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Givaudan-Roure Lecture - Association for Chemoreception Sciences

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5 Slide [ ] Olfactory Bulb Physiology<br />

MAIN OLFACTORY BULB DETECTION OF SOCIAL<br />

RECOGNITION CUES IN MOUSE URINE<br />

Lin D. 1, Katz L.C. 1 1Neurobiology, Duke University, Durham, NC<br />

In rodents, chemicals present in urine play a critical role in<br />

reproductive behaviors and mediating aggressive interactions. Both<br />

behavioral tests and immediate early gene expression indicate that the<br />

main olfactory bulb (MOB) participates in individual identification.<br />

Little is known about how urine responsive neurons are organized in the<br />

MOB, or which semiochemicals in urine carry important in<strong>for</strong>mation.<br />

To address these issues, we examined extracellular activity of mitral<br />

cells in the mouse MOB in response to volatile components of urine<br />

from different sexes and strains of mice. Recordings from more than<br />

one thousand cells revealed that less than 5% of neurons responded<br />

selectively to different sources of urine. The urine responsive cells were<br />

confined to a small region in the ventral and lateral parts of the MOB.<br />

To ascribe a role to specific chemicals present in urine, we combined<br />

gas chromatography with extracellular recording in the MOB, so that<br />

the activity of individual mitral cells could be monitored while<br />

delivering the separated urinary components. The majority of neurons<br />

which showed an excitatory response to complete urine responded<br />

identically to just a single peak out of the hundreds present in the gas<br />

chromatogram of mouse urine. Surprisingly, over 20% of the urine<br />

responsive cells responded to one particular component, which has been<br />

implicated as a mouse pheromone. Preliminary behavioral data indicate<br />

the concentration of this pheromone in male mouse urine significantly<br />

correlates with the duration of female mice investigation of the urine.<br />

Thus, mitral cells selectively respond to individual components in<br />

mouse urine, and a disproportionate number of these neurons are<br />

involved in detecting a volatile pheromone.<br />

6 Slide [ ] Olfactory Bulb Physiology<br />

SPATIO-TEMPORAL FIRING RATE INTERACTIONS<br />

AMONGST AN ENSEMBLE OF MITRAL/TUFTED CELLS<br />

MAY SUBSERVE ODORANT DISCRIMINATIONS.<br />

Lehmkuhle M.J. 1, Normann R.A. 1, Maynard E.M. 1 1Bioengineering,<br />

University of Utah, Salt Lake City, UT<br />

Populations of output neurons in the mammalian olfactory bulb (OB)<br />

exhibit distinct spatial and temporal activation patterns when stimulated<br />

with enantiomers of the same odorant. If, as has recently been<br />

suggested, a two-stage network of inhibitory and excitatory centersurround<br />

connections link spatially distributed glomerular activity with<br />

underlying mitral and tufted neurons within olfactory bulb, then it is<br />

likely that these interactions affect the ensemble response to odorant<br />

stimulation. Here we investigate in the anesthetized rat the rate<br />

response temporal kinetics in neuronal ensembles by comparing pairwise<br />

response similarity of a population of single- and multi-unit<br />

mitral/tufted cells aligned to breathing in the presence and absence of<br />

enantiomers of limonene. Such comparisons can be used to quantify<br />

differences in the kinetics of the response of one neuron from other<br />

neurons in the recorded population. It is shown that aligning unit<br />

responses to the inhalation phase of the animals´ breathing tends to<br />

synchronize unit responses. Instances of high-similarity and<br />

dissimilarity within the population are enantiomer-specific with these<br />

instances occurring <strong>for</strong> pairs of units recorded over electrode<br />

