Lateral hypothalamic lesions in ground squirrels: rapid recovery and residual deficits.

The effects of lateral hypothalamic (LH) lesions were studied in golden-mantled ground squirrels, Spermophilus lateralis, a species of mammalian hibernator that displays endogenous circannual body weight cycles when kept in constant conditions. The lesions were made during the weight-gain phase. Evidence that the lesions were well placed included interruption of weight gain, transient aphagia, disrupted nest building, increased spillage of food crumbs and in some cases abnormal postures or movement. Despite these deficits most animals survived. Their body weights at the first postoperative peak of the cycle recovered either to within the control range (Experiment 1) or close to preoperative peak levels (Experiment 2). There was no evidence that the lesions lowered set points. The rapid recovery of weight and eating by ground squirrels given only dry rodent chow, after large lesions (1.5-2.5 mA, DC anodal, 15-25 s), contrasts with what is seen in rats following LH lesions.

Colliding of activity onset and offset: evidence for multiple circadian oscillators.

When hamsters, Mesocricetus auratus, are kept in dim light, wheel running at the onset and the offset of their active phase have different circadian periods. As a result, the active phase expands and eventually the two activity components collide. There is then a temporary explosion of activity at a time that was previously in the rest period. This is followed by disorganization of the rhythm or by phase jumps. Such phase jumps probably stem from the interaction of two oscillators with different natural periods rather than from threshold changes for the expression of activity.

Affective disorders and circadian rhythms.

Abnormal circadian rhythms have been associated with affective disorders. A review of this rapidly expanding area of investigation shows that while a clear causal relationship has not yet been proven, a knowledge of the circadian system and its dysfunction can help in understanding unipolar and bipolar depression. Evidence suggests that existing therapies such as lithium and antidepressants act upon the circadian system. Better identification of individuals at risk for affective disorders and the development of new preventive and therapeutic interventions may result from further study of circadian dysfunction.

Electrically induced behavior and neural specificity in ground squirrels and dormice.

Electrical stimulation of the lateral hypothalamus in 2 species of hibernator, dormice (Glis glis) and ground squirrels (Spermophilus lateralis), suggests that induced behaviors may reflect activation of specific neural systems, rather than merely activation of a single central mechanism interacting with internal and external cues and past experience (prepotency hypothesis). In dormice, the stimulation induced feeding on powdered food; in squirrels it induced either feeding or picking up of food pellets. Consistent with neural specificity in both species were high probabilities of emergence (78-81%) of a behavior during stimulation at an electrode site, with no greater ease of emergence at a second site tested. In squirrels, only 1 of the 2 behaviors emerged at a site, and there was independence between behaviors emerging at contralateral sites. Long-term reliability of the behavior initially observed at an electrode site was 100% despite infradian (dormice) or circannual (squirrels) cycles of body weight and food intake. Some squirrels consistently showed different induced behaviors at contralateral electrode sites throughout their circannual cycle. These observations suggest that feral species are valuable in investigations of mechanisms underlying electrically induced behaviors, and that reevaluation of the prepotency hypothesis may be in order.

Neurohumoral stimulation of lipogenesis during altered states of energy balance.

Acid extracts of bovine hypothalamus stimulate lipogenic activity in adipose tissue. We employed a rat fat cell bioassay system to determine whether tissue concentrations of the active material vary as a function of spontaneous alterations in energy balance in hibernators and/or the obesity resulting from bilateral electrolytic lesions of the ventromedial area of the hypothalamus in rats. When hypothalamic extracts and partially purified plasma were fractionated using reverse-phase high-pressure liquid chromatography, both the void volume and material eluting 17 min after the start of a 25-min linear methanol gradient enhanced glucose incorporation into total lipid. Activities eluting with these two fractions were positively correlated with one another and were independent of insulin. The results indicate that a hypothalamic lipogenic factor (LHF) is detectable in plasma, that hypothalamic and circulating LHF concentrations vary in a reciprocal manner, and that elevations in plasma LHF concentration are associated with insulin resistance. The data suggest that the central regulation of lipogenesis is at least partially mediated by a hypothalamic humoral factor reaching fat depots via the circulation.

Ventromedial hypothalamic lesions in rats: gradual elevation of body weight set-point.

Bilateral electrolytic (DC) or radiofrequency (RF) lesions of the ventromedial hypothalamic (VMH) area produced two abnormal stages of fattening in adult female rats. Following a negatively-accelerated, curvilinear phase of weight gain which lasted 10 weeks, a linear phase of fattening continued for an additional 30 weeks at a rate approximately double that of operated control rats of the same age. During this second phase of fattening, lesioned rats were food-restricted between the 20th and 26th weeks postlesion. Compared to the rate of weight gain in the linear phase prior to food restriction, the rate over the same weight range following release from food restriction was significantly greater for both DC and RF-lesioned rats. Furthermore, by the 40th postlesion week, the lesioned rats had approached the weight they would have been if not food restricted. These observations suggest that VMH area lesions induce a gradual climbing of the set-point for body weight which occurs independently of actual food intake or body weight, and which either follows or is superimposed on the immediate elevation of the set-point responsible for the initial, curvilinear phase of weight gain. As a model for human idiopathic obesity, the long-term effect of VMH area lesions may be more important than the immediate effect.