UVM Theses and Dissertations
Format:
Print
Author:
Zhang, Peng
Dept./Program:
Biology
Year:
2007
Degree:
PhD
Abstract:
Located at the anterior portion of the nose, mouse vomeronasal organs (VNOs) detect odors and pheromones. These odor responses appear to be transduced through phospholipase C (PLC), activation of which elevates DAG. DAG activates a ca²- permeable channel, TRPC2 channel (transient receptor potential channel, subfamily C, member 2), leading to depolarization of neurons. DAG is hydrolyzed to arachidonic acid (AA) through a DAG lipase. AA has been suggested to play a role in odor transduction in vomeronasal neurons. However, the pathways AA mediates have not been studied in detail.
We studied the role for AA in odor transduction in mouse vomeronasal neurons with electrophysiology, imaging and imrnunocytochemistry techniques. Our data suggested that AA can play a dual role in odor transduction: (1) AA plays an excitatory role by activating Ca²-activated nonselective cation ion (CaNS) channels. CaNS channels allow the influx of Na⁺/Ca²⁺ that depolarizes the membrane potential, mediating an excitatory pathway. Therefore, there are two excitatory pathways when an odorant activates PLC: DAG activates TRPC2 channels and AA activates CaNS channels. The existence of the two excitatory pathways might lead to a high amplification of the signal transduction, thus making it possible to detect very low concentration of odorants. In addition, our data suggest AA activates CaNS channels directly, rather than through its downstream metabolites; (2) AA also mediates an inhibitory pathway by activating a large-conductance Ca²⁺-activated K⁺ (BK) channel.
Using immunocytochemistry, we have shown BK channels were specifically expressed in the dendrites and somata of vomeronasal neurons. A repetitive application of AA activated the BK current, which inhibited the firing of the vomeronasal neurons. We propose that this inhibitory pathway would be only activated upon a prolonged exposure to odors. Thus, the activation of BK channels by AA might be a mechanism-underlying the odor adaptation. Odor adaptation would limit excessive Ca² influx and could prevent neuron damage. Furthermore, we studied the mechanism of BK channel activation. We found that, opposite from CaNS channels, BK channels were not directly activated by AA. Only the metabolites of 12-lipoxygeanse (12-LO) activated BK channels. Due to the steps in AA metabolization, the activation of BK channels should be slower than the activation of CaNS (by AA directly). Collectively, our data suggest AA sequentially activates the excitatory pathway and the inhibitory pathway.
Moreover, we studied the neuromodulatory role for gonadotropin-releasing hormone (GnRH) in vomeronasal neurons. We found the expression of GnRH receptors (GnRHrs) in the vomeronasal neurons, thus GnRH may modulate the odor responses through the GnRHr-coupled signal transduction pathways. In our preliminary data, we found GnRH selectively inhibited the action potential firing in most neurons, while in a small subset of neurons GnRH increased the number of action potentials. In addition, GnRH induced an inward current through PLC pathway, which is very similar to odorinduced responses. Although the mechanisms of these observations need further investigation, our preliminary data suggest GnRH differently modulates the odor responses in different populations of vomeronasal neurons.
We studied the role for AA in odor transduction in mouse vomeronasal neurons with electrophysiology, imaging and imrnunocytochemistry techniques. Our data suggested that AA can play a dual role in odor transduction: (1) AA plays an excitatory role by activating Ca²-activated nonselective cation ion (CaNS) channels. CaNS channels allow the influx of Na⁺/Ca²⁺ that depolarizes the membrane potential, mediating an excitatory pathway. Therefore, there are two excitatory pathways when an odorant activates PLC: DAG activates TRPC2 channels and AA activates CaNS channels. The existence of the two excitatory pathways might lead to a high amplification of the signal transduction, thus making it possible to detect very low concentration of odorants. In addition, our data suggest AA activates CaNS channels directly, rather than through its downstream metabolites; (2) AA also mediates an inhibitory pathway by activating a large-conductance Ca²⁺-activated K⁺ (BK) channel.
Using immunocytochemistry, we have shown BK channels were specifically expressed in the dendrites and somata of vomeronasal neurons. A repetitive application of AA activated the BK current, which inhibited the firing of the vomeronasal neurons. We propose that this inhibitory pathway would be only activated upon a prolonged exposure to odors. Thus, the activation of BK channels by AA might be a mechanism-underlying the odor adaptation. Odor adaptation would limit excessive Ca² influx and could prevent neuron damage. Furthermore, we studied the mechanism of BK channel activation. We found that, opposite from CaNS channels, BK channels were not directly activated by AA. Only the metabolites of 12-lipoxygeanse (12-LO) activated BK channels. Due to the steps in AA metabolization, the activation of BK channels should be slower than the activation of CaNS (by AA directly). Collectively, our data suggest AA sequentially activates the excitatory pathway and the inhibitory pathway.
Moreover, we studied the neuromodulatory role for gonadotropin-releasing hormone (GnRH) in vomeronasal neurons. We found the expression of GnRH receptors (GnRHrs) in the vomeronasal neurons, thus GnRH may modulate the odor responses through the GnRHr-coupled signal transduction pathways. In our preliminary data, we found GnRH selectively inhibited the action potential firing in most neurons, while in a small subset of neurons GnRH increased the number of action potentials. In addition, GnRH induced an inward current through PLC pathway, which is very similar to odorinduced responses. Although the mechanisms of these observations need further investigation, our preliminary data suggest GnRH differently modulates the odor responses in different populations of vomeronasal neurons.