scholarly journals Optogenetic mapping of feeding and self-stimulation within the lateral hypothalamus of the rat

2019 ◽  
Author(s):  
Kevin R. Urstadt ◽  
Kent C. Berridge

AbstractThe lateral hypothalamus (LH) regulates eating and motivation, and includes several anatomical subregions. This study explored localization of function across different LH subregions in controlling food intake stimulated by optogenetic channelrhodopsin excitation, and in supporting laser self-stimulation. We particularly compared the tuberal LH, the posterior LH, and the lateral preoptic area. Local diameters of tissue optogenetically stimulated within LH were assessed by measuring laser-induced Fos plumes and Jun plumes via immunofluorescence surrounding optic fiber tips, and were used to map localization of function for effects elicited by LH optogenetic stimulation. Optogenetic stimulation of the tuberal subsection of the LH behaviorally produced the most robust food intake initially, but produced only mild laser self-stimulation in the same rats. However, after repeated exposures to optogenetic stimulation, tuberal LH behavioral profiles shifted toward more self-stimulation and less food intake. By contrast, stimulation of the lateral preoptic area produced relatively little food intake or self-stimulation, either initially or after extended stimulation experience. Stimulation in the posterior LH subregion supported moderate self-stimulation, but not food intake here, and at higher laser intensity shifted valence to evoke escape behaviors. We conclude that the tuberal LH subregion may best mediate increases in food intake stimulated by optogenetic excitation. However, incentive motivational effects of tuberal LH stimulation may shift toward self-stimulation behavior after repeated stimulation. By contrast, the lateral preoptic area and posterior LH do not as readily elicit either eating behavior or laser self-stimulation, and may be more prone to higher-intensity aversive effects.

1970 ◽  
Vol 22 (2) ◽  
pp. 125-132 ◽  
Author(s):  
J. E. Blundell ◽  
L. J. Herberg

The diencephalic area most sensitive to microinjections of noradrenaline lay outside the area of the lateral hypothalamus in which feeding can be produced by electrical stimulation. Injection of either area, including injections that caused increased feeding, failed to have any effect on hoarding activity. Since hoarding can be elicited both by food deprivation and by electrical stimulation of the lateral hypothalamus, these findings indicate biochemical, anatomical and motivational differences between the central feeding mechanism sensitive to adrenergic stimulation, and that responding to electrical stimulation or nutritional depletion. The former mechanism may be disinhibitory; the latter, excitatory.


1997 ◽  
Vol 273 (1) ◽  
pp. R107-R112 ◽  
Author(s):  
E. R. Gillard ◽  
A. M. Khan ◽  
A. ul-Haq ◽  
R. S. Grewal ◽  
B. Mouradi ◽  
...  

Despite intense study of neurotransmitters mediating hypothalamic controls of food intake, little is known about which second messengers are critical for these mechanisms. To determine whether adenosine 3',5'-cyclic monophosphate (cAMP) might participate in these mechanisms, we injected the membrane-permeant cAMP analog 8-bromo-cAMP (8-BrcAMP) hypothalamically in satiated rats. Injection of 8-BrcAMP (10-100 nmol) into the perifornical (PFH) and lateral hypothalamus (LH) dose dependently stimulated food intake of up to 15.7 g in 2 h. Significantly smaller responses were obtained with thalamic injections. In contrast to the strong stimulatory effects of PFH and LH 8-BrcAMP, cAMP and 8-bromo-guanosine 3',5'-cyclic monophosphate (100 nmol) were ineffective, suggesting a chemically specific, intracellular action. Consistent with this, combined PFH injection of 7-deacetyl-7-O-(N-methylpiperazino)-tau-butyryl-forskolin dihydrochloride and 3-isobutyl-1-methylxanthine, agents that increase endogeneous cAMP, stimulated eating of up to 9.9 g in 2 h. These results demonstrate that increases in PFH/LH cAMP can elicit complex, goal-oriented behavior, suggesting an important role for cAMP in hypothalamic mechanisms stimulating food intake.


2020 ◽  
Vol 18 (2) ◽  
pp. 123-130
Author(s):  
Eugenii R. Bychkov ◽  
Andrei A. Lebedev ◽  
Nikolai S. Efimov ◽  
Artyem S. Kryukov ◽  
Inessa V. Karpova ◽  
...  

