Diversity of oxytocin neurones: Beyond magno- and parvocellular cell types?

The hypothalamic neuropeptide oxytocin (OT), which is evolutionarily conserved among different species throughout the animal kingdom, is a key modulator of a variety of socio-emotional behaviours such as fear, trust and empathy. OT cells in the mammalian hypothalamus have been traditionally divided into two distinct types: agnocellular (magnOT) and parvocellular (parvOT) or preautonomic neurones. This distinction is based on OT cell sizes and shapes, projections, electrophysiological activity and functions. Indeed, although neuroendocrine magnOT neurones are known to primarily project their axons to the posterior pituitary and to a number of forebrain regions, non-neuroendocrine parvOT neurones have been seen as the main source of OT innervation of the brainstem and spinal cord to control autonomic functions and pain perception. However, very recent findings have demonstrated distinct genetic profiles in OT neurones, allowing the discrimination of at least four types of cells expressing OT. Furthermore, unexpected axonal projections of parvOT neurones to the forebrain and magnOT neurones to the midbrain have been newly reported. In this review, we focus on the detailed analysis of methods of distinction between OT cell types, in- and output sites, and morphology, as well as on the direct connectivity between OT neurones and its physiological significance. Finally, we propose a hypothesis suggesting that the central OT system is composed of more than just two OT cell types, which needs to be confirmed by the application of available genetic and anatomical techniques.