Parenting-activated GABAergic neurons in the lateral septum and their innervation by thalamic TIP39-fibers
Tuberoinfundibular peptide of 39 residues (TIP39) is a neuromodulator involved in the central control of maternal adaptations. TIP39 is maternally induced in the brain during the early postpartum period and its expression shows the most significant induction in the Posterior intralaminar thalamic nucleus (PIL). In this study we explored the presence of TIP39-containing fibers projecting from the PIL to the ventral lateral septal area by using the injection of the anterograde pathway tracer biotinylated dextran amine in suckling dams. We aimed to determine the function of thalamic TIP39-positive projections in the maternal activation of the septum. We found increased number of activated neurons in lactating mothers and slightly but also significant increased activation in those mothers who were physically separated from their pups compared to control mothers by applying the c-Fos technique. We confirmed the synaptic relationship between c-Fos-activated neurons and TIP39-positive fibers by double immuno-electron microscopy. The connection between TIP39-positive fibers and septal neurons is also presented in a mouse line containing ZsGreen reporter protein in vesicular GABA transporter-expressing neurons. We established that maternally-activated neurons and neurons surrounded by TIP39-positive fibers are both GABAergic in the septum. Moreover, c-Fos-activated neurons are mainly positive for the marker calbindin but not for calretinin. This study highlights the importance of PIL-derived fibers, which innervate septal neurons in lactating mothers and suggests the activation of an inhibitory system affecting parenting mechanisms in response to pup exposure under the control of the lateral septal GABAergic neurons. Grant support: NKFIH-4300-1/2017-NKP_17 (NAP2), NKFIH-OTKA K116538.