Unilateral Olfactory Bulbectomy Research Articles

Monoclonal antibodies to the rat olfactory sustentacular cell

Immunization of BALB/c mice with rat olfactory epithelium permitted the production of a number of monoclonal antibodies directed towards cell types within the tissue. One of these antibodies, designated SUS-1, reacts specifically with cells located at the luminal surface of the olfactory neuroepithelium which possess a characteristic wine-glass body and a basal process which projects to the basement membrane. Thus these cells have the topographical and morphological properties of olfactory sustentacular cells. The SUS-1-positive cells are not stained by an antibody to the olfactory marker protein and neither does the SUS-1 antibody react with mature olfactory neurons in double labeling experiments. Upon unilateral olfactory bulbectomy there is a marked reduction in olfactory marker protein positive cells while there is no apparent diminution in the labeling of SUS-1 cells. These data show conclusively that the mature olfactory neurons and the SUS-1-positive cells are distinct from one another. SUS-1 staining is absent in all tissues examined except the olfactory epithelium. However, small discrete groups of cells in the lamina propria mucosae (often referred to as the submucosa) do stain in addition to the luminal sustentacular cell layer. The possibility is considered that the mature sustentacular cells may be related to these latter cells.

Rapid fiber reorganization after early olfactory tract section and bulbectomy in the hamster

AbstractDetails of neuronal reorganization were investigated in golden hamster pups 10 days after neonatal olfactory lesions. Pups sustained unilateral olfactory tract section (ULOT) or unilateral olfactory bulbectomy (UOB) on postnatal day 5 (P5) and were then behaviorally tested through P15. UOBs were sacrificed after P15 to assess the extent of lesions. ULOTs were processed with degeneration techniques to demonstrate the terminal distribution of bulb fibers whose path had been either deflected or severed by the early tract section.Ten days after complete tract section, extensive sprouting of bulb fibers had occurred rostral to the cut in olfactory as well as adjacent nonolfactory (e.g., neocortical) regions. The pattern of rostral sprouting was similar to, and in some cases exceeded, that described in adults subjected to neonatal tract sections (Devor, 76b). Fibers grew caudally past the cut following aberrant paths to reinnervate limited regions of the olfactory tubercle and less frequently, the piriform cortex. Unlike the continuous band of terminals soon in the caudal field of adults given neonatal tract sections, at this early stage of regrowth, fibers were organized in small discontinuous fascicles that tended to cluster at the islands of Calleja of the tubercle. Although these fibers innervated a relatively restricted region in comparison with normal innervation, their connections were apparently functional, as measured by a thermotaxis behavioral assay for the effects of UOB. The ther‐motaxis behavior of most pups showing tubercle reinnervation returned to normal, while the behavior of pups without tubercle reinnervation remained similar to UOBs (Small and Leonard, ′82). Excessive rostral sprouting and invasion of neocortex were seen in all tract‐sectioned pups and were, therefore, apparently not sufficient to sustain normal behavior on this assay.Regrowth of sensory olfactory fibers and extensive formation of glo‐meruli in the anterior olfactory nucleus and, occasionally, in prefrontal neocortex were found following olfactory bulbectomy. There was no correlation between the extent of glomerulization and the behavioral performance, however.The olfactory system provides an appropriate system for investigating the parameters governing age‐dependent axonal sprouting and functional recovery following early brain damage.

Early recovery of function after olfactory tract section correlated with reinnervation of olfactory tubercle.

Behavioral recovery and cortical reinnervation after early olfactory tract section were assessed in the infant golden hamster (Mesocricetus auratus). Hamster pups show strong thermotaxis at birth which declines abruptly after postnatal day (P) 8 in normal pups. Unilateral olfactory bulbectomy on P5 causes persistent thermotaxis through the second postnatal week. In this study, the bulb's output pathway, the lateral olfactory tract, was unilaterally severed on P5 and pup thermotaxis was tested through P15. Complete tract section, like bulbectomy, prolonged thermal responding beyond P8. In contrast to bulbectomy, however, some tract-sectioned pups showed recovery before P15 while others continued to show persistent thermotaxis throughout testing. The olfactory bulb projection was examined 10 days after tract section in order to determine whether recovery and persistent thermotaxis were associated with different patterns of cortical innervation. Eleven pups with complete transections showed recovery during the second week. In 10 of these pups, olfactory bulb fibers had penetrated the damaged region after surgery to reinnervate the olfactory tubercle. Three of these pups also exhibited some reinnervation of piriform cortex. The lesions of pups showing persistent thermotaxis were more severe, extending bilaterally or into deep cortical layers, and olfactory fibers had failed to reinnervate caudal terminal fields. All pups with olfactory tract sections showed extensive sprouting rostral to the cut, regardless of their behavioral profile. In no case had postlesion growth innervated the entorhinal or amygdaloid areas. Inhibition of thermotaxis was associated with reinnervation of the olfactory tubercle rather than more rostral, lateral or caudal olfactory cortex. We conclude that regrowth of olfactory tract fibers caudal to early transection is rapid and has functional consequences for early behavioral development.

