Effects of temperature and neuroactive substances on hypothalamic neurones in vitro: Possible implications for the induction of fever

This paper reviews some of our findings which have shown the usefulness of in vitro methods in the study of hypothalamic neurones. (1) membrane current analyses of dispersed neurones of the rat preoptic and anterior hypothalamus (POA) during thermal stimulation have revealed that warm-sensitive neurones are endowed with a non-inactivating Na⁺ channel having a high Q₁₀ in the hyperthermic range (35-41 °C). (2) A brain slice study has shown that neurones in the organum vasculosum lamina terminalis (OVLT) region have much higher sensitivity to PGE₂ than POA neurones. This provides further evidence of a critical role of the OVLT in translation of blood-born cytokine signals into brain signals for fever induction. (3) Local application of IL-1β and IFNα altered the activity of thermosensitive (TS) neurones and glucose responsive (GR) neurones in vitro in an appropriate way to produce fever and anorexia. While the responses to IL-1β required the local release of prostaglandins, the responses to IFNα were found to be mediated by opioid receptor mechanisms. (4) The responses of POA TS neurones and VMH GR neurones to IL-1β but not those to IFNα, were reversibly blocked by αMSH, an endogenous antipyretic peptide. Thus, immune cytokines and their related neuroactive substances may affect hypothalamic TS and GR neurones thereby producing elaborately regulated changes in homeostatic functions such as thermoregulation (fever) and feeding (anorexia), which are considered as host defence responses.