behavior/neurological
• in the Morris water maze, 6-7 and 9-10 month old, but not 3-4 month old, mice show decreased crossing plate times in the probe trial indicating that spatial discrimination learning impairments begin at 6-7 months of age
|
• in the Morris water maze, 6-7 and 9-10 month old, but not 3-4 month old, mice require longer to find the platform, indicating that spatial memory impairments begin at 6-7 months of age
|
• in the buried food test, mice need more time to find the hidden food than wild-type mice indicating impaired olfactory performance
• in the olfactory discrimination test, mice show decreases in the numbers of correct olfactory discrimination responses per trial at 3-4 months, 6-7 months, and 9-10 months of age
|
homeostasis/metabolism
• mice show a gradual increase in the amount, degree of aggregation, and spatial distribution of amyloid beta deposits from the outer to the inner layers of the olfactory bulb with increasing age
|
nervous system
• mice show a gradual increase in the amount, degree of aggregation, and spatial distribution of amyloid beta deposits from the outer to the inner layers of the olfactory bulb with increasing age
|
• the dendritic spine density of granule cells is reduced in the olfactory bulb
|
• mice exhibit a wider synaptic cleft in the external plexiform layer
• however, laminar organization of the olfactory bulb is normal
|
• immature spine density tends to decline at 3-4 and 6-7 months of age and is reduced at 9-10 months of age
• the dendritic spine density of granule cells is reduced in the olfactory bulb
• mature spine density is the same as in wild-type mice at 3-4 months of age but is decreased in 6-7 and 9-10 month old mice
|
• the presynaptic and postsynaptic membrane structures of asymmetric synapses (excitatory synapses) in the olfactory bulb are damaged
|
• thickness of the postsynaptic density in olfactory bulb asymmetric synapses is thinner in 3-4, 6-7, and 9-10 month old mice
|
• mice exhibit a wider synaptic cleft in the external plexiform layer of symmetric synapses
|
• synaptic vesicles of olfactory bulb asymmetric synapses exhibit unclear and broken membrane structure and blurred boundaries at 6-7 and 9-10 months of age
|
• mitral cells in 3-4 and 9-10 month old mice exhibit a higher spontaneous firing rate of spontaneous action potential indicating the hyperactivation of mitral cells
|
• 3-4 and 9-10 month old mice exhibit increased gamma, low-gamma, and high-gamma oscillations and firing rates of mitral cells in the olfactory bulb external plexiform layer
• local application of the GABA(A)R agonist muscimol nearly abolishes the aberrant increase in gamma oscillations in the external plexiform layer at advanced stages of disease while a GABA(A)R antagonist bicuculline increased the gamma oscillations
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
Alzheimer's disease | DOID:10652 | J:275175 |