Influence of unilateral olfactory bulbectomy on opiate and other binding sites in the contralateral bulb

The neurochemical consequences of unilateral olfactory bulbectomy (UBX) in mice were determined in the remaining olfactory bulb at various times after surgery. The most significant finding was a progressive decline in opiate ligand (dihydromorphine) and naloxone) binding that appeared within 11 days after surgery and persisted throughout the study. Statistically significant declines in spiroperidol (-67%), clonidine (-48%) and muscimol (-16%) binding were also observed 90 days after surgery. At 180 days postsurgery we observed a 20% increase in diazepam binding. No effect of UBX on dihydroalprenolol, quinucludinylbenzilate or serotonin ligand binding was observed. Bulbectomy resulted in a moderate decrease (-28%) in DOPA decarboxylase activity 14 days after surgery, which returned to normal by 30 days. Glutamic acid decarboxylase activity decreased by 37% 7 days after UBX, returned to normal by 14 days after surgery and then increased by 25% 90 days after UBX. Unilateral bulbectomy had no effect on cholineacetyltransferase activity in the remaining bulb. Thus, following a unilateral procedure, one bulb cannot necessarily serve as a valid control for the other. Possible explanations for the neurochemical changes observed are discussed.

Effects of olfactory bulb removal and flank shock on copulation in male rats

Sexually experienced male rats received bilateral olfactory bulbectomy (BOB, N=9), unilateral olfactory bulbectomy (UOB, N=7) or a sham operation (Sham, N=8). Copulation was severely disrupted in BOB males, whereas only minimal effects on copulation were observed in UOB males. Penile reflexes were not affected by either operation. Intermittent flank shock stimulated copulation in 5/6 BOB males. The BOB males that ejaculated had longer intromission latencies and longer postejaculatory intromission intervals than did Sham males receiving a similar schedule of shocks. Even so, all BOB males that ejaculated with flank shock also resumed copulation and ejaculated a second time without further shocks. Three BOB males that ejaculated with flank shock were tested the following week without shock, and none of these males copulated. These results strengthen previous conclusions that the olfactory bulbs are critical for the initiation and maintenance of sexual arousal in male rats.

Changes in electroencephalogram of the rat following olfactory bulbectomy.

The changes in electrical activities following olfactory bulbectomy were investigated in rats with chronically implanted electrodes, in comparison with those induced by septal lesions. Electroencephalogram (EEG) of the amygdala changed to low voltage fast waves immediately after bilateral olfactory bulbectomy, while EEG of the neocortex gradually showed an arousal pattern consisted of low voltage fast waves, and hippocampal theta waves were markedly synchronized during the period of a week or so after bulbectomy accompanied with the appearance of characteristic hyperemotionality. No change was observed in EEG of the septum, hypothalamus or the midbrain reticular formation. Following unilateral olfactory bulbectomy, no behavioral changes occurred, but EEG of the ipsilateral amygdala showed low voltage fast activity without causing any EEG changes in other brain structures. Bilateral septal lesions immediately caused hyperreactivity in rats which gradually disappeared during the course of a week or two after the surgery. The hippocampal theta activity completely disappeared and EEG turned to low voltage fast waves immediately after septal lesions, but no significant EEG change was observed in the amygdala or the neocortex. This change in hippocampal EEG continued for a long time even after hyperreactivity disappeared.

