Delayed acquisition of schedule-induced polydipsia in rats with zona incerta lesions

Rats with lesions of the zona incerta (ZI) were hypodipsic under free-feeding conditions and were adipsic during periods of food deprivation. Lesioned rats did not differ from controls in daily food intake. In schedule-induced polydipsia (SIP) tests conducted by reducing the rats to 80% of free-feeding body weight and delivering 45 mg Noyes pellets on a fixed-time 1-min schedule, ZI lesions significantly delayed the acquisition of SIP. Both the size and frequency of post pellet drinking bouts were affected by the lesions. After 26 SIP sessions lesioned rats were drinking at levels similar to controls.     

Responses to dietary adulterations in rats with zona incerta lesions

Large lesions of the rostral zona incerta (ZI) permanently reduced food and water intake and body weight to about 75% of control levels. When quinine hydrochloride was added to the water supply, the experimental animals exhibited a somewhat greater initial decrease in fluid consumption, but otherwise responded much like control rats to quinine adulteration of both food and water. The ZI animals reduced their fluid intake when water was added to the food supply, in the form of wet mash, while the controls showed no compensation for the auxiliary water. When presented with sucrose solutions, the ZI animals increased their fluid intake, but reduced their mash consumption, to a greater degree than control rats. The experimental animals also showed an exaggerated response in both food and caloric intake to the addition of sucrose to the wet mash.     

Responsiveness to 2-deoxy-D-glucose and insulin in rats with rostral zona incerta lesions

Lesions of the rostral zona incerta (ZI) impaired or abolished the feeding response to a broad range of doses of 2-deoxy-D-glucose (2DG) (50 to 900 mg/kg), including some that were clearly subthreshold in controls as well as others that induced severe side effects. Most lesioned rats did not increase food intake after any dose of 2DG. Experimental animals that did respond to 2DG consistently are less than controls at all doses. There was no evidence of a lateral shift in the dose-response curve for these rats. In contrast, ZI lesions had little effect on the feeding response to a broad range of doses of insulin (0.5 to 7 units); the dose-response curve of lesioned subjects was essentially parallel to that of controls. A correlational analysis indicated that the relatively minor effects of ZI lesions on the feeding response to insulin but not the devastating impairment of the response to 2DG may be related to the transient debilitating effects that ZI lesions had on postsurgical ad lib intake and body weight.     

Regulation of calorie intake in rats with rostral zona incerta lesions: effects of caloric density or palatability of the diet

Following an initial period of hypophagia, the body weights of rats with zona incerta lesions approached asymptotic levels that were significantly lower than those of controls although daily food intake was not reliably depressed. In spite of persisting deficits in feeding efficiency, the ad libitum food intake of the ZI-lesioned rats (relative to body weight) recovered to preoperative levels and was regulated accurately with respect to the caloric density of the diet. However, rats with ZI lesions were finicky eaters and did not maintain stable calorie intake when given unpalatable diets. The water intake of ZI-lesioned rats remained consistently below that of neurologically intact rats but was normal relative to their own food intake and lowered body weight.     

A Golgi study on the zona incerta of the mouse

Summary The zona incerta (ZI) of the mouse was studied by the rapid Golgi method. In the ZI, small and medium-sized neurons were recognized. The former were the main constituents; their soma were fusiform or piriform in shape (15.5×22 m) and had 4 to 8 primary dendrites. Dendrites of the small neurons in the regions near the ventral and dorsal margins of the ZI ran medially and laterally along the margins of the ZI. The mediumsized neurons were seen in the central ZI portions at the caudal levels of the ZI; they had polygonal or fusiform cell bodies (25×31 m) which emitted 5 to 9 primary dendrites. Some dendrites of the ZI neurons extended into the ventral lateral geniculate nucleus (LGNv), the nucleus of the field of Forel (FF), the cerebral peduncle and the internal capsule. On the other hand, some dendrites of neurons in the LGNv and FF extended into the ZI. Most axons of the ZI neurons coursed dorsally, and some of them could be traced into the medial lemniscus or the dorsal thalamus. A few neurons in the regions near the ventral margin of the ZI sent axons ventrally into the cerebral peduncle.Afferent fibers to the ZI were traced from the cerebral peduncle, internal capsule, field H₁, medial lemniscus and dorsal thalamus. Collaterals of fibers in the Meynert's commissure and field H₂ entered the ZI. Fibers passing through the LGNv also entered the ZI. Additionally, terminal collaterals were observed to arise from fibers running mediolaterally in the ZI. Some fibers were found to send terminals commonly to the ZI, FF and LGNv by way of axon collaterals.     

