Hypothalamic Region Facilitating Shivering in Rats.

Abstract

Shivering of skeletal muscle is the main effector response of homeothermic animals to the cold to maintain body temperature. The hypothalamus is of unquestionable importance in the control of shivering [1,2]. The preoptic area in particular functions to monitor local temperature changes. Shivering is elicited when this area is cooled, and it is suppressed when it is warmed [3,4]. Our previous study has indicated that most efferent signals mediating these responses originate in warm-sensitive neurons [1, 2] and descend in the medial forebrain bundle [5]. The posterior part of the hypothalamus also has long been considered to be important for the control of shivering and referred to as the "heat maintenance center" [6]. Lesions in the caudal hypothalamus abolished or impaired shivering, and shivering is invoked by electrical stimulation of this area [1,2]. More exactly designed lesion and stimulation experiments indicated that the dorsomedial region of the posterior hypothalamus is especially important for the production of shivering [7,8]. However, it is unclear whether it is the effects of electrical stimulation and lesioning on cell bodies or simply on axons originating in other brain regions that truly participate in the control of shivering, because both procedures influence cell bodies and passing fibers. The aim of the present study is to examine this question. We tested the effect on shivering activity of an injection of muscimol, a GABA A receptor agonist, into the posterior hypothalamus and adjacent regions in anesthetized rats. Because this chemical affects only the soma and dendrites, we reasoned that if muscimol influenced shivering, neurons that participate in the control of shivering should be found there. MethodsWe used 52 adult male Crj: Wistar rats (350-400 g, Charles River Japan, Yokohama, Japan) from a colony housed at 22°C with free access to food and water. The experiment was approved by the Animal Care Committee of Osaka University Medical School. After anesthesia with urethane (1.4 g/kg, I.P.), each rat was mounted in a stereotaxic apparatus according to the coordinate system of Paxinos and Watson [9]. A stainless steel guide tube (0.5 mm o.d.) was implanted into the hypothalamus 0.3-2.5 mm from the midline, 2.0-5.0 mm behind bregma, and the tip of this tube was 6.0-9.5 mm below the skull surface. In most cases two guide tubes were implanted, one on each Japanese Journal of Physiology Vol. 51, No. 5, 2001 625Japanese Journal of Physiology, 51, 625-629, 2001 Key words: shivering, posterior hypothalamus, dorsomedial hypothalamus. Abstract:Although the posterior part of the hypothalamus has long been considered important for thermoregulatory shivering, it is unknown whether the neurons there or the passing fibers are implicated in the response. Exposure of urethane-anesthetized rats to cold (15-21°C) elicits shivering. An injection of muscimol (0.5 mM), a GABA A receptor agonist, into the medial part of the hypothalamus, including the dorsomedial and posterior nuclei, suppressed the cold-...

Estrogen modulates central and peripheral responses to cold in female rats

“…The VMH and DMH involve iBAT thermogenesis [23,26]. The DMH has been reported to be involved in both shivering and non-shivering thermogenesis [25], and it receives neurons from the MPO [26]. In our study, exposure to cold increased the number of cFos-IR cells in all these areas.…”

“…The PO area is the site which sends many efferent neurons for thermoregulation [23] and also receives afferent neurons for thermoregulation [24]. The PH is involved in shivering thermogenesis [25], and the cold signal from the skin reaches the MnPO [24]. The VMH and DMH involve iBAT thermogenesis [23,26].…”

Central circuitries for body temperature regulation and fever

“…Inhibition of neurons in the DMH with muscimol injections immediately reverses BAT thermogenesis, shivering, and tachycardia evoked by skin cooling or PGE 2 injection into the POA (Fig. 6, A-F) (82,106,107,110,172,189), indicating that these cold-defensive and febrile responses require activation of DMH neurons. Furthermore, antagonizing GABA A receptors in the DMH elicits BAT thermogenesis, cutaneous vasoconstriction and tachycardia (20,134,191).…”

Central neural control of thermoregulation and brown adipose tissue

“…Briefly, cutaneous, and possibly visceral, cold afferent signals excite second-order cold sensory neurons in the spinal and trigeminal dorsal horns which project to thermally-responsive neurons in the LPBel (Nakamura et al, 2008b), as with the activation of other cold-defense effectors. Putative GABAergic interneurons in the MnPO are activated (Nakamura et al, 2008a; Nakamura et al, 2011) to reduce the activity of warm-sensitive, shivering-inhibiting MPA neurons (Zhang et al, 1995; Nakamura et al, 2011), thereby disinhibiting DMH neurons (Tanaka et al, 2001; Nakamura et al, 2011) that project to shivering-promoting premotor neurons in the rRPa providing an excitatory drive (Tanaka et al, 2006; Nakamura et al, 2011) to somatic alpha-motoneurons, and possibly also gamma-motoneurons, in the spinal ventral horn.…”