Olfactory Bulbectomies Research Articles

Ablation of olfactory bulb glutamatergic neurons induces depressive-like behaviors and sleep disturbances in mice.

Major depression is a serious, but common, psychological disorder, which consists of a long-lasting depressive mood, feelings of helplessness, anhedonia, and sleep disturbances. It has been reported that rats with bilateral olfactory bulbectomies (OBXs) exhibit depressive-like behaviors which indicates that the olfactory bulb (OB) plays an important role in the formation of depression. However, which type of OB neurons plays an important role in the formation of depression remains unclear. To determine the role of OB neuronal types in depression and related sleep-wake dysfunction. Firstly, we established and evaluated a conventional physical bilateral OBX depression model. Secondly, we used chemical methods to ablate OB neurons, while maintaining the original shape, and evaluated depressive-like behaviors. Thirdly, we utilized AAV-flex-taCasp3-TEVp and transgenetic mice to specifically ablate the OB GABAergic or glutamatergic neurons, then evaluated depressive-like behaviors. Compared with measured parameters in sham mice, mice with OBXs or ibotenic acid-induced OB lesions exhibited depressive-like behaviors and sleep disturbances, as demonstrated by results of depressive-like behavior tests and sleep recordings. Selective lesioning of OB glutamatergic neurons, but not GABAergic neurons induced depressive-like behaviors and increased rapid eye movement sleep during the light phase of the circadian cycle. These results indicate that OB glutamatergic neurons play a key role in olfactory-related depression and sleep disturbance.

Removal of the olfactory bulbs delays photic reentrainment of circadian activity rhythms and modifies the reproductive axis in male Octodon degus

The diurnal rodent, Octodon degus, exhibits robust sex differences in several circadian measures, including circadian period ( τ) and reentrainment rates to photic and nonphotic (social) zeitgebers. The neural substrates underlying such physiological differences remain unknown. In female degus, olfactory bulbectomies (BX) inhibit socially-facilitated reentrainment, but do not alter photic reentrainment, entrained measures, or τ in constant darkness (DD). This experiment investigated the effects of BX in male degus on (i) photic reentrainment rates of circadian rhythms following a 6-h phase advance of the light–dark (LD) cycle; (ii) photic entrainment; (iii) τ of free-running activity rhythms in DD; and (iv) body weight, paired testis weight, and the reproductive hormones, testosterone, androstenedione and follicle stimulating hormone (FSH). BX significantly delayed photic reentrainment rates. They did not, however, modify τ, the phase of activity onset or offset, amplitude or duration ( α) of the activity rhythm, mean daily locomotor activity levels, or body weight. FSH, testosterone and androstenedione were unaffected by BX, whereas paired testis weights were significantly greater in BX degus compared with shams. Thus, the olfactory bulbs influence photic reentrainment of circadian rhythms and modestly affect the reproductive axis in male degus. Our results suggest that the olfactory bulbs may be a neural source of observed sex differences in photic reentrainment in degus, and highlight interspecies variation in the olfactory bulbs' effects on entrained and free-running circadian rhythms and on reproduction.

Olfactory bulbectomy impedes social but not photic reentrainment of circadian rhythms in female Octodon degus.

Recent studies demonstrated that nonphotic (social) cues markedly accelerate reentrainment to large phase shifts of the light-dark (LD) cycles in female Octodon degus and that such changes are likely effected by chemosensory stimuli. This experiment investigated the effects of olfactory bulbectomies on (1) socially facilitated reentrainment rates of circadian rhythms following a 6-h phase advance of the LD cycle, (2) photic reentrainment rates of circadian rhythms following a 6-h advance of the LD cycle, (3) photic entrainment, and (4) the circadian period (tau) of activity rhythms in constant darkness (DD). olfactory bulbectomies (BX) blocked socially facilitated reentrainment rates but did not alter reentrainment rates of circadian rhythms to photic cues alone. In addition, BX lowered mean daily locomotor activity levels and decreased the amplitude of the activity rhythm in degus housed in entrained (LD 12:12) conditions but did not alter the phase of activity onset or offset, duration (alpha) of activity, or mean daily core body temperature. Bulbectomies also failed to modify tau of free-running activity rhythms. This experiment confirms that the olfactory bulbs and chemosensory cues are necessary for socially facilitated reentrainment. In contrast to their effects in nocturnal rodents, BX do not produce significant circadian photic changes in diurnal degus. This is the first experiment to determine that chemosensory stimuli modulate the circadian system in a diurnal rodent.