Impaired feeding responses to intragastric, intraperitoneal, and subcutaneous injections of 2-deoxy-D-glucose in rats with zona incerta lesions

Rats with rostromedial zona incerta lesions displayed severely attenuated feeding responses to intragastric injections of 750, 1000, or 1250 mg/kg of 2-deoxy-D-glucose (2-DG) which elicited optimal feeding and few debilitating side effects in neurologically intact controls. Rats with ZI lesions also ate little, if at all, in response to low doses (200 and 300 mg/kg) of 2-DG administered subcutaneously which were approximately as effective in controls as the intragastric injections of much larger doses. The experimental animals also responded poorly to a standard (600 mg/kg) intraperitoneal (IP) injection of 2-DG but showed only a small impairment in responding to 8 Units/kg of insulin. These results suggest that less stressful routes of administration do not ameliorate the ZI rat's severe deficit in responding to 2-DG that has been reported after IP injections of large doses of the compound, and replicate the observation that insulin feeding is impaired relatively little if at all.     

Parametric study of the regulatory capabilities of rats with rostromedial zona incerta lesions: Responsiveness to hypertonic saline and polyethylene glycol

Rats with lesions in the dorsomedial zona incerta (ZI): (1) were hypodipsic; (2) drank little or nothing during periods of food deprivation; (3) drank little or nothing after injections of 5 ml of 0.50 M, 0.75 M, 1.0 M or 2.0 M NaCl solutions (some animals displayed delayed responses to the highest dose, 6 and 24 hr after the injection); (4) drank normal quantities of water or saline after 5 ml of 15%, 20%, or 30% PG (half of the animals that had shown absent or severely impaired responses to hypertonic saline; the other half did not drink saline or water in response to any dose of PG except the highest—5 ml of 30%); (5) sharply reduced or abolished sodium appetite; (6) reduced or abolished the feeding response to 2-DG without affecting ad lib food intake. Similar effects on 2-DG eating and sodium appetite (but not on water intake under ad lib or food-deprivation conditions, or on drinking in response to hypertonic saline or PG) were produced by lesions in ventral thalamus or dorsomedial hypothalamus.     

Loss of feeding in response to 2-deoxy-D-glucose but not insulin after zona incerta lesions in the rat

Bilateral lesions in the anterior aspects of the zona incerta of male rats reliably reduced the feeding response to systemically administered 2-deoxy-D-glucose. Insulin-induced feeding remained intact. Zona incerta lesions may interrupt central vagal projections important for the feeding response to cellular glucoprivation.     

Electrolytic lesions and knife cuts in the region of the zona incerta impair sodium appetite

Bilateral lesions in the anterior zona incerta of male rats produced reliable impairments of need-related sodium appetite which were more severe than those seen after bilateral lesions in the thalamic gustatory nucleus. Horizontal knife cuts dorsal to the zona incerta, separating it from the ventral thalamus, seemed to reproduce the effects of thalamic lesions on sodium appetite. Horizontal knife cuts ventral to the zona incerta, separating it from the hypothalamus, produced a greater reduction in sodium intake than did the dorsal knife cuts. Neural pathways that might mediate regulatory sodium intake were discussed.     

Reinnervation of dopamine neurons by regenerating serotonin axons in the rat medial zona incerta

