Analysis Tools
nervous system
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• mice show increased sensitivity to bicuculline-induced seizures even at low level blockade of GABA transmission with 2 mg/kg bicuculline, unlike similarly treated wild-type controls
• at higher bicuculline doses (3 or 4 mg/kg), mice exhibit a significantly higher seizure score and number of seizure episodes and deaths than similarly treated wild-type controls
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• mice exhibit a significantly higher seizure score and number of seizure episodes in response to startling sound or to combined sound + odorant (octanol) stimuli relative to wild-type controls
• administration of VU0155041 has no effect on seizure score but significantly reduces the number of episodes and the average length of each episode, with no apparent effect on wild-type controls
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• mice exhibit selective downregulation of all brain group III metabotropic glutamate receptors (mGluRs) that ELFN2 associates with, including mGluR4, mGluR7 and mGluR8, resulting in augmented excitatory synaptic transmission in the hippocampus
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• when field excitatory post-synaptic potentials (fEPSPs) are recorded from the stratum radiatum of CA1 in response to stimulated glutamate release from Schaffer collaterals of CA3, mice show a striking increase in both amplitudes and slopes of fEPSPs across a range of stimulation intensities relative to wild-type controls
• however, analysis of fiber volley amplitude versus stimulus intensity indicates normal synaptic architecture
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behavior/neurological
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• mice show increased sensitivity to bicuculline-induced seizures even at low level blockade of GABA transmission with 2 mg/kg bicuculline, unlike similarly treated wild-type controls
• at higher bicuculline doses (3 or 4 mg/kg), mice exhibit a significantly higher seizure score and number of seizure episodes and deaths than similarly treated wild-type controls
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• despite an increased number of center crossings, mice spend significantly less time in the center and more time wall-hugging than wild-type controls in the open field test
• mice spend significantly less time than wild-type controls in open arms of the elevated plus maze test
• mice exhibit increased stereotypic, repetitive behaviors including grooming and rotations in the open field test
• mice exhibit a significantly number of marbles buried than wild-type controls in the marble-burying test
• administration of VU0155041 increases the time spent in the center of the open field test and reduces the number of rotations and time spent grooming, with no apparent effect on wild-type controls
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• in the open field test, mice spend more time wall-hugging (thigmotaxis) than wild-type controls
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• in a 30-min window of the open field test, mice spend more time performing stereotypic grooming behavior than wild-type controls
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• mice are markedly hyperactive in the open field test, as shown by significant increase in total distance traveled as well as average speed
• mice spend more time ambulating and less time staying immobile than wild-type controls; however, habituation rate for distance traveled and % of time spent freezing in the open field test are normal
• group III mGluR augmentation using positive allosteric modulator VU0155041 completely rescues the hyperactive phenotype, with no apparent effect on wild-type controls
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• in the open field test, mice exhibit increased stereotypic, repetitive behaviors including grooming and rotations, suggesting increased anxiety and compulsivity
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• in the social novelty paradigm, mice spend comparably less time with both familiar and novel mice, preferring to reside in the uninhabited center chamber rather than exploring the novel mouse chamber
• in a three-chamber social interaction test, mice spend more time in the empty chamber rather than exploring the novel mouse chamber
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• mice exhibit a significantly higher seizure score and number of seizure episodes in response to startling sound or to combined sound + odorant (octanol) stimuli relative to wild-type controls
• administration of VU0155041 has no effect on seizure score but significantly reduces the number of episodes and the average length of each episode, with no apparent effect on wild-type controls
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