Recovery of olfactory function in thirteen-day-old rats after olfactory bulb transplantation but not after olfactory bulb ablation.

Previous studies have shown recovery of olfactory ability along with reconnectivity of olfactory nerve (ON) following both olfactory bulb (OB) lesions and OB transplants (TX) when performed in newborn rats. The purpose of the present study is to correlate functional recovery with patterns of anatomical reconnectivity in older, postnatal (PN) 13-day-old rats (a possible critical period for plasticity in the system). Reinnervation of olfactory areas was seen in all OB TX animals regardless of the extent of functional recovery. Eight of nineteen animals with OB TXs demonstrated some degree of behavioral recovery. No reinnervation or behavioral recovery of OB lesion animals was observed. At this age, behavioral recovery is dependent upon reconnectivity within the system and transplantation may be required to facilitate this process.

Olfactory bulb transplants establish afferent and efferent connections with host forebrain in rat.

We are using wheat germ agglutinin-conjugated horseradish peroxidase (WHRP) to study reconnectivity in the transplanted (TX) olfactory bulb (OB) in Sprague-Dawley rats. Tritium-labeled OBs from fetal rat donors of Embryonic Days 14-15 were immediately grafted into neonatal rats in the site from which the host OB had been removed. Following survival times of 7 weeks and longer, WHRP solution was injected into the TX OB, and subjects were perfused after 24 h. The WHRP transport is seen in fibers from the TX OB into layer I of the host olfactory peduncle (OP) and olfactory cortex (OC) and in cell bodies in layers II and III of the OP and OC, the lateral hypothalamus, and the contralateral anterior olfactory nucleus (AON). These findings reaffirm that the axons from a TX OB make connections with some appropriate areas of the host brain and also indicate that axons from cells in the target areas of the host brain, including contralateral AON, reinnervate the TX OB.

Recovery of olfactory behavior. I. Recovery after a complete olfactory bulb lesion correlates with patterns of olfactory nerve penetration.

The olfactory system is an excellent system in which to study issues related to potential functional recovery after a debilitating brain injury. The olfactory system is well-characterized, easily accessible and there are a vast number of studies available from a variety of perspectives. The experimental aim of this research is to examine the anatomical correlates associated with potential behavioral recovery in rats that receive complete olfactory bulb lesions as neonates or as adults. The results show that behavioral recovery occurs only when olfactory nerve penetration of the central nervous system is observed. Further, both olfactory nerve penetration and behavioral recovery are age-dependent phenomena. The olfactory nerve penetration only occurs when the olfactory bulb lesion is performed in neonates. Behavioral recovery of olfactory ability follows a linear trend and reaches near normal levels during the six weeks behavioral testing period. Histological analysis using an antibody for olfactory marker protein (an olfactory nerve-specific marker) reveals two potential candidates for the anatomical pathway responsible for behavioral recovery: olfactory nerve to orbital frontal cortex and olfactory nerve to olfactory peduncle. This report presents evidence that recovery of olfactory ability can occur in the absence of the olfactory bulb if the lesion is performed when the rat is still a neonate.

Recovery of olfactory behavior. II. Neonatal olfactory bulb transplants enhance the rate of behavioral recovery.

Previous experiments in this laboratory have shown that transplants of a fetal olfactory bulb into a neonatal rat are viable and that they establish connections with the olfactory peduncle and olfactory cortex. The focus of this experiment was to investigate the anatomical correlates of any behavioral recovery seen in rats that had one olfactory bulb removed along with an immediate transplant of a fetal olfactory bulb. Anatomical details, such as transplant organization and olfactory nerve repenetration patterns were analyzed using a variety of histological and immunohistochemical techniques. The rats in this experiment showed behavioral recovery of olfactory ability. The recovery rates observed in these animals were compared to two other groups of rats that this laboratory has shown to be behaviorally competent: normal rats and rats with neonatal ablations of the olfactory bulb but no transplant. Although the animals with transplants did not recover to completely normal levels of olfactory ability, they did start behavioral testing in a more behaviorally competent condition than rats with simple neonatal lesions. Anatomical analysis revealed that the transplanted olfactory bulb was heavily penetrated by incoming olfactory nerve fibers but olfactory nerve penetration was not limited to the transplanted olfactory bulb. The extra-bulbar host regions that were penetrated included the orbital frontal cortex and three olfaction-related areas; olfactory cortex, olfactory peduncle and the subependymal cell layer. The olfactory nerve penetration patterns observed beyond the transplant were essentially the same as those observed in rats with only neonatal lesions of the olfactory bulb. Thus, multiple pathways may have contributed to the recovery observed in the rats with olfactory bulb transplants.