Gustatory and olfactory contributions to alcohol consumption in rats

To determine the relative contributions of taste and smell in the consumption of alcohol by rats, the present experiment tested normal rats ( n = 14) and rats with either gustatory cortex ablations ( n = 10), olfactory bulbectomies ( n = 11), or combination gustatory cortex and olfactory bulb ablations ( n = 12). Rats were tested under mild fluid deprivation using a two-bottle testing procedure. Thirteen concentrations of alcohol (0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, and 12%, v/v) were tested in ascending order. Results showed that at strong alcohol concentrations (7% through 11%) rats with combined gustatory cortex and olfactory bulb ablations consumed significantly more alcohol than normal control rats. Rats lacking gustatory cortex displayed a similar increased level of consumption with strong alcohol concentrations. It is suggested that the high level of consumption of strong alcohol concentrations by rats with central nervous system damage reflects an associative deficit rather than an alteration in taste or odor perception.

Alcohol aversion generalization in rats: specific disruption of taste and odor cues with gustatory neocortex or olfactory bulb ablations.

Rats with ablations of the gustatory neocortex (Experiment 1) and rats with olfactory bulb ablations (Experiment 2) were compared with normal rats for aversion generalization to both single taste solutions (sucrose, sodium chloride, quinine hydrochloride, hydrochloric acid) and compound taste solutions (pairs of the four single tastants) following alcohol aversion training. All rats acquired equal and strong alcohol aversions. Control rats showed consistent aversion generalization to both the sucrose + quinine and the sucrose + hydrochloric acid solutions; no significant generalization occurred to the single tastants except a weak generalization to sucrose in Experiment 2. Rats with gustatory neocortical ablations failed to show aversion generalization to any of the taste solutions. Rats with olfactory bulbectomies displayed the same aversion generalization functions as control rats but exhibited significantly faster extinction of the alcohol aversion than did the trained control rats. Results from the present experiments suggest that during alcohol aversion learning, rats lacking gustatory neocortex use odor cues (no taste generalization), whereas rats lacking olfactory bulbs utilize taste cues (normal taste generalization).

Reproductive effects of olfactory bulbectomy in the Syrian hamster.

The effects of olfactory bulbectomy on circulating gonadotropin, prolactin and testosterone levels and on the testicular and pituitary responses to shortening of day length were studied in Syrian hamsters. Adult animals maintained on a 14L:10D cycle were sham-operated or sustained bilateral radical olfactory bulbectomies by aspiration to remove the main and accessory olfactory bulbs and the adjacent regions of the anterior olfactory nucleus. They were then maintained either on the long photoperiod or housed on a 10L:14D cycle. Testicular length was measured at weekly intervals over a 5-mo period. Sham-operated controls exhibited the normal pattern of testicular regression and eventual recrudescence on the short photoperiod. Testicular regression was significantly reduced in bulbectomized animals. Many of these animals showed no regression; others exhibited a reduced degree and/or shortened duration of regression. Serum levels of follicle-stimulating hormone (FSH) were substantially elevated in bulbectomized males maintained in long days. Their serum levels of luteinizing hormone (LH), prolactin and testosterone remained within the range for shams on long photoperiod. In short days, the bulbectomized animals showed the normal, pronounced decline in circulating prolactin levels. Serum FSH and LH levels also showed substantial declines, but the FSH levels were not reduced below the range for controls in long days, and the decline in LH levels was not as great as that for controls in short days.(ABSTRACT TRUNCATED AT 250 WORDS)

Olfactory and vomeronasal system mediation of maternal recognition in the developing rat

