Differential subcellular localization of the 5‐HT₃‐A_s receptor subunit in the rat central nervous system

Abstract

Following the cloning and sequencing of the A subunit of the 5-HT3 receptor, two alternatively spliced isoforms, 5-HT3-AS and 5-HT3-AL, have been identified. In order to analyse the distribution of the receptor, a polyclonal antibody has been produced against the short form which is the most abundant in the central nervous system [Doucet et al. (2000) Neuroscience 95, 881-892]. As expected from the recognition of functional 5-HT3 receptors, immunostaining by this anti-5-HT3-R-AS antibody matched the distribution of the high-affinity 5-HT3 binding sites in the rat brain and spinal cord. 5-HT3-AS-like immunoreactivity was detected at low levels in the limbic system, particularly in the amygdala and the hippocampus, and in the frontal, piriform and entorhinal cortices. High levels of immunoreactivity were found in the brainstem, mainly in the nucleus tractus solitarius and the nucleus of the spinal tract of the trigeminal nerve, and in the dorsal horn of the spinal cord. At the ultrastructural level, immunostaining was generally found associated with axons and nerve terminals (70-80%) except in the hippocampus, where labelled dendrites were more abundant (56%). This preferential localization on nerve endings is consistent with the well-documented physiological role of 5-HT3 receptors in the control of neurotransmitter release. However, the different distribution in the hippocampus raises the question of whether differential addressing mechanisms exist for preferentially targeting 5-HT3 receptors to postsynaptic dendritic sites as compared to presynaptic nerve endings, depending on the nature of the neurons bearing these receptors.

Spinal Cord-Transected Mice Learn to Step in Response to Quipazine Treatment and Robotic Training

“…This putative sensory modulation role is consistent with the presence of 5-HT receptors in the dorsal horn of the lumbosacral spinal cord (Liu et al, 2002). Furthermore, numerous findings associate 5-HT with sensory input modulation (Machacek et al, 2001;Meuser et al, 2002;Miquel et al, 2002;Shay and Hochman, 2002;Bosco et al, 2003;Hains et al, 2003). In intact cats, monoamine release selectively increases the excitability of some reflex circuits but decreases the excitability of others, e.g., potentiating transmission from group I spindle fibers and tendon organs (Edgley et al, 1988;Bras et al, 1990) while depressing transmission from nociceptors and group II fibers (Headley et al, 1978; Figure 5.…”

5-HT3AReceptor-Bearing White Matter Interstitial GABAergic Interneurons Are Functionally Integrated into Cortical and Subcortical Networks

“…In fact, in many brain regions 5-HT 3 receptor-bearing neurons do not receive synaptic serotonergic innervation and serotonergic axons often do not form classical synapses (Descarries et al, 1990;Umbriaco et al, 1995), implying volume transmission as the predominant way by which serotonin exerts its function. There is also ample evidence for the existence of presynaptic 5-HT 3 receptors in different brain areas (Nichols and Mollard, 1996;Nayak et al, 1999;Miquel et al, 2002), and functional analyses demonstrated that presynaptic 5-HT 3 receptors can regulate GABA release (Ropert and Guy, 1991;Glaum et al, 1992;Koyama et al, 2000;Katsurabayashi et al, 2003;Turner et al, 2004).…”

Neuronal localization of 5-HT type 2A receptor immunoreactivity in the rat basolateral amygdala

“…The conjugation of synthetic peptides to protein carriers may create three-dimensional conformations of peptides that mimic those seen in fixed neural tissue, but may also lead to the disappearance of particular antigenic determinants. It is possible, therefore, that these differences in the preparation of the antigen might result in epitopes with distinct molecular configurations, which could produce antibodies that recognize distinct conformations of the 5-HT 2A receptor protein located in different neuronal domains, similar to the situation with different 5-HT 3R antibodies (Morales et al, 1998;Miquel et al 2002). It is also possible that these antibodies might recognize different post-translational modifications of the receptor proteins, as has been shown for different 5-HT 1A R antibodies (Anthony and Azmitia, 1997).…”