Summary Cellular relationships between serotonin (5-HT) axons and tyrosine hydroxylase (TH)-containing neurons were examined by combined (³H)5-HT uptake radioautography and TH immunocytochemistry in the medial zona incerta (ZI) of adult rats, 7 and 50 days after an intracerebral injection of 5,7-Dihydroxytryptamine (5,7-DHT). Seven days post-lesion, only rare, scattered (³H)5-HT-labeled axon terminals were apparent in the zone of the medial ZI accessible to intraventricularly injected (³H)5-HT. In contrast, in sham-injected animals (³H)5-HT-labeled varicosities were numerous and often observed adjacent to TH-immunoreactive perikarya and dendrites. Fifty days post 5,7-DHT injection, the density of (³H)5-HT-labeled terminals approximated that seen in sham-treated animals. At the ultrastructural level, these regenerated 5-HT axons were similar in size, shape and content to those observed in sham-operated rats. Also, as in sham, some of the (³H)5-HT-labeled axons were directly apposed to TH-immunopositive labeled profiles. The latter included large dendritic shafts and dendritic spines, but only rare perikarya. In both sham- and 5,7-DHT-treated animals a few of the contacts between (³H)5-HT-labeled and TH-immunoreactive profiles exhibited an asymmetric synaptic differentiation. These results indicate that 5-HT fibers in the medial ZI, following regeneration, can reestablish normal relationships and even synapses with a given population of chemically identified cells.     

Circadian rhythms in ingestive behavior and responsiveness to glucoprivic and osmotic challenges in rats with rostral zona incerta lesions

Albino rats with lesions in the rostral zona incerta (ZI) displayed an exaggerated diurnal rhythm of ingestive behavior, consuming nearly all of their daily food and water during the dark portion of a 12-hr light/12-hr dark cycle. When tested during the light phase of the cycle, rats with ZI lesions ate little or nothing in response to 2-deoxy-D-glucose (2DG) while their response to insulin was only slightly impaired. When these tests were repeated during the dark phase of the cycle, the response to insulin was entirely normal but the response to 2DG was even more depressed than during daytime testing. During the light phase of the cycle, rats with ZI lesions also drank little or nothing in response to hypertonic saline. This impairment was ameliorated in some but not all experimental rats when these tests were repeated in the dark. A correlational analysis failed to establish a significant relation between changes in the diurnal distribution of ad lib food and water intake and feeding responses to 2DG or insulin or drinking responses to hypertonic saline in the light or dark phases of the cycle.     

Zona incerta lesions: regulatory drinking deficits to intravenous NaCl, angiotensin, but not to salt in the food

Rats with bilateral damage to the anterior zona incerta (ZI) showed small and delayed drinking responses after IP hypertonic NaCl injection, but they normally excreted most of the salt load within 6 hr. The impaired drinking responses were also evident after nonpainful intravenous (IV) NaCl infusions. After nephrectomy, rats with complete ZI lesions did not drink within 24 hr of the NaCl infusion. Rats with less complete lesions showed reduced and delayed drinking. In contrast to these profound osmoregulatory drinking impairments, all of the lesioned rats increased their water to food ratio when fed a 3% NaCl-supplemented diet. ZI lesioned rats did not drink in response to IV infusions of angiotensin II. The role of the ZI in drinking behavior is discussed in terms of the paradigm-dependent nature of these results, and parallels with other findings are considered.     

Zona incerta lesions: disruption of regulatory water intake

Bilateral lesions in the anterior aspects of the zona incerta of male rats produced adipsia. When tested under ad lib access to dry laboratory chow and water, only a small, although statistically reliable, decrease in water intake occurred. However, water intake promptly fell to zero when food was removed, suggesting that drinking occurred not in response to physiological signals which regulate water intake, but only as a means of facilitating the ingestion of dry food.     

Deficits in passive avoidance and fear behavior following bilateral and unilateral amygdala lesions in mice

Bilateral amygdala lesions severely disrupt passive avoidance and fear behaviors. The effects of unilateral amygdala lesions on these behaviors are unclear, though unilateral lesions in other structures produce deficits similar to those produced by bilateral lesions. In the present experiment, female mice with unilateral or bilateral amygdala lesions manifested similar patterns of passive avoidance and fear behavior deficits. The results are discussed in light of previous passive avoidance and unilateral lesion studies.     

Structural organization of the zona incerta of the dog diencephalon

Studies performed using the Nissl and Kluver-Barrera methods for analysis of the organization of fibers, morphological neuron types, and neuron density distribution were undertaken to map the zona incerta of the diencephalon of the dog brain; five individual sectors were identified, whose boundaries were further identified by histochemical detection of NADPH-diaphorase-positive neurons.     

