Robert Coopersmith

NMDA receptor activation and early olfactory learning.

Norway rat pups have an enhanced olfactory bulb response to odors which they have learned to prefer early in life. When N-methyl-D-aspartate receptors are blocked pharmacologically before olfactory preference training, both the behavioral preference and the enhanced olfactory bulb response to the learned odor are suppressed. These results implicate the activation of these receptors in the kind of neural and behavioral plasticity that normally occurs during development.

Enhanced neural response by adult rats to odors experienced early in life

The enhanced olfactory bulb neural response to familiar odors by young rats persists into adulthood. Ninety-day-old rats who had received neonatal odor exposure had an enhanced uptake of [14C]2-deoxyglucose (2-DG) when exposed to the familiar odor. The odor-familiar rats did not have an increased respiration rate during the 2-DG test. A long-lasting change in neuronal response is consistent with the observation of behavioral effects of early odor experience persisting into adulthood.

Extracellular dopamine increases in the neonatal olfactory bulb during odor preference training.

Young rats learn to approach an odor that has been paired with tactile stimulation. This attraction is accompanied by changes in the metabolism and anatomy within the olfactory bulb glomerular layer. In this study, we examined the changes that occur in the olfactory bulb during early olfactory learning, rather than after such pairings have occurred. Specifically, we determined whether the pairing of an odor with tactile stimulation would produce a modified response by olfactory bulb glomerular-layer neurons. To monitor one large subgroup of these neurons during early learning, we used in vivo microdialysis to assess the activity of dopaminergic neurons in the olfactory bulb of postnatal day (PND) 3 rats during simultaneous presentation of odor and tactile stimulation, tactile stimulation alone, odor alone, or clean air alone. Clean air evokes no change in extracellular dopamine (DA), while both odor alone and stroking alone induce prolonged increases in DA peaking at about 200% of baseline. The combination of odor and tactile stimulation, which allows an olfactory preference to be formed, induces a prolonged increase in DA which peaks at about 400% of baseline. The level of the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) increases only in pups receiving both odor and tactile stimulation and peaks at about 200% of baseline. With the exception of the pups exposed to clean air, all groups show an increase in homovanillic acid (HVA) of between 150-200% following stimulation. The large and prolonged increase in DA may be linked to the longer term anatomical and physiological changes in the glomerular layer of the bulb that form as a consequence of early olfactory preference training.

Odor specificity of the enhanced neural response following early odor experience in rats

The enhanced neural response in the olfactory bulbs of rat pups following early olfactory experience is specific to the familiar odor. Pups were exposed daily to either peppermint or cyclohexanone odor for the first 18 postnatal days. On day 19, peppermint-familiar pups exposed to peppermint had significantly higher [14C]2-deoxyglucose (2-DG) uptake in a focal glomerular area compared with the response to peppermint by cyclohexanone-familiar pups. We also found that cyclohexanone-experienced pups had a subsequent enhanced response to cyclohexanone odor in glomerular areas medial and caudal to those responding to peppermint. None of the 2-DG uptake differences were attributable to respiration differences between the groups during any part of the odor test.

Glutathione levels in olfactory and non-olfactory neural structures of rats

Olfactory receptor neurons are a CNS entry point for a wide variety of airborne substances. Therefore, it is probable that detoxification mechanisms are present in these neurons to neutralize such agents. Glutathione (GSH) is an essential component of several detoxification schemes, and in this study we examined the distribution and levels of GSH in the olfactory epithelium, olfactory bulb, cortex, hippocampus and cerebellum in neonatal, weanling, adult and aged rats. We report that GSH is primarily localized to the olfactory receptor neurons and their oxons within the olfactory epithelium. It is also localized within the glomerular neuropil and granule cells of the olfactory bulb. Levels of GSH in the olfactory epithelium and hippocampus do not change as a function of age, although GSH levels decrease in several brain regions, including the olfactory bulb, cerebellum and cortex.

Development of olfactory bulb organization in precocial and altricial rodents

The structural organization of the olfactory bulbs of spiny mice, Norway rats and Mongolian gerbils was followed over the course of their development. The pups of all 3 species normally begin to approach the odor of their dams at a time when their olfactory bulbs are at a similar stage of development. The data suggest that there may be a common aspect of olfactory bulb development that underlies the onset of olfactory guided approach behavior in rodents.

Olfactory bulb responses after odor aversion learning by young rats

The increased olfactory bulb response by young rats to familiar odors was not observed in response to odors which have attained their familiarity in aversive situations. Odor experience associated with toxicosis induced a behavioral aversion to the odor which was not accompanied by the enhanced uptake of [14C]2-deoxyglucose (2-DG) that accompanies attractive familiar odors. A single odor exposure on day 17 was sufficient to induce a small increase in 2-DG uptake in specific glomerular areas. We hypothesize that a different neural substrate underlies familiarity associated with an aversive odor than that associated with an attractive odor.

Diurnal cycle of mother-young contact in Norway rats.

Mother rats maintained on a LD 12:12 photoperiod (lights on 0800 hrs) had longer contact bouts with their offspring during the day than during the night and maternal brain temperature peaked during the night. When the daily temperature cycle was suppressed by removal of adrenal and ovarian hormones, the daily maternal contact cycle was also suppressed. These data are consistent with a thermal model for the limitation of mother-young contact bout duration.

Olfactory bulb glycogen metabolism: noradrenergic modulation in the young rat

The olfactory bulb exhibits high glycogen phosphorylase activity, the rate-limiting enzyme in the mobilization of glycogen. The bulb also receives dense noradrenergic innervation and noradrenaline is known to stimulate glycogen breakdown. We determined the levels of glycogen in the bulb over the course of development and then determined the ability of noradrenaline to mobilize bulb glycogen. At birth, olfactory bulbs have very high levels of glycogen, with levels declining as the pups develop. Picomolar levels of noradrenaline mobilize glycogen in the bulb,. Initially, beta-adrenergic receptors mediate teh glycogenolysis and subsequently, the alpha-noradrenergic receptors in the bulb stimulate the breakdown of glycogen. Carnosine is involved in the repletion of bulb glycogen levels. The stimulation of glycogen breakdown by noradrenaline may play a role in allowing the increased activity that accompanies early olfactory stimulation.

Biochemical quantitation and histochemical localization of glucose-6-phosphate dehydrogenase activity in the olfactory system of adult and aged rats.

The activity of glucose-6-phosphate dehydrogenase, the rate-limiting enzyme of the hexose monophosphate shunt, was examined in olfactory epithelium, respiratory epithelium, olfactory bulb, and occipital cortex in Fisher 344 rats aged 4 and 24 months. Marked differences in this enzyme were found in olfactory compared to nonolfactory tissues. Olfactory epithelium and olfactory bulb have much greater glucose-6-phosphate dehydrogenase activity than respiratory epithelium and occipital cortex at both ages. Glucose-6-phosphate dehydrogenase remains fairly constant between adulthood and senescence in respiratory epithelium and occipital cortex. However, glucose-6-phosphate dehydrogenase activity decreases during the same time in both of the olfactory tissues examined. Previous studies of changes in this enzyme with aging have shown increases in enzyme activity in some brain regions, but never the decreases that we describe in olfactory tissues. Glucose-6-phosphate dehydrogenase histochemistry revealed intense staining of both the apical layer of olfactory epithelium and of Bowmans glands along with their ducts. Histochemistry of the olfactory bulb showed strongest staining in the nerve and glomerular layers of the bulb. The functional implications of these findings are discussed.