|Budget Amount *help
¥7,400,000 (Direct Cost : ¥7,400,000)
Fiscal Year 1997 : ¥2,900,000 (Direct Cost : ¥2,900,000)
Fiscal Year 1996 : ¥4,500,000 (Direct Cost : ¥4,500,000)
Female mice form an olfactory memory of the pheromones of the male with which they mate. This olfactory memory is of critical biological importance, because it prevents any subsequent exposure to this male's pheromones from initiating neuroendocrine mechanisms that would terminate pregnancy. Pheromones from strange males, for which no memory has been formed, induce pregnacy block by activating the accessory olfactory system by way of the vomeronasal receptors. Memory formation depends on cervicovaginal stimulation at mating, but requires a prolonged exposure of 4 to 6 h to male phernomones immediately after mating. The memory formation depends on mating-induced activation of noradrenergic terminals in the accessory olfactory bulb (AOB), the first relay in the accessory olfactory pathway. This memory lasts for at least 30 days following mating. The synaptic changes underlying this memory formation occur in the AOB.
In the AOB,mitral cells, when activated by vomeronasal nerve inputs, depo
larize granule cells by means of glutamate released at the dendrodendritic synapses. This depolarization releases gamma-aminobutyric acid from the granule cells which in turn hyperpolarize the mitral cells. Recent studies have implicated the mitral-to-granule dendrodendritic synapse in the formation of the memory. In this study we have obtained the following results.
1.Exogenous administration of nitric oxide can induce a pheromone-specific olfactory memory without mating, and that this memory is mediated, at least in part, by noradrenaline. In addition, activation of endogenous nitric oxide synthase activity produces the same effect.
2.In collaboration with Drs.Ichikawa, Mori and Matsuoka, we demonstrate that the size of the mitral-to-granule asymmetrical synapse is significantly larger in the group that has formed the memory than in the group that has not formed the memory.
3.We have previously demonstrated that activation of mGluR2, a metabotropic glutamate receptor, in the AOB permits the formation of a pheromone-specific memory. Preliminary experiments suggest impairment of the olfactory memory in mice lacking mGluR2. Less