Olfactory-mediated arousal and maternal recognition were evaluated in neonatal rat pups. Non-nutritionally deprived pups which underwent bilateral olfactory bulbectomies on day 5, failed to distinguish between the ventral and dorsal surfaces of a nursing rat and a heating pad. They showed virtually no arousal response to any of these surfaces. In contrast, pups with unilateral bulbectomies, and sham controls, graded their arousal response, and were maximally aroused by the mother's ventral surface. Following 24 h of maternal deprivation, bilaterally bulbectomized pups displayed a modest arousal response, directed primarily towards the dorsal surface. Pups with complete vomeronasal nerve sections displayed maximal arousal responses toward the dorsal surface. However, they were far more aroused than the bilaterally bulbectomized pups. Rat pups with incomplete vomeronasal lesions graded their response like controls, with maximal responsiveness directed toward the ventral surface. Shaving the dorsal surface markedly diminished the arousal response of bilaterally bulbectomized pups, but had only modest effects on sham and unilaterally bulbectomized controls. Thus, lesions that destroyed both the main and accessory's olfactory bulb systems severely impaired the pups' ability to effectively recognize a lactating female and markedly diminished maternally-induced arousal. Selective damage to the vomeronasal-accessory olfactory system appeared to disrupt discriminative capacity, but had little effect on the magnitude of the arousal response.

Filicidal behavior: Behavioral correlates and role of sensory systems

The administration of para-chloro-D,L-phenylalanine (PCPA) produces a high incidence of filicidal (pup-killing) behavior in female rodents. The present series of experiments determined the major behavioral, sensory, and temporal correlates of filicidal behavior in nulliparous adult Sprague-Dawley female rats. In Experiment 1, behavioral episodes involving the interaction of test pups and PCPA-induced filicidal females were videotaped, and subsequent analyses of behaviors related to locating, carrying, mauling, attacking, gnawing, and consuming the prey object were performed. Analysis indicated that the primary behavioral correlates in the PCPA animals included location, initiation of the attack (mauling), and killing of the pup (filicide). Only location was observed in control animals. Experiment 2 evaluated the effects of sensory impairments on location, mauling, and filicide. Sensory impairment occurred at 24 days of age for enucleation and 62 days of age for olfactory bulbectomies and/or auditory destruction. Animals were injected either at 110 or 130 days of age with PCPA for three consecutive days and tested for filicide for five additional days. Location of the test pup was not affected by sensory impairment. Mauling was reduced significantly in the enucleation/auditory destructed animals. Filicide was significantly lower in animals with visual/auditory destruction, and, compared to controls, was reduced in all sensory impaired groups.

Early VMH lesions in male and female rats: The role of hunger and olfactory bulbectomies in the initiation of the mouse killing

Early VMH lesions in male and female rats: The role of hunger and olfactory bulbectomies in the initiation of the mouse killing

Female sexual responses in male cats facilitated by olfactory bulbectomy and medial preoptic/anterior hypothalamic lesions.

Bilateral lesions of the medial preoptic/anterior hypothalamic area and olfactory bulbectomies were performed sequentially in sexually active male cats, with the order of operations balanced. Male sexual behavior was virtually eliminated by the combined operations in all cats. Increased levels of female proceptive behavior were seen following either type of lesion alone, and combined operations resulted in increased levels of receptivity. The results support the concept that there exists, within the brains of male animals, the neural basis for the display of female as well as male sexual responses and that certain brain operations may potentiate the display of female responses. However, it does not appear that the reduction of male behavior is necessarily coupled with an increase in female behavior since no correlation was seen between the degree of enhancement of female behavior and the decrement in male behavior.

Disruption of copulatory behavior of male rats by olfactory bulbectomy at two, but not ten, days of age

Male rats received bilateral olfactory bulbectomies or a sham operation at 2 days of age, 10 days of age, or in adulthood. Relative to sham-operated males, bulbectomy at 2 days of age or in adulthood reduced the proportion of males that copulated when tested as adults. In contrast, copulatory behavior was essentially normal in male rats bulbectomized at 10 days of age. The copulatory deficit in the Day-2 bulbectomized males was not a secondary effect of a testicular dysfunction because the age at preputial separation was normal and exogenous testosterone was ineffective in activating copulation in the noncopulating bulbectomized males. Neonatally bulbectomized males (both Day-2 and Day-10) showed a small, but significant, olfactory deficit when tested at 15 days of age, yet responded similarly to sham-operated males when tested in adulthood. Recovery of copulation after olfactory system damage appears to be dependent on the age of the animal at the time of the lesions. Furthermore, our results support previous suggestions that sparing of function is not a necessary consequence of the high plasticity of the developing nervous system.