The aim was to study the effect of rewarding and aversive stimulation of lateral hypothalamus on the turnover of monoamines in the terminal structures of the mesocorticolimbic and nigrostriatal systems: the nucleus accumbens (NAc) and striatum (St). The Wistar male rats were implanted electrodes in the lateral hypothalamus and further trained in self-stimulation test. Animals were also selected on aversive emotional reactions were observed after pressing the pedal for self-stimulation. Subsequently, forced stimulation was performed for 5 minutes and the animals were decapitated. The content of norepinephrine, dopamine (DA) and its metabolites 3,4-dioxiphenylacetic acid (DOPАС) and homovanilinic acid, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the nucleus accumbens and striatum were determined by high performance liquid chromatography with electrochemical detection. Positive and aversive stimulation of lateral hypothalamus decreased the level of DA in the NAc, however, only stimulation of the positive emotiogenic zone increased the DA and 5-HT turnover in the NAc, as evidenced by an increase in the DOPАС/DA and 5-HIAA/SER ratios, respectively. Rewarding and aversive stimulation decreased the level of 5-HT in St, however, only rewarding stimulation decreased the St level of 5-HIAA compared to control and animals with aversive stimulation. Rewarding stimulation increased the turnover of serotonin in St, as evidenced by the increase of 5-HIAA/5-HT ratios. The activity of the noradrenergic system did not change after rewarding and aversive stimulation. Thus, both rewarding and aversive electrical stimulation increases the turnover of DA and 5-HT in NAc and St. However, these changes are more significant after rewarding stimulation. DA turnover increases more in NAc, and 5-HT turnover in St. The data obtained indicate the specificity of the dopaminergic and serotonergic involvement for the formation of a modality of emotional reactions. Data may provide guidance for developing treatment strategies for neuropsychiatric diseases related to the malfunction of the reward system.


2018 ◽  
Vol 16 (2) ◽  
pp. 37-41
Author(s):  
Nikolay S Efimov ◽  
Yulia N Bessolova ◽  
Inessa V Karpova ◽  
Andrei A Lebedev ◽  
Petr D Shabanov

In the protocols of modern pharmacological studies of a self-stimulation reaction in rodents, stimulating electrodes are implanted as a rule unilaterally. The reinforcing properties of the left and right hypothalamus were suggested to be identical. The aim of the study was to clear up if the possibilities of the left and right hypothalamus to produce self-stimulation are similar or not. Methods. The study was carried out on adult male Wistar rats. The electrodes were implanted into the lateral hypothalamus bilaterally. The rats, in which an approach reaction was observed, learned self-stimulation in the Skinner box with stimulation of the left or right hypothalamus as a reinforcing agent descending thresholds of stimulation up to minimal one. Results. Self-stimulation of the left hypothalamus gave an approach reaction in the majority of rats (81.8%), self-stimulation reaction was developed in 72.7% of rats. Only 46.2% rats reacted on stimulation of the right hypothalamus, self-stimulation reaction was developed in 30.8% of rats. The thresholds of positive and negative reactions registered after electrical stimulation of both sides of hypothalamus were significantly differed (H(3, N = 31) = 14,92; p = 0,002). And these changes were not connected with lateralization but with sign of reaction: in general the thresholds of approach reaction were higher than thresholds of avoidance. Conclusion. In the paper, the fact of different possibility of approach reaction and self-stimulation development as a result of electrical stimulation of the left and right hypothalamus in rats has been described. After stimulation of the left hypothalamus, a possibility to receive positive reaction and to form self-stimulation on its basis is higher than after stimulation of the right hypothalamus. (For citation: Efimov NS, Bessolova YN, Karpova IV, et al. Asymmetry of reinforcing properties of the lateral hypothalamus in the self-stimulation test. Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(2):37-41. doi: 10.17816/RCF16237-41).


1993 ◽  
Vol 264 (2) ◽  
pp. R355-R361 ◽  
Author(s):  
R. R. Schick ◽  
S. Samsami ◽  
J. P. Zimmermann ◽  
T. Eberl ◽  
C. Endres ◽  
...  

Galanin has previously been reported to elicit feeding in satiated animals when injected into the hypothalamic paraventricular nucleus. It is not known, however, 1) whether this action is due to activation of feeding signals or suppression of satiety signals or both or 2) whether other hypothalamic regions such as the lateral hypothalamus (LH) or the ventromedial hypothalamus (VMH) are involved in this action. The effects of galanin on food intake were therefore examined in satiated and in fasted rats both after intracerebroventricular injection (0.1, 1, and 10 micrograms/10 microliters) and after microinjection (1 and 5 micrograms/0.5 microliters) into the LH and VMH. Twenty minutes after intracerebroventricular injection, galanin significantly and dose dependently augmented food intake by up to sevenfold in freely feeding rats and by up to 79% in fasted animals. The galanin-induced augmentation of cumulative food intake up to 2 h after injection was due to the initial increase in food consumption during the 0 to 20-min interval. This suggests that galanin acts by activation of feeding behavior and not by suppression of satiety signals in these fasted animals, in which satiety signals are presumably not initially operative. Twenty minutes after intrahypothalamic injections into both the LH and VMH, galanin (5 micrograms) significantly increased food consumption, fivefold in freely feeding rats and 30-35% in fasted rats. Thus stimulation of feeding by centrally injected galanin also involves loci within the LH and VMH.


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