Expression of GABAA receptor α3-, θ-, and ε-subunit mRNAs during rat CNS development and immunolocalization of the ε subunit in developing postnatal spinal cord

Abstract

Ionotropic GABA A receptors are heteromeric structures composed of a combination of five from at least 16 different subunits. Subunit genes are expressed in distinct cell types at specific times during development. The most abundant native GABA A receptors consist of α1-, β2-, and γ2-subunits that are co-expressed in numerous brain areas. α3-, θ-, And ε-subunits are clustered on the X chromosome and show striking overlapping expression patterns throughout the adult rat brain. To establish whether these subunits are temporally and spatially co-expressed, we used in situ hybridization to analyze their expression throughout rat development from embryonic stage E14 to postnatal stage P12. Each transcript exhibited a unique or a shared regional and temporal developmental expression profile. The thalamic expression pattern evolved from a restricted expression of ε and θ transcripts before birth, to a θ and α3 expression at birth, and finally to a grouped ε, θ and α3 expression post-partum. However, strong similarities occurred, such as a grouped expression of the three subunits within the hypothalamus, tegmentum and pontine nuclei throughout the developmental process. At early stages of development (E17), ε and θ appeared to have a greater spatial distribution before the dominance of the α3 subunit transcript around birth. We also revealed expression of α3, θ, and ε in the developing spinal cord and identified neurons that express ε in the post-natal dorsal horn, intermediolateral column and motoneurons. Our findings suggest that various combinations of α3-, θ-and ε-subunits may be assembled at a regional and developmental level in the brain. Keywordsneuroepithelium; cortex; hindbrain; motoneurons; intermediolateral columnThe physiological actions of GABA, the major inhibitory neurotransmitter in the adult CNS, are mediated by the activation of ionotropic and metabotropic receptors (Sieghart, 2000). Ionotropic GABA A receptors are heteropentameric structures generated by coassembly of α1-6, β1-3, γ1-3, ε, θ and π subunits (Sieghart, 1995;Hevers and Luddens, 1998). Many studies have demonstrated that the subunit composition determines both functional

Gonadal hormone‐independent sex differences in GABAA receptor activation in rat embryonic hypothalamic neurons

“…Considering the responses recorded using allosteric modulators, as well as by expression profiles previously published (Laurie et al, 1992; Pape et al, 2009), we conclude that both male and female hypothalamic neurons possess a large variety of functional GABA A receptors (Figures 5 and 6; Johnston, 1996; Korpi et al, 2002; Olsen & Sieghart, 2008). From our data, we would hypothesise the coexistence of several populations of hypothalamic neurons in culture, an observation also supported by the high variation of GABA‐mediated responses (even within each sex).…”

Von Economo neurons are part of a larger neuronal population that are selectively vulnerable in C9orf72 frontotemporal dementia

“…The findings of this study have impact on the therapeutic intervention of bvFTD. GABRQ is expressed in other regions of the brain, including hypothalamus, amygdala and brainstem structures such as periaqueductal grey and locus coeruleus . Possible subunit assembly partners of GABRQ have been studied in rat locus coeruleus where GABRQ is reported to be co‐expressed with GABRE .…”

mRNA and protein expression for novel GABAA receptors θ and ρ2 are altered in schizophrenia and mood disorders; relevance to FMRP-mGluR5 signaling pathway

“…29 In rat, GABRθ mRNA has been shown embryonically (E17/E19) to localize to the hypothalamus, tegmentum, pontine nuclei and medulla, suggesting a possible role in midbrain development. 30 GABRθ mRNA is expressed in multiple brain regions in human including amygdala, dorsal raphe, hippocampus, hypothalamus, locus coeruleus and substantia nigra. 31 The locus coeruleus is relevant to psychiatric disorders, as it is the largest noradrenergic nucleus and has important roles in the regulation of anxiety states, vigilance, attention and memory functions.…”

“…31 The functional properties of GABA A receptors that include the θ subunit have not been well characterized. 30 …”