Olfactory bulbectomy in infant rats: Survival, growth and ingestive behaviors

Growth and ingestive behaviors were measured for rats sustaining bilateral olfactory bulbectomies at 1 or 10 days of age. Tests designed to examine nipple-attachment capabilities were accomplished before weaning, and tests designed to examine drinking (e.g., water-deprivation), feeding (e.g., amphetamine-anorexia), and taste-related behaviors (e.g., quinine finickiness) were conducted from 35–150 days of age. Pups bulbectomized at 1 day of age displayed less severe nipple-attachment deficits than pups bulbectomized at 10 days of age; however, body weights of both bulbectomized groups were significantly below that of controls from the first day postsurgery through 150 days of age. Bulbectomized rats differed from controls on some drinking, feeding, and taste-related measures; deficits occurred most consistently on taste-related measures. The results are discussed in terms of neural and behavioral plasticity of developing animals sustaining neural damage.

Discrimination and generalization among reagent grade odorants by tiger salamanders (Ambystoma tigrinum)

Using an intense light as a negative reinforcer, two groups of tiger salamanders (Ambystoma tigrinum) were trained to respond to odorant-air mixtures of butyl acetate (8.9×10 −5M) or butyl alcohol (6.7×10 −5M). Then, they were given discrimination tests on which butyl acetate and butyl alcohol were presented successively, and generalization tests on which animals trained with butyl acetate were tested for generalization with propyl and amyl acetate, and the animals trained with butyl alcohol were tested with propyl and amyl alcohol. The salamanders then received either olfactory bulbectomies or sham surgeries. Post-surgical trials were given using the training odorant stimulus. Results indicated that salamanders discriminated between butyl acetate and butyl alcohol and that they generalized among acetates or alcohols chemically similar to their respective training odorant but not to filtered air. The immediate loss of conditioned response following bulbectomy but not sham surgery suggests that indeed olfactory cues were conditioned stimuli during the preceding phases of the experiment. Overall, these results are consistent with electrophysiological studies of olfaction in these animals.

Olfactory bulbectomy depresses ultrasound production and scent marking by female hamsters

Female hamsters were observed for rates of ultrasound production, vaginal marking and flank marking before and after bilateral olfactory bulbectomy, unilateral bulbectomy or sham operations. Unilaterally bulbectomized and sham-operated subjects maintained preoperative levels of each behavior. In contrast, females with bilateral olfactory bulbectomies showed consistent decreases in rates of vocalization and scent marking. These results emphasize the dependence on an intact olfactory system of several courtship or agonistic behaviors that affect hamster reproduction by functioning as noncontact communications. Together with the results of previous studies suggesting that lordosis by female hamsters is unaffected by olfactory bulbectomy, these data also suggest differences in the brain and sensory mechanisms that control distinct types of reproductive behavior.

Habituation of stimulus-elicited investigation in gerbils after olfactory bulbectomy

Normal gerbils habituate rapidly when presented with a novel object in the stimulus-elicited investigation paradigm. In this paradigm, gentled gerbils are given a series of one minute trials with a novel object in a small arena. They are then given a series of similar trials in which the odor of strange male gerbils is under one of five holes in the floor of the same arena. Gerbils with bilateral olfactory bulbectomies habituated more slowly to the object than normal gerbils or those anosmized peripherally by unilateral bulbectomy combined with stitching of the contralateral naris. In contrast, the two anosmic groups habituated at the same rate as normal gerbils when tested for investigation of five holes and odor although neither group of anosmic gerbils selectively localized the odor. In comparison to normal gerbils with no specific odor present, habituation was delayed for both experimental groups. In addition, both anosmic groups habituated normally on an activity score. Therefore, it was concluded that habituation can be affected differentially by the surgical conditions dependent on the task being measured. These data support the hypotheses (a) that the olfactory bulbs have a role in behaviors that are not dependent on olfactory information and (b) that habituation is not a single process mediated uniformly for all behaviors.

