Faculty Bibliography

Exposure to odorants results in a rapid (<10 s) reduction in odor-evoked activity in the rat piriform cortex despite relatively maintained afferent input from olfactory bulb mitral cells. To further understand this form of cortical plasticity, a detailed analysis of its odor specificity was performed. Habituation of odor responses in anterior piriform cortex single units was examined in anesthetized, freely breathing rats. The magnitude of single-unit responses of layer II/III neurons to 2-s odor pulses were examined before and after a 50-s habituating stimulus of either the same or different odor. The results demonstrated that odor habituation was odor specific, with no significant cross-habituation between either markedly different single odors or between odors within a series of straight chain alkanes. Furthermore, habituation to binary 1:1 mixtures produced minimal cross-habituation to the components of that mixture. These latter results may suggest synthetic odor processing in the olfactory system, with novel odor mixtures processed as unique stimuli. Potential mechanisms of odor habituation in the piriform cortex must be able to account for the high degree of specificity of this effect

Respiratory airflow outside the external nares of the rat was mapped by monitoring temperature fluctuations with a thermistor and simultaneous piezoelectric monitoring of respiration-associated chestwall movement. The results demonstrated that both exhalation and inhalation airflow were directed laterally. Relatively little air exchange occurred anterior to the nares. These results suggest that the two nares of the rat take independent, bilateral samples of the odor environment. Combined with recent descriptions of laterally specific, spatial receptive fields in piriform cortical neurons, an hypothesis is outlined describing a mechanism of odor orientation in the rat involving comparisons of timing or intensity of bilateral odor stimulation

PURPOSE: When prenatal ultrasound reveals urinary tract dilatation, fetal reflux is suspected. Postnatal voiding cystourethrography confirms the diagnosis. The origin of reflux nephropathy is controversial, and the roles of urinary tract infection and pressure effects of sterile reflux on the developing kidneys are debatable. We evaluate the relationship between sterile reflux and renal scarring. MATERIALS AND METHODS: We reviewed the records of 100 infants and children seen during a 15-year period in whom fetal reflux had been diagnosed, including 81 with bilateral and 19 with unilateral vesicoureteral reflux. In 12 of the 19 patients voiding cystourethrography revealed unilateral grade IV or V reflux, and they comprise the study group. Split renal function was measured in all 12 patients by radionuclide renal scan shortly after birth and before urinary tract infection developed. RESULTS: Individual renal function was 0 to 40% in all refluxing renal units. Split renal function was less than 10% in 3 kidneys, 10 to 30% in 5 and 30 to 40% in 4. There were 2 nonfunctioning kidneys. In the remaining 10 kidneys isotope distribution on the nuclear scan indicated decreased renal length and mass. Subsequently 7 patients had breakthrough urinary tract infections while on antibiotic chemoprophylaxis. Nephrectomy, and nephroureterectomy and ureteral reimplantation with or without tapering were performed in 3 and 9 refluxing ureters, respectively. Pathological examination of the 3 nephrectomy specimens revealed severe renal dysplasia consisting of persistent primitive ducts and nests of metaplastic cartilage. CONCLUSIONS: Our study supports the notion that renal impairment associated with severe fetal reflux is present at birth, and it is likely due to congenital dysplasia.

Responses of anterior piriform cortex layer II/III neurons to both odors and electrical stimulation of the lateral olfactory tract (LOT) were measured with intracellular recordings in urethan-anesthetized, freely breathing rats. Odor-evoked, respiration-entrained postsynaptic potentials (PSPs) rapidly habituated during a 50-s odor stimulus, then spontaneously recovered within 2 min of odor termination. Associated with the decrease in odor-evoked PSP amplitude was a decrease in the monosynaptic excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation of the LOT. The decrement in LOT-evoked EPSPs recovered with a time course similar to the odor response recovery. These results demonstrate that odor habituation is associated with a decrease in afferent synaptic efficacy in the anterior piriform cortex

Simultaneous recordings of main olfactory bulb (MOB) and anterior piriform cortex (aPCX) neuron responses to repeated and prolonged odor pulses were examined in freely breathing, urethan-anesthetized rats. Comparisons of odor responses were made between multi-unit recordings of MOB activity and single-unit extracellular and intracellular recordings of Layer II/III aPCX neurons. Odor stimuli consisted of either 2-s pulses repeated at 30-s intervals or a single, prolonged 50-s stimulus. Respiration rate was monitored throughout. MOB and aPCX neuron responses to odor were quantified both through firing frequency and through the temporal patterning of firing over the respiratory cycle. The results demonstrate that aPCX neurons habituate significantly more (faster) than MOB neurons with both repeated and prolonged stimulation paradigms. This enhanced habituation is expressed as both a decrease in aPCX firing despite maintained odor-evoked MOB input and as a decrease in aPCX respiratory cycle entrainment despite maintained MOB cyclic input. Intracellular aPCX recordings suggest that several mechanisms may be involved in this experience-induced change in aPCX function, including 1) decreased excitatory driveof aPCX neurons, 2) decreased excitability of aPCX neurons,and/or 3) enhancement in odor-evoked inhibition of aPCX neurons. These studies provide the initial basis for understanding the mechanisms of nonassociative plasticity in olfactory cortex

