Faculty Bibliography

Noradrenergic centrifugal inputs to the rat olfactory bulb mainly terminate on granule cells, which are inhibitory interneurons. In the mature bulb, norepinephrine suppresses granule cell activity, thus increasing the excitability of the primary output neurons of the bulb. However, since the majority of granule cells develop postnatally, the effectiveness of noradrenergic inputs to the bulb during development is unclear. The present report describes the postnatal development of noradrenergic modulation of olfactory bulb function by examining the effects of noradrenergic beta-receptor agonists and antagonists on paired-pulse inhibition at the granule cell/mitral cell reciprocal synapse. The results demonstrate that noradrenergic modulation of olfactory bulb excitability emerges during the first postnatal week in the rat. These results suggest that noradrenergic centrifugal control of olfactory bulb activity appears early during postnatal development, and thus is capable of playing an important role in pup responses to olfactory cues early in life

1. Neonatal rat pups were classically conditioned to an odor stimulus from postnatal day 1 (PN1) to PN18. Tactile stimulation (stroking) was used as the unconditioned stimulus. On PN19, mitral/tufted cell single-unit responses to the conditioned odor were examined in both conditioned and control pups. Recordings were made from mitral/tufted cells in two regions of the olfactory bulb: 1) an area typically associated with focal [14C]2-deoxyglucose (2-DG) uptake in response to the conditioned odor and 2) an area distant from focal 2-DG uptake to the conditioned odor. Animals were anesthetized with urethane and were naturally respiring during the single-unit recording procedure. 2. Changes in mitral/tufted cell firing rate in response to odors in both bulbar regions and all training groups were classified as either excitatory, suppressive, or no response. This response classification was used to compare response patterns to the conditioned odor between bulbar regions and training groups. 3. Classical conditioning selectively modified the response patterns of mitral/tufted cells to the conditioned odor when those cells were associated with regions of focal 2-DG uptake for that odor. Mitral/tufted cells demonstrated significantly more suppressive and fewer excitatory responses to the conditioned odor than cells in control pups. Response patterns to a novel odor were not similarly modified. 4. Response patterns of mitral/tufted cells distant from the focal region of 2-DG uptake to the conditioned odor were not modified by conditioning compared with control pups. 5. The difference in response pattern between cells in the 2-DG focus and cells distant to the 2-DG focus was apparent within 500 ms of the stimulus onset. Given the respiratory rate of these pups (2 Hz), these data suggest that the modified response pattern occurred on the first inhalation of the learned odor. 6. These data demonstrate that both spatial and temporal patterns of olfactory bulb output neuron activity are used in the coding of olfactory information in the bulb. Furthermore, these spatial/temporal response patterns can be modified by early learning

Previous work indicated that physical stimulation, such as that which mimics the stimulation pups receive from the dam, reduces pup body temperature. The present paper reports that the body and brain temperature of 5-day-old pups covaried under steady-state thermal conditions, cold exposure, and warmth exposure (Expt. 1) suggesting that body thermoregulatory mechanisms may also regulate brain temperature. Indeed, physically stimulating pups decreased brain temperature in the neocortex (Expt. 2) and the olfactory bulb (Expt. 3). The mechanism for this brain temperature decrease appears to be an increase in ventilatory heat exchange, the same mechanism responsible for the decrease in body temperature. Pups increased respiration during stimulation, thereby increasing air flow to the lungs where convective and evaporative heat exchange occurred. Indeed, stimulating pups in a high-humidity environment blocked the decrease in brain temperature (Expt. 4). The ability of physical stimulation to decrease brain temperature appears to be limited to neonatal pups, as 10-, 15-, and 20-day-old pups did not exhibit a brain temperature decrease in response to stimulation (Expt. 5)