Pituitary/adrenal hormones do not influence bulbectomy-induced behavioural changes

The possible causal role of increased adrenal/function in olfactory bulbectomy-induced irritability and hyperactivity was investigated. Bilateral olfactory bulbectomies or sham operations were performed on sixty male Mongolian gerbils. Five days later daily injections of dexamethasone phosphate (which suppresses ACTH and, indirectly, cortisol), metyrapone (which inhibits production of cortisol and indirectly increases ACTH) or saline were begun and continued throughout the period of testing. Bulbectomized animals were more active in an open field apparatus, more aggressive in grouped and paired social interaction tests, and initiated more non-aggressive contacts in paired social interaction tests. Both dexamethasone and metyrapone led to increased activity in the open field but did not significantly affect any other measure. Neither dexamethasone nor metyrapone significantly decreased any of the behavioral changes resulting from bulbectomy. These results are taken as evidence that physiological levels of the hormones of the pituitary/adrenal axis are not essential for bulbectomy-induced behavioral changes in the male gerbil.

Mating in male Mongolian gerbils after olfactory bulbectomy

Adolescent male Mongolian gerbils received complete olfactory bulbectomies that were verified histologically. When mature, each lesioned gerbil mated and inseminated normal female gerbils. The loss of the sense of olfaction in the lesioned gerbils was demonstrated by 2 tests in which the animals did not investigate conspecific odors or seek food odors.

Blocked sexual receptivity in grouped female golden hamsters, the result of contact induced inhibition.

Female hamsters maintained in groups show normal estrous cyclicity, but a significant number fail to exhibit normal mating behavior (blocked lordosis). Three experiments examined the influence of exteroceptive stimuli on this block to female sexual receptivity. Two experiments tested the possibility that a pheromonal mechanism is responsible for the behavioral block. Forty-two singly caged hamsters received either olfactory bulbectomies or sham operations. The hamsters were then grouped. Anosmic and intact hamsters equally showed the blocked lordosis. Thirteen blocked hamsters received either bilateral olfactory bulbectomies or sham operations. None of the blocked hamsters returned to lordosis. These experiments provide strong evidence against an olfactory-mediated mechanism for the block to female receptivity. The third experiment examined the hypothesis that the block to sexual receptivity is mediated by contact behaviors. Using our standard group living cage, 46 × 30 × 25 cm, 6 hamsters had access to the entire cage or were confined by wire mesh partitions to cubicles, each one sixth of the total cage volume (23 × 10 × 25 cm). Twelve hamsters were placed in grouped conditions while 30 were placed in partitioned compartments. While one third of the grouped animals displayed blocked lordosis, none of the compartmentalized hamsters was blocked. When the compartmentalized hamsters were grouped, 27% failed to exhibit lordosis. Thus contact behaviors are involved in mediating the block in lordosis found when female hamsters are maintained under group living conditions.

Olfactory bulbectomy, peripheral anosmia, and mouse killing and eating by rats

Seventeen rats which had not killed a mouse in 6 wk sustained bilateral olfactory bulbectomies. Fifteen of these started to kill after surgery, and nine consistently killed on the same day the mouse was introduced. Twelve nonkillers sustained surgical ablation of the olfactory receptors. None of these killed after surgery. Of eight spontaneous killers which consistently killed on the day a mouse was introduced, four sustained receptor ablations, and three, bulbectomies. One remained an unoperated control. All killed as quickly and as consistently as before. Most bulbectomized rats employed an “emotional,” messy style of killing, and bulbectomy-facilitated killers ate less of their prey than did spontaneous killers. Deafferentation had no effect on killing or eating. This is interpreted as evidence for irritable aggression on the part of bulbectomized rats, and for a nonolfactory role of the olfactory bulbs.

Olfactory control of sexual behavior in the male and early-androgenized female hamster

Thirty-seven female hamsters, treated with either sesame oil or testosterone postnatally on days 2, 4, or 10 of life, and 25 male hamsters were given either olfactory bulbectomies or sham operations and tested for mounting behavior in adulthood. Extensive lesioning of the olfactory bulbs eliminated mounting in all subjects, suggesting that the mounting of early androgenized females is dependent upon the same sensory channels as the mounting of the males.