Neurogenesis and synaptogenesis during the early stages of development are profoundly influenced by the action of neurotrophic factors, among which the most known are the effects of the brain-derived neurotrophic factor (BDNF). In neuronal cells, the mature isoform of BDNF (mBDNF) is generated by a proteolytic cleavage of its precursor proBDNF (Lin, 2015; Wang et al., 2021).

Both proBDNF and mBDNF are abundantly expressed in the rat hippocampus in the first postnatal week, contributing to the development of neural circuits (Menshanov et al., 2015). The presence of mBDNF and proBDNF forms regulates excitatory glutamatergic and inhibitory gamma aminobutyric acid (GABA)ergic neuronal network activity (Riffault et al., 2018). Recent evidence indicates an interplay between proBDNF signaling and GABA neurotransmission in developing hippocampal neural circuitry (Riffault et al., 2018). Moreover, the mBDNF-TrkB signaling pathways specifically play a role in modulating gamma aminobutyric acid (GABA)ergic neurotransmission within the hippocampal region cornu ammonis 1 (CA1, Porcher et al., 2018). In the context of excitatory neurotransmission, in cultured hippocampal neurons, the expression and distribution of vesicular glutamate transporters were suggested to be regulated by BDNF (Melo et al., 2013).

Although many factors contribute to excitation/inhibition balance during early brain development, neuropeptide oxytocin in particular appears to be involved in the formation of hippocampal circuitry underlying social memory (Raam et al., 2017; Bertoni et al., 2021). Oxytocin receptors are expressed in both excitatory pyramidal neurons and inhibitory interneurons throughout the hippocampus (Meira et al., 2018; Young and Song, 2020). Moreover, it is known that hippocampal oxytocin significantly influences social memory and social recognition (van der Kooij and Sandi, 2012). We have found that neonatal oxytocin administration increases hippocampal BDNF expression in rats (Bakos et al., 2014), which could be associated with changes of cell-adhesion synaptic molecule and scaffolding protein levels observed in response to oxytocin treatment on the 5th postnatal day (Filova et al., 2020). Furthermore, in our other study performed in adult rats, we demonstrated that intracerebroventricular oxytocin application increases the expression of neurotrophins with a corresponding change of short-term hippocampus-dependent memory (Havranek et al., 2015). Although oxytocin clearly contributes to the brain basis of social behaviour, it is currently unknown whether oxytocin affects BDNF levels in the developing hippocampus.

Therefore, the aim of the present study was to evaluate the early developmental effect of oxytocin administration on the expression of 1) BDNF isoforms and 2) GABAergic and glutamatergic markers in the hippocampus. Additionally, we also evaluated the branching of dendrites of primary hippocampal GABAergic and glutamatergic neurons in vitro in response to incubation with oxytocin.