Electrophysiology of the Anterior Hypothalamus: Thermoregulation and Fever

Abstract

The neural control of body temperature has been studied using the various techniques available to neurobiologists, each of which contributes a particular body of data. Lesioning techniques delineate the central nervous system (CNS) areas whose integrity is important for proper thermoregulation; stimulation studies (physiological, electrical, or chemical) reveal the outputs generated by various CNS areas or sensitive neuronal populations functioning in thermoregulation. Electrophysiological techniques supply detailed information on the activities of neurones in the CNS which are presumed to act in thermoregulation, and to be acted upon by the physical (temperature) and chemical (hormones, transmitters, pyrogens) agents that drive or modify the function of the system.In its capacity as a thermoregulator, the CNS serves two distinct, but overlapping, functions: an integrative one, generating appropriate regulatory effector output (vasomotor, sudomotor, somatomotor, respiratory, etc.) on the basis of a variety of inputs (skin and central temperatures, state of arousal, exercise); and a receptor function, monitoring brain temperature at several sites, thus providing some of the inputs to which the integrator responds. These two functions are in some instances sub served by the same anatomical regions (e.g. anterior hypothalamus and preoptic area). One of the goals of electrophysiological recording studies is to determine if these two functions can be mediated by the same neurone. The characterization of central neurones serving thermoregulatory functions into detectors and integrators (interneurones) has been a major thrust of such studies.The integrative functions of the CNS in thermoregulation have been studied by lesioning techniques and electrical and chemical stimulations (HENSEL 1973). The presence of thermodetectors in the brain has been demonstrated by applying moreor-less localized thermal stimulation to CNS structures. That rostral brain-stem areas contained thermodetectors capable of generating appropriate regulatory outputs, when stimulated by local temperature changes, was demonstrated by the early work of KAHN (1904), BARBOUR (1912) and HAMMOUDA (1933. The sensitive area was localized to the preoptic anterior hypothalamic area (POjAH) in anaesthetized cats by MAGOUN et al. (1938) and by HAMMEL et al. (1960) and Fusco et al. (1961) in unanaesthetized dogs.It has since been demonstrated that other CNS areas will respond to their own temperature; thermal stimulation of the medulla (LIPTON 1973) and of the spinal cord (SIMON 1974) will produce appropriate regulatory activity. Some reports indicate that the mid-brain is also sensitive to its own temperature (CABANAC and A. S. Milton (ed.), Pyretics and Antipyretics

Evidence that cyclic nucleotides are not mediators of fever in rabbits

“…) in rabbits produces mixed hypo-and hyperthermic effects (Duff et al, 1972;Philipp-Dormston & Siegert, 1975) but these complex responses may be the results of db cyclic AMP affecting numerous sites in the CNS after its introduction into the cerebral ventricles. After local application to the preoptic/anterior hypothalamic nuclei (PO/AH), which contain neurones sensitive to both temperature and pyrogens (Eisenman, 1982), db cyclic AMP produces only sustained hyperthermia in rabbits (Woolf et al, 1975;Willies et al, 1976). This observation gives substantial support to the proposal by Rosendorff (1976) that endogenous cyclic AMP is involved in the neurochemical events mediating fever.…”

Thermoregulation and Sleep

“…, one may be more sensitive to IL‐1 than TNF, whereas another may be more responsive to TNF 28 . Cytokines also induce changes in thermosensitivity in POAH neurons; 29 whether SA‐WSNs are uniquely or differentially sensitive to somnogenic cytokines is unknown. Although the investigation of these neurons offers an approach to link thermo‐ and sleep regulation at the cellular level, there are thorny theoretical issues in need of resolution.…”