Collateral sprouting in central mesolimbic dopamine neurons: Biochemical and immunocytochemical evidence of changes in the activity and distribution of tyrosine hydroxylase in terminal fields and in cell bodies of A10 neurons

The olfactory tubercle of adult rats was examined for the development of collateral sprouts from intrinsic dopaminergic axons following unilateral olfactory bulbectomy. In the ipsilateral tubercle tyrosine hydroxylase (TH) activity began to increase by 10–14 days following the lesion, gradually reaching a maximum of 125% of control ( P < 0.005) by 21 days where it remained permanently elevated. The rise of TH activity in the tubercle reflected changes of the dopaminergic innervation, since dopamine-β-hydroxylase (DBH) activity was unchanged, and lesions of the dorsal noradrenergic bundle reduced DBH but not TH activity in the tubercle. By immunocytochemical staining the elevation of TH reflected an increased number and altered distribution of TH-containing processes within the olfactory tubercle. By 30 days the uptake of [ 3H]dopamine into synaptosomes of the olfactory tubercle was also increased to 140% of control ( P < 0.05). In the dopaminergic cell bodies of the ipsilateral A10 group (which innervate the tubercle) TH activity was transiently elevated to 121% ( P < 0.05) by 4 days, returning to control levels by 10 days. Histologically no change in activity was detected. The results indicate that mesolimbic dopaminergic neurons of A10 which innervate the olfactory tubercle will sprout in response to removal of a major non-dopaminergic input, that the new innervation is sustained, and that during collateral sprouting there is a transient elevation of TH activity in the uninjured cell bodies which precedes the period of axonal growth. The findings suggest that (a) the increase of TH activity in the A10 cell bodies during collateral sprouting may be a reflection of an increase in the amount of enzyme protein required for transport into the enlarging terminal fields, (b) that as in development sprouts are in place before they reach biochemical maturity, (c) the biochemical mechanisms underlying collateral sprouting of uninjured neurons are not necessarily the same as those associated with regenerative sprouting in response to axonal injury, and (d) the development and the acquisition of biochemical maturation of collateral sprouts in the CNS involves complex two-way signalling between terminal field and cell bodies. The development of collateral sprouts of dopaminergic neurons may be the cellular substrate of the development of behavioral hyperactivity and aggression produced by bilateral olfactory bulbectomy in rat.

Maturational loss of thermotaxis prevented by olfactory lesions in golden hamster pups (Mesocricetus auratus).

Five-day-old golden hamster pups were tested preoperatively on a thermal gradient, subjected to bilateral or unilateral olfactory bulbectomy or control dorsal cortical removal, and then tested on Days 6-15. Locomotion and rectal or belly temperature were monitored throughout the 2-min test. Control pups became quiescent in the hot end of the gradient on Days 5-7 but after Day 8 chose cooler regions and increased their activity. Both unilaterally and bilaterally bulbectomized pups spent more time in the heat throughout testing. They were also less active and allowed their temperature to rise more rapidly than controls. Percentage of time in the heat was elevated in all bulbectomized pups, although some retained the ability to make an olfactory discrimination. Enhanced thermal behavior is apparently not due to anosmia per se. Altered thermal perception or responsitivity may result from loss of "nonspecific" olfactory projections that normally would mature at the beginning of the second week.

Olfactory stimulation and olfactory bulb removal: Effects on territorial aggression in male Syrian golden hamsters

The Syrian golden hamster exhibits territorial aggression in a laboratory setting, attacking much more when in the home cage than in the cage of another hamster. In expt. 1 it was found that female hamster vaginal discharge (FHVD) greatly inhibits the territorial aggression of males. In expt. 2 it was found that hamster territorial aggression is almost completely eliminated by bilateral olfactory bulbectomy but is unaffected by unilateral olfactory bulbectomy. However, bilateral olfactory bulbectomized (BOB) hamsters fought back normally if attacked first. Blinding increased the territorial aggression of male hamsters. In expt. 3 a peripheral means of impairing olfaction was used. The results suggest that it is the olfactory impairment, rather than the loss of some hypothetical non-sensory functions of the olfactory bulbs, that causes the elimination of territorial aggression after olfactory bulbectomy. Because of the extensive secondary and tertiary olfactory projections to the limbic forebrain and hypothalamus, and because most laboratory mammals are macro-osmatic, the nature and degree of olfactory control should be an important consideration in studies on the neural basis of social behavior.

The effect of peripheral olfactory blockade on the social behavior of the male golden hamster

Bilateral olfactory bulbectomy eliminates mating and attenuates intermale investigatory and aggressive behavior in male golden hamsters (Mesocricetus auratus). Two reversible methods of peripheral olfactory blockage were found to mimic these effects. They were (1) unilateral olfactory bulbectomy combined with contralateral nostril occlusion and (2) bilateral reversible destruction of the olfactory epithelium by zinc sulfate infusion. These results indicate that a primary sensory deficit is sufficient to explain the effects of bulbectomy on social behavior and that incidental disruption of central nervous system tissue need not be invoked.