New insights into the relationship of neurogenesis and affect: tickling induces hippocampal cell proliferation in rats emitting appetitive 50-kHz ultrasonic vocalizations

Adult hippocampal cell proliferation (HCP) has been associated with psychopathology, especially depression. However, it is controversial whether a constitutively low rate of HCP is a trait predisposing an individual to psychopathology or whether HCP varies with the subject's affective state. We made use of a so far neglected measure of affect, namely ultrasonic vocalizations, to gain new insights into the relationship of HCP and affect. Rats emit distinct types of ultrasonic vocalizations, which serve as situation-dependent affective signals. In appetitive situations, rats produce 50-kHz-calls, whereas 22-kHz-calls occur in aversive situations. We applied a standardized protocol of repeated tickling and assessed tickling-induced ultrasonic vocalizations as an index of the animals affect. Stereological quantifications of 5-bromo-2′-deoxyuridine (BrdU) and proliferating-cells-nuclear-antigen (PCNA) immunolabeled cells were used to estimate the rate of cell proliferation in the subventricular zone and the subgranular zone of the dentate gyrus in the hippocampus. The rate of cell proliferation was compared between the groups of tickled vs. non-tickled rats and between subgroups of tickled rats defined by the effect of tickling on ultrasonic vocalizations. Tickling induced ultrasonic vocalizations in a subject-dependent manner. HCP correlated positively with appetitive 50-kHz-calls, but negatively with aversive 22-kHz-calls in individual animals, while cell proliferation in the subventricular zone was not associated with the emission of ultrasonic vocalizations. Repeated tickling did not change HCP in all rats, but increased HCP in the subgroup of rats, which experienced this procedure as appetitive, i.e. in rats emitting high numbers of 50-kHz-calls or low numbers of 22-kHz-calls. Together, these data indicate that the effect of tickling on HCP depends on an interaction between a predisposing trait and stimulation-dependent variations of the subject's affective state.