br Conclusion br Acknowledgements br Introduction Aminobutyr

Conclusion
Acknowledgements
Introduction γ- Aminobutyric T0901317 (GABA) is the main inhibitory neurotransmitter in the adult central nervous system. GABA receptors are divided into two classes, GABAA and GABAB. GABAA is an ionotropic receptor that mediates fast GABA responses by opening the Cl¯ channel, while the metabotropic GABAB receptor causes slower GABA responses via G-proteins and secondary messengers (Bettler and Tiao, 2006; Bowery, 2006; Couve et al., 2000; Kornau, 2006; Ulrich and Bettler, 2007). Structurally, GABAA receptors are heteropentameric transmembrane receptors consisting of several subunits from families α, β, γ, δ, ε, π and θ (Mehta and Ticku, 1999). In the hippocampus the principal subunits are α1, α2, α5, β3, γ2 that mostly consist of two α, two β, and one γ that are arranged around a central canal. Particularly, α subunit plays an important role in determining the affinity for GABA (Barnard et al., 1998). GABAB receptors are metabotropic receptors that consist of two subunits, GABAB1 and GABAB2 (López‐Bendito et al., 2004). It has been reported that GABAB1 is required in all functional GABAB receptors (Pagano et al., 2001; Prosser et al., 2001) so that inactivated GABAB1 gene removes the GABAB responses; hence, GABAB1 is a necessary component of GABAB receptors (Prosser et al., 2001; Schuler et al., 2001). It has been demonstrated that the GABAergic neurons mature faster than the glutamatergic excitatory neurons (Ben-Ari et al., 2007), and GABA is the major excitatory neurotransmitter before the maturation of glutamatergic synapses (Khazipov et al., 2001; Tyzio et al., 1999).Hence, in this period, GABA receptorsmediate depolarization. This depolarization activates calcium sensitive signaling processes that are necessary for DNA synthesis, proliferation, migration, and neuronal differentiation during brain development (Galanopoulou, 2008). Given these effects, it has been stated that the GABA receptors in hippocampal cells could regulate neuronal development through the modulating of intracellular calcium (López‐Bendito et al., 2004). Therefore, GABA receptors have an important role in neuronal plasticity underlying learning and memory (Benke, 2010). Thus, it seems that the expression of GABA receptors is prominent at the time and regions where neurogenesis persisted, such as hippocampus during the first two postnatal weeks (Ge et al., 2015; Humphrey, 1967; Rice and Barone, 2000). Hippocampus is a key region for memory consolidation, a mechanism which is very important for learning and memory (Lotfi et al., 2016). GABAergic neurons in the septo-hippocampal system may play an important role in this process (Dalrymple-Alford, 1994; Izquierdo and Medina, 1995). The development of the hippocampus is a multistep process under the guidance of a complex program, and several studies suggested the laterality in hippocampus development in terms of volume, morphology, and cell genesis (Förster et al., 2006; Hami et al., 2014; Hami et al., 2012; Humphrey, 1967; Ragbetli et al., 2002; Thompson et al., 2008). Four main regions have been identified for the hippocampus, CA1, CA2, CA3, and dentate gyrus (DG) that differ in terms of efferent-afferent, major cell types (Knowles, 1992), neurogenesis (Ormerod et al., 2008; Pawluski et al., 2009), and synaptic plasticity mechanism (Hussain and Carpenter, 2005; McBain, 2008). Accordingly, we hypothesized that the expression of GABA receptors, which begins at the embryonic period in rats (Haydar et al., 2000; Lauder et al., 1986), may be one of the main factors contributing to the regulation of developmental and cognitive functions in the developing hippocampus. Moreover, it may also cause laterality differences in this brain structure. Hence, the present study was designed to investigate the developmental regulation and laterality differences of GABAAα1 and GABAB1 receptor subunits expression in the developing rat hippocampus at postnatal day (P) 0, 7 and 14 using real-time PCR, western blot analysis, and immunohistochemistry.