Comparative anatomical distribution of 5-HT1A receptor mRNA and 5-HT1A binding in rat brain — a combined in situ hybridisation/in vitro receptor autoradiographic study

Abstract

The present study examined the comparative distribution of 5-HT1A receptor mRNA and 5-HT1A receptors in rat brain using a combination of in situ hybridisation histochemistry and in vitro receptor autoradiography. 5-HT1A mRNA was visualized using a 910 bp cRNA probe synthesised from a BalI-PvuII fragment of the rat 5-HT1A reetor gene, while 5-HT1A receptors were labelled with the 5-HT1A-selective ligand 8-OH-DPAT. In general terms, there was a complementary distribution of cells expressing 5-HT1A receptor mRNA and 5-HT1A receptor sites. High levels of both 5-HT1A mRNA and 5-HT1A receptors were evident in the hippocampal formation (CA1, CA3, dentate gyrus), entorhinal cortex, and raphe nuclei and lower levels in neocortex and thalamus. Although 5-HT1A mRNA was not expressed in any regions which did not also exhibit 5-HT1A receptors, within both the diagonal band and the medial septal nucleus mRNA levels were proportionately higher than 5-HT1A receptor levels, possibly reflecting receptor transport or a heterogeneity in 5-HT1A receptor turnover mechanisms. 5-HT1A receptor mRNA and 5-HT1A binding sites were undetectable in caudate/putamen and cerebellar regions. The present data indicate the synthesis of 5-HT1A receptors both in raphe serotonergic cells and anatomically specific serotonergic projection areas, further supporting both a presynaptic autoregulatory and postsynaptic modulatory role for this receptor in serotonergic transmission.

Serotonin Shifts First-Spike Latencies of Inferior Colliculus Neurons

“…How serotonin would alter the representation of such behaviorally important stimulus features is unclear, primarily because we did not observe systematic changes in latency within any functionally distinct group of neurons, such as neurons with particular control latencies. This is likely to reflect the diverse roles of serotonin, acting through multiple receptor types, within the IC (Chalmers and Watson, 1991;Pompeiano et al, 1992 Latency may also encode features of sensory stimuli such as frequency or intensity, making the fact that, in some neurons, serotonin altered spike timing independently of other response properties, an intriguing feature of our results. For example, for the neuron in Figure 11 B, serotonin lengthened latencies but did not change spike count at low but not high frequencies within the receptive field of the neuron.…”

Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease

“…5-HT1A-Rs are expressed on pyramidal neurons in the hippocampus (Chalmers and Watson, 1991;Clement et al, 1996;Khawaja, 1995;Kia et al, 1996aKia et al, , 1996bRaurich et al, 1999;Wright et al, 1995) where they exert an inhibitory action (Corradetti et al, 1998). 5-HT1A-R knockout mice display signs of hippocampal hyperexcitability (Sibille et al, 2000) and Tsetsenis et al found that inhibition of cells within the dentate gyrus subregion of the hippocampus was sufficient to normalize the abnormal fear bias in the knockouts (Tsetsenis et al, 2007).…”

Increased Serotonin-1A (5-HT1A) Autoreceptor Expression and Reduced Raphe Serotonin Levels in Deformed Epidermal Autoregulatory Factor-1 (Deaf-1) Gene Knock-out Mice

“…The serotonin-1A (5-HT1A) somatodendritic autoreceptor inhibits the firing of raphe serotonin neurons to negatively regulate the serotonin system (4). Postsynaptic 5-HT1A receptors are strongly expressed in limbic and cortical brain regions (6,7) and mediate serotonin action to reduce fear and anxiety. 5-HT1A-null mice display increased anxiety behaviors (8 -10) and lack response to SSRI treatment (11), whereas transgenic overexpression of the 5-HT1A receptor decreases anxiety (12).…”