structural, transductional and operational features. While this degree of physical diversity clearly underscores the physiological importance of serotonin, evidence for an even greater degree of operational diversity is supported by the existence of a great number of splice and editing variants for several 5-HT receptors, their possible modulation by accessory proteins and chaperones, as well as their potential to form homo or heteromers both at the GPCR and at the ligand-gated channel level.

This paper describes the distribution of structures stained with mono- and polyclonal antibodies to the calcium-binding proteins calbindin D-28k and parvalbumin in the nervous system of adult rats. As a general characterization it can be stated that calbindin antibodies mainly label cells with thin, unmyelinated axons projecting in a diffuse manner. On the other hand, parvalbumin mostly occurs in cells with thick, myelinated axons and restricted, focused projection fields. The distinctive staining with antibodies against these two proteins can be observed throughout the nervous system. Calbindin D-28k is primarily associated with long-axon neurons (Golgi type I cells) exemplified by thalamic projection neurons, strionigral neurons, nucleus basalis Meynert neurons, cerebellar Purkinje cells, large spinal-, retinal-, cochlear- and vestibular ganglion cells. Calbindin D-28k occurs in all major pathways of the limbic system with the exception of the fornix. Calbindin D-28k is, however, also found in some short-axon cells (Golgi type II), represented by spinal cord interneurons in layer II and interneurons of the cerebral cortex. It is also detectable in some ependymal cells and abundantly occurs in vegetative centres of the hypothalamus. The "paracrine core" of the nervous system and its adjunct (1985, Nieuwenhuys, Chemoarchitecture of the Brain. Springer, Berlin) is very rich in calbindin D-28k. The distribution of calbindin D-28k-positive neurons is very similar to that of the dihydroperydine subtype of calcium channels. Most of the cells containing calbindin D-28k are vulnerable to neurodegenerative processes. Parvalbumin-immunoreactive neurons have a different, and mostly complementary distribution compared with those which react with calbindin D-28k antisera, but in a few cases (Purkinje cells of the cerebellum, spinal ganglion neurons), both calcium-binding proteins co-exist in the same neuron. Many parvalbumin-immunoreactive cells in the central nervous system are interneurons (Golgi type II) and, to a lesser extent, long-axon cells (Golgi type I), whereas conditions are vice versa in the peripheral nervous system. Intrinsic parvalbuminic neurons are prominent in the cerebral cortex, hippocampus, cerebellar cortex and spinal cord. Long-axon parvalbumin-immunoreactive neurons are, for example, the Purkinje cells, neurons of the thalamic reticular nucleus, globus pallidus, substantia nigra (pars reticulata) and a subpopulation among large spinal-, retinal-, cochlear- and vestibular ganglion cells. Parvalbumin is rich in cranial nerve nuclei related to eye movements. In addition to nervous elements, parvalbumin immunoreactivity occurs in a few ependymal cells and in some pillar cells of the organ of Corti.(ABSTRACT TRUNCATED AT 400 WORDS)

The expression patterns of 13 GABAA receptor subunit encoding genes (alpha 1-alpha 6, beta 1-beta 3, gamma 1-gamma 3, delta) were determined in adult rat brain by in situ hybridization. Each mRNA displayed a unique distribution, ranging from ubiquitous (alpha 1 mRNA) to narrowly confined (alpha 6 mRNA was present only in cerebellar granule cells). Some neuronal populations coexpressed large numbers of subunit mRNAs, whereas in others only a few GABAA receptor-specific mRNAs were found. Neocortex, hippocampus, and caudate-putamen displayed complex expression patterns, and these areas probably contain a large diversity of GABAA receptors. In many areas, a consistent coexpression was observed for alpha 1 and beta 2 mRNAs, which often colocalized with gamma 2 mRNA. The alpha 1 beta 2 combination was abundant in olfactory bulb, globus pallidus, inferior colliculus, substantia nigra pars reticulata, globus pallidus, zona incerta, subthalamic nucleus, medial septum, and cerebellum. Colocalization was also apparent for the alpha 2 and beta 3 mRNAs, and these predominated in areas such as amygdala and hypothalamus. The alpha 3 mRNA occurred in layers V and VI of neocortex and in the reticular thalamic nucleus. In much of the forebrain, with the exception of hippocampal pyramidal cells, the alpha 4 and delta transcripts appeared to codistribute. In thalamic nuclei, the only abundant GABAA receptor mRNAs were those of alpha 1, alpha 4, beta 2, and delta. In the medial geniculate thalamic nucleus, alpha 1, alpha 4, beta 2, delta, and gamma 3 mRNAs were the principal GABAA receptor transcripts. The alpha 5 and beta 1 mRNAs generally colocalized and may encode predominantly hippocampal forms of the GABAA receptor. These anatomical observations support the hypothesis that alpha 1 beta 2 gamma 2 receptors are responsible for benzodiazepine I (BZ I) binding, whereas receptors containing alpha 2, alpha 3, and alpha 5 contribute to subtypes of the BZ II site. Based on significant mismatches between alpha 4/delta and gamma mRNAs, we suggest that in vivo, the alpha 4 subunit contributes to GABAA receptors that lack BZ modulation.