Effects of prostaglandin E2 on the electrical properties of thermally classified neurons in the ventromedial preoptic area of the rat hypothalamus

John D Griffin,Heather J Ranels

doi:10.1186/1471-2202-6-14

Abstract

BackgroundPhysiological and morphological evidence suggests that activation of the ventromedial preoptic area of the hypothalamus (VMPO) is an essential component of an intravenous LPS-dependent fever. In response to the endogenous pyrogen prostaglandin E2 (PGE2), the majority of temperature insensitive neurons in the VMPO show an increase in firing rate, while warm sensitive neurons are inhibited. We have hypothesized that these PGE2 dependent effects on firing rate are due to changes in the inherent electrical properties of VMPO neurons, which are regulated by the activity of specific ionic currents.ResultsTo characterize the electrical properties of VMPO neurons, whole-cell recordings were made in tissue slices from male Sprague-Dawley rats. Our results indicate that PGE2 dependent firing rate responses were not the result of changes in resting membrane potential, action potential amplitude and duration, or local synaptic input. However, PGE2 reduced the input resistance of all VMPO neurons, while increasing the excitability of temperature insensitive neurons and decreasing the excitability of warm sensitive neurons. In addition, the majority of temperature insensitive neurons responded to PGE2 with an increase in the rate of rise of the depolarizing prepotential that precedes each action potential. This response to PGE2 was reversed for warm sensitive neurons, in which the prepotential rate of rise decreased.ConclusionWe would therefore suggest that PGE2 is having an effect on the ionic currents that regulate firing rate by controlling how fast membrane potential rises to threshold during the prepotential phase of the action potential.

Highlights

Physiological and morphological evidence suggests that activation of the ventromedial preoptic area of the hypothalamus (VMPO) is an essential component of an intravenous LPS-dependent fever
Through the integration of both central and afferent thermal information, this set-point is established by the activity of neurons in the preoptic and anterior regions of the hypothalamus (PO/ AH) that can be thermally classified on the basis of their inherent ability to respond to changes in temperature [3]
Using the cellularly invasive procedure of whole cell recording, the prostaglandin E2 (PGE2) dependent changes in firing rate that were recorded from VMPO neurons were similar to those reported in an earlier extracellular single-unit recording study [12]

Summary

Introduction

Physiological and morphological evidence suggests that activation of the ventromedial preoptic area of the hypothalamus (VMPO) is an essential component of an intravenous LPS-dependent fever. In addition to responding to local changes in temperature, some of these warm sensitive neurons are responsive to changes in skin or spinal temperature, while others show thermally dependent changes in their firing rates that may directly correlate with the activation of specific thermoregulatory responses. This integrative ability seems to be restricted to warm sensitive neurons in the PO/AH, temperature insensitive neurons may play an important role in determining the setpoint temperature through their synaptic interactions with thermoregulatory effector neurons [3]. Regardless of thermosensitivity, many PO/AH neurons may respond to adjustments in other homeostatic conditions or the presence of endogenous pyrogens such as prostaglandin E2 (PGE2), which could shift the thermostatic set-point and alter the activation of thermoregulatory mechanisms [2]

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Discussion

Conclusion