Analysis Tools
behavior/neurological
|
• when mice are dropped supine from height of 50 cm, mutants show poor air-righting performance, whereas control mice land on their feet ~100% of the time and toxin-treated normal controls land feet-first on ~50% of tests
• when placed inside a tube and inverted to supine position, mutants remain inverted for duration (60 s) of test whereas controls right themselves within a few seconds
• after 30 minutes of intermittent horizontal rotation, control mice display a significant decrease in spontaneous movement, but mutants do not show a decrease
|
|
• mutants lack the acoustic startle reflex (ASR), but startle reflex to somatic sensory stimuli such as air puffs is intact
|
|
• mutants can only stay on the grid for 60 seconds, coinciding with the turn to 90 degrees, in a cling test; control mice can hang on to the grid for ~180 seconds, including complete inversion of the grid
• in the rotarod test, mutants and drug-treated control mice fall off the rod immediately, often before it begins to move, whereas normal controls can walk for ~the full 5 minute test period
|
|
• mutants cannot keep their heads above water during swimming and rapidly begin a spiraling motion underwater and drown if not rescued
|
hyperactivity
(
J:91987
)
|
• in photocell activity chambers, mutants display 3-4-fold higher activity compared to control mice while vestibular toxin-treated controls have 10-fold increased activity
|
|
• stereotypic behaviors like circling or abnormal head movements, are evident in all mutants at 2-3 weeks of age, and persist throughout observation period (>1 year)
|
head bobbing
(
J:91987
)
|
• in open field tests, mutants display rapid vertical bobbing head movements
|
head shaking
(
J:91987
)
|
• mice show rapid sideways wagging movements of the head during open field tests
|
head tossing
(
J:91987
)
|
• mice show occasional episodes of exaggerated and sustained, elevation of the head, resembling retrocollis, during open field observations
|
|
• in open field test, mice exhibit circling to the left or right; controls do not while in vestibular toxin-treated normal controls, circling is exacerbated compared to mutants
|
hearing/vestibular/ear
|
• vacuole-like defects measuring 15-25 um are seen in the vestibular epithelium
• cells are disorganized in sensory epithelium; some supporting cell nuclei lose contact with the basement membrane and occupy locations higher in the epithelium
|
|
• afferent nerve calyces surrounding type I hair cells lack the fullness and rich mitochondrial content seen in controls; large vacuole-like defects appear to be localized inside afferent calyces
• these vacuoles are surrounded by normal but small and crowded mitochondria and contain scanty debris like cytosol or mitochondria
|
|
• crista show a reduction density of hair cells compared to controls
|
|
• ABR thresholds for click as a stimulus are normal, with a trend toward increased thresholds for 8 and 16 kHz tone stimuli in mutants (not reaching significance, though)
|
nervous system
|
• vacuole-like defects measuring 15-25 um are seen in the vestibular epithelium
• cells are disorganized in sensory epithelium; some supporting cell nuclei lose contact with the basement membrane and occupy locations higher in the epithelium
|
|
• afferent nerve calyces surrounding type I hair cells lack the fullness and rich mitochondrial content seen in controls; large vacuole-like defects appear to be localized inside afferent calyces
• these vacuoles are surrounded by normal but small and crowded mitochondria and contain scanty debris like cytosol or mitochondria
|
|
• global loss of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepripionic acid (AMPA) receptors in nucleus reticularis and a selective loss at corticothalamic synapses in inhibitory neurons of the nucleus reticularis thalamus
• however, no loss of AMPA receptors is seen at corticothalamic synapses in excitatory relay neurons in the thalamic ventral posterior region
|
|
• there are more parallel fiber- Purkinje spine synapses with smaller presynsaptic terminal compared to the postsynaptic spine
• there is a 43% reduction in the mean area of the presynaptic terminals in mutants
• synaptic profile in wild-type shows >80% of synapses having larger parallel fiber varicosities than postsynaptic Purkinje cell spines, while in mutants there is ~equal distribution of synapses with larger parallel fiber area than postsynaptic Purkinje cell spine, those with equal pre- and postsynaptic areas, or with smaller parallel fiber varicosity than the postsynaptic Purkinje cell spine
|
|
• synaptic size appears smaller
|
|
• mutants have lower synaptic density in the cerebellar cortex; there are 25% fewer synapses compared to wild-type
|
|
• selective loss of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepripionic acid (AMPA) receptors at corticothalamic synapses in inhibitory neurons of the nucleus reticularis thalamus
|
|
• presynaptic vesicles are less dense compared to wild-type
|
|
• presynaptic vesicles are reduced in number
• there are fewer docked vesicles and fewer vesicles adjacent to the active zone ready to dock in mutants than in wild-type
|
|
• saline-treated mutants display frequent abnormal polyspike discharges in the EEG; however, these do not correlate temporally with dyskinetic behaviors
• after nifedipine treatment, polyspike discharges are increased while reducing dyskinesia scores in mutants; an inverse relationship is observed
|
cellular
|
• presynaptic vesicles are less dense compared to wild-type
|
|
• presynaptic vesicles are reduced in number
• there are fewer docked vesicles and fewer vesicles adjacent to the active zone ready to dock in mutants than in wild-type
|