separations of 400 µm – 1.7 mm. These results support the centersurround<br />

hypothesis and indicate that spatio-temporal firing rate<br />

interactions amongst an ensemble of OB neurons produce odorant<br />

representations beyond simple firing rates that may subserve odorant<br />

discrimination.<br />

2<br />

7 Slide [ ] Olfactory Bulb Physiology<br />

PRESYNAPTIC CENTER-SURROUND INHIBITION SHAPES<br />

ODORANT-ELICITED INPUT TO THE MOUSE OLFACTORY<br />

BULB<br />

Vucinic D. 1, Cohen L.B. 1, Kosmidis E. 1 1Cellular & Molecular<br />

Physiology, Yale University, New Haven, CT<br />

Synaptic transmission from olfactory primary afferents onto neurons<br />

of the olfactory bulb is modulated by presynaptic GABA receptors<br />

B<br />

(e.g. Wachowiak and Cohen, 1999; Ennis et al., 2001; Wachowiak et<br />

al., 2002). To study the role of this modulatory circuit in vivo we<br />

recorded the fluorescent signal from Calcium Green-1 dextran, loaded<br />

into the axon terminals of olfactory receptor neurons, in response to<br />

odorant presentations to the nose. We bath-applied agonists and<br />

antagonists of the GABA receptor onto the olfactory bulb and looked<br />

B<br />

<strong>for</strong> an effect of these agents on the amplitude, spatial map and time<br />

course of odorant-elicited signals. The GABA antagonist CGP46381<br />

B<br />

caused a significant and long-lasting increse in the average amplitude of<br />

glomerular activation in most preparations. Large changes in signal<br />

amplitude were accompanied by a change in the input map such that<br />

many weakly activated glomeruli underwent relatively larger increases<br />

in signal amplitude than the strongy activated ones. We find that the<br />

magnitude of this effect correlates with how strongly activated the<br />

surround of a glomerulus is. This finding indicates that a <strong>for</strong>m of<br />

GABA-mediated center-surround inhibition modifies the sensory input<br />

map even be<strong>for</strong>e the first synaptic transmission, increasing its contrast.<br />

Supported by NIH grants NS07455 and DC05259.<br />

8 Slide [ ] Olfactory Bulb Physiology<br />

LONG-TERM ODOR EXPOSURE INCREASES SURVIVAL<br />

AND FUNCTIONAL INTEGRATION OF INTERNEURONS IN<br />

THE OLFACTORY BULB.<br />

Mirich J. 1, Illig K.R. 1, Brunjes P.C. 1 1Psychology, University of<br />

Virginia, Charlottesville, VA<br />

While our previous work indicates that activity is critical <strong>for</strong> the<br />

survival of bulbar interneurons, the rules by which new neurons become<br />

integrated into existing neural circuits remain unclear. If olfactory<br />

activity guides the functional integration and survival of newly born<br />

cells, then repeated exposure to an odorant should increase the number<br />

of cells that participate in the coding of that odor. Adult subjects<br />

received daily injections of BrdU <strong>for</strong> 5 days to label a cohort of newly<br />

born neurons. They were then exposed daily to menthyl isovalerate, ßpinene,<br />

butyric acid, or mineral oil (control) <strong>for</strong> 3 weeks. For half of the<br />

animals in each group, the odorant was paired with Froot Loops to<br />

increase salience. On the last day, animals were exposed to ultra-pure<br />

odorants intermittently <strong>for</strong> 1hr, and tissue stained <strong>for</strong> BrdU and Fos<br />

protein. Long-term odor exposure doubled the survival of interneurons<br />

compared with controls. Double-label immunohistochemistry showed a<br />

statistically significant increase (44%; p < 0.05) in BrdU/Fos positive<br />

cells, demonstrating integration of newly born cells during the training<br />

period. Additional analyses confirmed that new neurons integrated<br />

specifically into the areas of the bulb activated by the odorant<br />

presented. This study demonstrates that survival and integration of<br />

newly born bulbar neurons depends on the odor environment present<br />

during their development. We conclude that repeated activation of<br />

synaptic ensembles might change neural requirements, thereby<br />

influencing the cellular milieu. Supported by NIH grants DC0338<br />

(NIDCD) and HD07323 (NICHD).

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