Developing neural networks follow common trends such as expression of spontaneous, recurring activity patterns, and appearance of neuromodulation. How these processes integrate to yield mature, behaviorally relevant activity patterns is largely unknown. We examined the integration of serotonergic neuromodulation and its role in the functional organization of the accessible locomotor network in developing zebrafish at behavioral and cellular levels. Locally restricted populations of serotonergic neurons and their projections appeared in the hindbrain and spinal cord of larvae after hatching (approximately day 2). However, 5-HT affected the swimming pattern only from day 4 on, when sustained spontaneous swimming appeared. 5-HT and its agonist quipazine increased motor output by reducing intervals of inactivity, observed behaviorally (by high-speed video) and in recordings from spinal neurons during fictive swimming (by whole-cell current clamp). 5-HT and quipazine had little effect on the properties of the activity periods, such as the duration of swim episodes and swim frequency. Further, neuronal input resistance, rheobasic current, and resting potential were not affected significantly. The 5-HT antagonists methysergide and ketanserin decreased motor output by prolonging the periods of inactivity with little effect on the active swim episode or neuronal properties. Our results suggest that 5-HT neuromodulation is integrated early in development of the locomotor network to increase its output by reducing periods of inactivity with little effect on the activity periods, which in contrast are the main targets of 5-HT neuromodulation in neonatal and adult preparations.

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The neurohypophysial peptide arginine vasotocin, and its mammalian ortholog arginine vasopressin, influence a wide range of physiological and behavioral responses, including aspects of sexual and social behaviors, osmoregulation, stress response, metabolism, blood pressure, and circadian rhythms. Here, we demonstrate that, in zebrafish (Danio rerio), the vasotocin precursor gene arginine vasotocin-neurophysin (avt) is expressed in two domains in the developing embryo: the dorsal preoptic area and the ventral hypothalamus. In the dorsal preoptic area, avt-expressing cells are intermingled with isotocin-neurophysin (ist) -expressing cells, and these neurons project to the neurohypophysis (posterior pituitary). In the dorsal preoptic area, the transcriptional regulators orthopedia b (otpb) and simple-minded 1 (sim1) are required for expression of both avt and ist. In contrast, otp and sim1 are not required for avt expression in the ventral hypothalamus. Thus, the development of these two avt expression domains is influenced by separate gene regulatory networks. Developmental Dynamics 237:995-1005, 2008.

No abstract