**ABSTRACT NOT FOR CITATION WITHOUT AUTHOR PERMISSION. The title, authors, and abstract for this completion report are provided below.  For a copy of the full completion report, please contact the author via e-mail at zielin1@uwindsor.ca or via telephone at 519-253-3000 x2726. Questions? Contact the GLFC via email at frp@glfc.org or via telephone at 734-662-3209.**




 Barbara Zielinski¹, Réjean Dubuc²


¹Department of Biological Sciences, University of Windsor, Windsor, Ontario.


²Groupe de Recherche en Activité Physique Adaptée, Department of Kinesiology, Université du Québec à Montréal, Montréal, Québec


³Groupe de Recherche sur le Système Nerveux Central, Department of Neuroscience, Université de Montréal, Montréal, Québec.


December 2015




Essential behaviors such as migration, reproduction, and feeding are driven by olfactory cues in the sea lamprey (reviewed in 6, 7, and 8). In 2010, we uncovered the neural substrate underlying olfactory-motor behavior in lampreys [Derjean et al. 2010 PLoS Biol 8(12): e1000567]. This consists of a specific neural pathway, extending from the medial part of the olfactory bulb (OB) to the mesencephalic locomotor region, with a single relay in the posterior tuberculum. This oligosynaptic pathway is dedicated to action by generating rapid motor responses to olfactory stimuli. The modulatory mechanisms that act on this pathway and that are responsible for the variability of behavioral responses of lampreys to olfactory inputs, are still unknown. We addressed this question by using anatomical (tracers and immunohistochemistry) and physiological (intracellular recordings) techniques. During the granting period, we focused our investigation on modulatory mechanisms acting on the OB, the point where olfactory sensory neurons enter the central nervous system, and where projection neurons extend to other brain regions. We examined GABA modulation in the OB (5). GABAergic neurons and fibers are present throughout the OB, including the medial OB, a central component of the olfactory-locomotor pathway, suggesting a role for GABA in the modulation of this pathway. Physiological experiments showed that this pathway was indeed strongly inhibited by endogenous GABA.  Likewise, endogenous GABA attenuated OB responses to odors, including pheromones.  Surprisingly, we found that olfactory inputs from the lateral OB were also capable of activating a descending motor pathway when GABA inhibition was removed. This finding led to the discovery of a secondary olfactomotor pathway. We will submit a paper describing these results to the high impact factor journal PLoS Biology (5). This newly-uncovered glutamatergic pathway relays olfactory inputs from the lateral OB to brainstem locomotor control centers via the lateral pallium and the posterior tuberculum. Our findings indicate that this pathway will contribute significantly to the motor responses of lampreys to olfactory stimulation in their environment as our previously discovered primary medial olfactomotor pathway. We also showed that the distribution and morphology of the OB projection neurons associated with the primary (medial) and secondary (lateral) olfactomotor pathways are different (1), as are the odor response profiles of these two regions (2). We also investigated the modulation of the OB neuron responses to the application of odors to the peripheral olfactory organ (3, 4). We found that OB responses to the reproductive pheromone, 3KPZS, are potentiated by estradiol. The olfactory responses to this pheromone were stronger in animals that were treated with estradiol. (3). Distributed throughout the olfactory nerve and OB are serotonergic (5-hydroxytryptamine; 5-HT) fibers. We found that the 5-HT system modulates odor responses, as the application of 5HT1a antagonists increased the amplitude of the olfactory response to all tested odors, suggesting that endogenous 5HT attenuates olfactory responses in both the medial and lateral region of the OB (4). We are preparing a publication on these results, as well. Therefore, the hormonal changes that take place during sexual maturation, as well as endogenous neurotransmitters GABA and serotonin are key players in modulating olfactory-locomotor behavior in the sea lamprey.