Faculty Bibliography

In Experiment 1, infant rats were implanted with a stimulating electrode in the medial forebrain bundle/lateral hypothalamus (MFB/LH) on postnatal day 12 (PN12). Four to 6 hours later, the pups underwent associative olfactory conditioning, with half of the pups trained with 30 temporal pairings of odor (5 s) and MFB/LH stimulation (200 Hz, 300 ms), and the other half trained with random presentations of odor and MFB/LH stimulation. On PN13, pups were tested for: (1) behavioral preference for the conditioned odor; (2) focal glomerular layer 2-DG uptake to the odor; or (3) mitral/tufted cell single-unit response pattern to the odor. Odor-MFB/LH pairings produced a relative behavioral preference, enhanced focal 2-DG uptake and a modified mitral/tufted cell response pattern to the conditioned odor. Random training resulted in none of these changes. In Experiment 2, PN12 pups were anesthetized with urethane and single-unit responses of mitral/tufted cells to MFB/LH stimulation were examined. MFB/LH stimulation produced a brief suppression of mitral/tufted cell activity followed either by a prolonged excitation (18/30 cells; 8-10 s duration) or a prolonged suppression (12/30 cells; 10-30 s). These results suggest that pairing olfactory nerve input with MFB/LH stimulation modifies subsequent behavioral and physiological responses to olfactory nerve input alone. Furthermore, the prolonged olfactory bulb response to MFB/LH stimulation may be critical in this modification

Rat pups acquire an attraction for maternal odors, which can vary with maternal diet. In the two experiments reported here, maternal diet was modified and both pup behavioral responses and pup olfactory bulb neural responses [( 14C]2-DG uptake) to maternal odors were examined. In experiment 1, pups were reared from birth to postnatal day 19 with either a dam fed normal rat chow or a dam fed a sucrose-based diet which suppressed her normal maternal odor. In experiment 2, pups were raised from birth to postnatal day 19 with either a dam fed the sucrose-based diet adulterated with peppermint, or the non-scented sucrose-based diet. Pups selectively expressed both a behavioral attraction and an enhanced olfactory bulb neural response to odors that they experienced in the nest

Acquisition of behavioral conditioned responding and learned odor preferences during olfactory classical conditioning in rat pups requires forward or simultaneous pairings of the conditioned stimulus (CS) and the unconditioned stimulus (US). Other temporal relationships between the CS and US do not usually result in learning. The present study examined the influence of this CS-US relationship upon the neural olfactory bulb modifications that are acquired during early classical conditioning. Wistar rat pups were trained from Postnatal Days (PN) 1-18 with either forward (odor overlapping temporally with reinforcing stroking) or backward (stroking followed by odor) CS-US pairings. On PN 19, pups received either a behavioral odor preference test to the odor CS or an injection of (14)C 2-DG and exposure to the odor CS, or olfactory bulb single unit responses were recorded in response to exposure to the odor CS. Only pups that received forward presentations of the CS and US exhibited both a preference for the CS and modified olfactory bulb neural responses to the CS. These results, then, suggest that the modified olfactory bulb neural responses acquired during classical conditioning are guided by the same temporal constraints as those which govern the acquisition of behavioral conditioned responses

Postnatal olfactory learning produces both a conditioned behavioral response and a modified olfactory bulb neural response to the learned odor. The present report describes the role of norepinephrine (NE) on both of these learned responses in neonatal rat pups. Pups received olfactory classical conditioning training from postnatal days (PN) 1-18. Training consisted of 18 trials with an intertrial interval of 24 hr. For the experimental group, a trial consisted of a pairing of unconditioned stimulus (UCS, stroking/tactile stimulation) and the conditioned stimulus (CS, odor). Control groups received either only the CS (Odor only) or only the UCS (Stroke only). Within each training condition, pups were injected with either the NE beta-receptor agonist isoproterenol (1, 20, or 4 mg/kg), the NE beta-receptor antagonist propranolol (10, 20, 40 mg/kg), or saline 30 min prior to training. On day 20, pups received one of the following tests: (1) behavioral conditioned responding, (2) injection with 14C-2-deoxyglucose (2-DG) and exposed to the CS odor, or (3) tested for olfactory bulb mitral/tufted cell single-unit responses to the CS odor. The results indicated that training with either: (1) Odor-Stroke-Saline, (2) Odor-Stroke-Isoproterenol-Propranolol, or (3) Odor only-Isoproterenol (2 mg/kg) was sufficient to produce a learned behavioral odor preference, enhanced uptake of 14C-2-DG in the odor-specific foci within the bulb, and a modified output signal from the bulb as measured by single-cell recordings of mitral/tufted cells. Moreover, propranolol injected prior to Odor-Stroke training blocked the acquisition of both the learned behavior and olfactory bulb responses. Thus, NE is sufficient and may be necessary for the acquisition of both learned olfactory behavior and olfactory bulb responses

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

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

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