Single-unit recordings were made from layer II/III anterior piriform cortex (aPCX) neurons in adult Wistar rats to examine odor response patterns to unilaterally and bilaterally delivered stimuli. Isoamyl acetate odor stimulation was presented either unilaterally through tubes inserted into the external nares, or bilaterally during unilateral olfactory bulb lidocaine infusions. Olfactory bulb multiunit or slow-wave activity was recorded simultaneously bilaterally to monitor selectivity of unilateral odor stimulation. The results demonstrate that 1) commissural input to aPCX neurons is sufficient to drive odor responses, and 2) aPCX neurons can be classified on the basis of spatial receptive field type. These receptive fields include cells that respond 1) selectively to ipsilateral stimulation, 2) selectively to contralateral stimulation, 3) to either ipsilateral or contralateral stimulation, and 4) selectively to bilateral stimulation. The potential functions of binaral convergence in the piriform cortex are discussed, and may include enhancement of perceived odor intensity and bilateral access to olfactory memory

Norepinephrine is supplied to both deep and superficial layers of the olfactory bulb through dense projections from the locus coeruleus. Beta-adrenergic receptors are located in nearly all bulb laminae, with high-density foci of beta-1 and beta-2-adrenoceptors present in the glomerular layer. Early olfactory experiences that increase norepinephrine levels in the bulb also decrease the density of beta-1- and beta-2-adrenoceptors, as well as the number of high-density glomerular foci of beta-2-receptors. Changes in bulb norepinephrine levels, therefore, may affect the density of beta-adrenoceptors in the bulb. In the current study, we test this hypothesis by performing unilateral lesions of the locus coeruleus with 6-hydroxydopamine on postnatal day 4, and examining the density of beta-1- and beta-2-adrenergic receptors in the main olfactory bulb of the rat using 125I-labeled iodopindolol receptor autoradiography on postnatal day 19. Locus coeruleus destruction resulted in a statistically significant increase in the density of adrenergic receptors in the ipsilateral bulb compared to the contralateral bulb. Both beta-1- and beta-2-adrenoceptor subtypes increased in density with this manipulation, although the number of glomerular layer high-density beta-2 foci was not significantly different between the two bulbs. These results are consistent with the hypothesis that changes in olfactory bulb norepinephrine can regulate the density of beta-adrenergic receptors in the bulb

Olfactory bulb primary output neurons, mitral/tufted cells, are glutamatergic and excite inhibitory interneurons, granule cells, by activation of both alpha-amino-3-hydroxy-5-methyl-ioxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) glutamate receptors. The data presented here demonstrate that the NMDA antagonists MK-801 and CGP39551, but not ketamine, significantly enhanced expression of c-fos mRNA by mitral cells as measured by in situ hybridization. All three antagonists significantly reduced mitral/tufted cell excitation of granule cells as measured with extracellular field potentials following antidromic stimulation of the lateral olfactory tract (LOT). In turn, the NMDA antagonists significantly reduced granule cell mediated feedback inhibition of mitral/tufted cells, as measured with field potential recordings of paired-pulse LOT stimulation, suppression of mitral/tufted cell single-unit spontaneous activity following LOT stimulation, and intracellularly recorded IPSP amplitude in mitral/tufted cells following LOT stimulation. While there was not a perfect correlation between the effects of the NMDA antagonists on c-fos mRNA expression and on inhibition, the results suggest that disinhibition of mitral/tufted cells accounts for the observed enhancement in c-fos mRNA expression induced by NMDA receptor antagonists

Wistar rats had a single nare occluded on postnatal day 30, depriving the ipsilateral olfactory bulb of odor stimulation. The deprivation lasted for either 1-2 months (short-term) or 12 months (long-term). As previously reported, deprivation greatly reduced tyrosine hydroxylase immunoreactivity (the rate limiting enzyme for dopamine synthesis) in the glomerular layer of the ipsilateral olfactory bulb. The nare was then reopened and odor response patterns of mitral/tufted cells were examined. The proportion of mitral/tufted cell single-units responding to a single odor was enhanced by deprivation. Furthermore, the proportion of mitral/tufted cells responding to more than one odor was increased by deprivation, suggesting a decrease in discrimination. Finally, in undeprived bulbs, the dopamine D2 receptor antagonist spiperone mimicked the effects of deprivation on mitral/tufted cell odor response patterns. The results are interpreted as an activity-dependent dopamine modulation of lateral and feedback inhibition in the olfactory bulb, and are compared with similar events in the dark-adapted retina

Wistar rat pups were trained in an olfactory associative conditioning task on postnatal Day 6, 12, or 20. The training consisted of 20 pairings of a novel odor (peppermint) with footshock (1.5 mA, 1 s) with an intertrial interval of 3 min. Additional pups were trained in either unpaired or naive control conditions. On the day following training, pups were either tested for their behavioral response to the conditioned odor in a two-odor choice test, or injected with 14C-2-deoxyglucose and exposed to the odor for examination of olfactory bulb neural responses to the odor. The results demonstrate that, although pups at all ages learned to avoid the odor, only pups trained during the first postnatal week had a modified olfactory-bulb glomerular-layer response to the odor. These results suggest that although olfactory memory is correlated with modification of olfactory bulb glomerular layer function in newborns, these changes are not required for normal memory in older pups