Following olfactory classical conditioning, infant rats exhibit a preference for the conditioned odor and exhibit enhanced uptake of focal 14C 2-deoxyglucose (2-DG) within the olfactory bulb. The present experiments assessed the role of respiration on the expression of the enhanced 2-DG uptake response. Pups were conditioned from postnatal day (PN) 1-18 with an olfactory stimulus paired with a reinforcing tactile stimulus which mimics maternal contact (Odor-Stroke). Control pups received odor only or tactile stimulation only. On PN 19, pups received 1 of 3 tests: 1) a two-odor choice test, 2) an odor/2-DG test with normal respiration allowed, or 3) an odor/2-DG test with respiration experimentally controlled. The results indicated that: 1) Odor-Stroke pups learned the conditioned odor preference, 2) Odor-Stroke, normally respiring pups exhibited enhanced olfactory bulb 2-DG uptake when compared to control pups. No difference in respiration rate was detected between groups in normally respiring pups. 3) Odor Stroke pups whose breathing was experimentally controlled exhibited enhanced olfactory bulb 2-DG uptake when compared to control pups with an identical number of respirations. Together, these results demonstrate that modified respiration during testing is not required for the expression of a modified olfactory bulb response to learned attractive odors. Therefore, the data suggest that the olfactory system itself is modified by early learning

Neonatal rats learn to approach odors associated with stimulation normally provided by their mother. The present report describes changes in olfactory bulb single-unit activity following olfactory learning in young rats. Rat pups were exposed from postnatal day 1 to 18 to either (1) peppermint-scented air while receiving tactile stimulation (Pepp-Stroked), (2) peppermint-scented air with no tactile stimulation (Pepp-Only), (3) clean air and tactile stimulation (Stroked-Only), or (4) clean air and no tactile stimulation (Naive). On day 19, single-unit activity was recorded from mitral/tufted cells in urethane-anesthetized, freely breathing pups in response to either peppermint or a novel orange odor. Mitral/tufted cell response patterns to peppermint were significantly altered in Pepp-Stroked animals compared to control pups. Peppermint exposure alone, not associated with tactile stimulation (Pepp-Only), did not affect subsequent single-cell response patterns to that odor. In addition, the modification of response patterns was specific to peppermint and was not associated with a change in respiration rate. Furthermore, Pepp-Stroked pups had a relative behavioral preference for peppermint on day 19 compared to control pups. These results demonstrate that postnatal olfactory learning selectively modifies the subsequent response patterns of olfactory bulb output cells to the attractive odor. Furthermore, these results indicate that the initial coding of an odor's attractive value occurs within the olfactory bulb

Lateral inhibitory circuits are found throughout the nervous system. While the neuroanatomical basis for lateral inhibitory interactions exists in the olfactory bulb of Norway rats, there has been no direct demonstration of lateral inhibition in the responses of olfactory bulb output neurons to odor stimulation. In this report we recorded the extracellular activity of a large number of sequentially recorded mitral/tufted cells in response to odor stimuli at two different concentrations, as well as the inter-cell distance between these cells. The probability of recording two cells with excitatory responses to the same odor was then determined for inter-cell distances up to 500 microns. For cells stimulated with high concentration odors, the probability of two cells 100-200 microns apart both being excited by the same odor was significantly lower than that predicted if all cells responded independently. Cells separated by greater or shorter inter-cell distances did not differ from the predicted value. Responses to the low odor concentration were not dependent on inter-cell distance. These results demonstrate that lateral synaptic interactions within the olfactory bulb influence output cell responses to odor stimulation

Olfactory bulb responses to paired-pulse stimulation of the lateral olfactory tract were examined in urethane-anesthetized rats, aged 5 days to adult. Brief inter-pulse intervals resulted in a depression of test responses at all ages. The magnitude of this depression decreased dramatically between postnatal days 19 and 20 to approach adult levels. Longer inter-pulse intervals resulted in a facilitation of test response amplitude in adult animals. This facilitation was evident at adult levels by postnatal day 10. These results suggest that both inhibitory and facilitatory synaptic mechanisms appear early in the course of rat olfactory bulb development. Furthermore, presumed granule cell-mediated inhibition is present at unusually high levels in the developing bulb, decreasing sharply between days 19 and 20

The functional development of inhibition in the rat olfactory bulb was examined in the present study. Inhibition of presumed mitral cell spontaneous activity following stimulation of the lateral olfactory tract was present by postnatal day 5, the youngest age tested. The duration of this inhibition was greatest in young animals, decreasing after postnatal day 15. Possible mechanisms of this enhanced inhibition in neonates were discussed