The anatomy of the caudal zona incerta in rodents and primates

The caudal zona incerta is the target of a recent modification of established procedures for deep brain stimulation (DBS) for Parkinson's disease and tremor. The caudal zona incerta contains a number of neuronal populations that are distinct in terms of their cytoarchitecture, connections, and pattern of immunomarkers and is located at a position where a number of major tracts converge before turning toward their final destination in the forebrain. However, it is not clear which of the anatomical features of the region are related to its value as a target for DBS. This paper has tried to identify features that distinguish the caudal zona incerta of rodents (mouse and rat) and primates (marmoset, rhesus monkey, and human) from the remainder of the zona incerta. We studied cytoarchitecture, anatomical relationships, the pattern of immunomarkers, and gene expression in both of these areas. We found that the caudal zona incerta has a number of histological and gene expression characteristics that distinguish it from the other subdivisions of the zona incerta. Of particular note are the sparse population of GABA neurons and the small but distinctive population of calbindin neurons. We hope that a clearer appreciation of the anatomy of the region will in the end assist the interpretation of cases in which DBS is used in human patients.     

Connections of the zona incerta to the reticular nucleus of the thalamus in the rat

This study demonstrated that there is a pathway from the zona incerta to the thalamic reticular nucleus. Injections of horseradish peroxidase or Fluorogold were made, using stereotaxic coordinates, into the rostral, intermediate or caudal regions of the thalamic reticular nucleus of adult Sprague-Dawley rats. The results show that the different regions of the thalamic reticular nucleus have distinct patterns of connections with the sectors of the zona incerta. In terms of the relative strength of the connections, injections made into the rostral regions of the thalamic reticular nucleus showed the highest number of labelled cells within the rostral and ventral sectors of the zona incerta; injections made into the intermediate regions of the thalamic reticular nucleus showed labelled cells in the dorsal and ventral sectors; while injections to the caudal regions of the thalamic reticular nucleus showed only a few labelled cells in the caudal sector of the zona incerta. Previous studies have shown that the zona incerta projects to the higher order thalamic nuclei but not first order thalamic nuclei. The labelling observed in the present study may represent collaterals of zona incerta to higher order thalamic nuclei projections.     

Projections of the basal ganglia to the zona incerta of the dog diencephalon

Retrograde axonal transport of horseradish peroxidase was used to show that the projections of the globus pallidus, entopeduncular nucleus, substantia nigra, and pedunculopontine tegmental nucleus in dogs are directed to all segments of the zone incerta. The experiments reported here identified no topical features in the organization of these projections in dogs, as application of marker to different areas of the zona incerta yielded similar distributions of labeled neurons in the basal ganglia. No striatal projections to the zone incerta were found.     

Influences of bilateral hippocampal lesions upon kindled amygdaloid convulsive seizure in rats

In this study, rat hippocampus was lesioned bilaterally after completion of amygdaloid kindling, to examine how hippocampus affects the kindling permanency. The ventral hippocampal lesions of the kindled rats inhibited reappearance of any kindled seizures. The other rats with the same lesions showed the regression of generalized convulsion. These results suggest that hippocampus, especially ventral parts of hippocampus, would have rather facilitatory or maintaining influence on the kindled neural circuits, relating to the catecholaminergic system in rat forebrain.     

Regulatory and secondary water intake in rats with lesions of the zona incerta.

Bilateral electrolytic lesions of the zona incerta (ZI) permanently reduced daily water intake of rats by 20-30%. Lesioned rats did not differ from controls in daily food intake, body weight, hematocrit, or serum osmolality, Na+ or K+ levels. The hypodipsia was not caused by changes in water requirements or excretory function or by a nonspecific depression of behavior. Compensatory reductions in water losses maintained fluid balance. Lesioned rats drank as much water as controls in response to intracellular and extracellular dehydration, but unlike controls, appeared to restrict their daily water intake to these regulatory responses. Lesions of the ZI attenuated the ingestion of extra water observed when rats were maintained on a liquid diet adequate to meet fluid requirements, and daily water intake of lesioned but not control rats closely followed changes in water needs. It was concluded that lesions of the ZI reduce daily water intake towards minimal requirements for fluid balance by attenuating secondary drinking (drinking independent of water needs for fluid homeostasis.