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 Qjo 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-borne cytokine signals into brain signals for fever induction. (3) Local application of IL -1/9 and IFNa 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 -1/9 required the local release of prostaglandins, the responses to IFNa were found to be mediated by opioid receptor mechanisms. (4) The responses of POA TS neurones and VMH GR neurones to IL -1/9 but not those to IFNa, were reversibly blocked by aMSII, 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.
Using brain slices the effect of prostaglandin E2 (PGE2) on neurones from different locations of the rat hypothalamus was analysed. PGE2 (150 ng), when injected into the perfusion chamber, influences all hypothalamic neurones studied. The pattern of firing rate changes after PGE2 is variable, but the depressive effect predominates - 72 % of neurones decrease their firing rate in long-term experiments. PGE2 also lowers the thermosensitivity of warm sensitive neurones and increases the thermosensitivity of temperature insensitive neurones.