Analysis Tools
behavior/neurological
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• mice show increased susceptibility to induced seizures with the adenosine A1 receptor antagonist DPCPX, and a single high dose of DPCPX consistently triggers lethal status epilepticus in mutants but not controls
• pretreatment with antagonists to adenosine A2a receptor (SCH58261) and TrkB (Ana-12) significantly extend the survival time after DPCPX-induced seizures
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• associative learning in the conditioned freezing paradigm is decreased during conditioned stimulus 2
• however, the percentage time freezing during conditioned stimulus 3 and 4 is increased compared with baseline conditioned stimulus 1 freezing indicating that mice show a general ability to learn
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• mice show a deficit in contextual memory with freezing rates comparable to baseline
• however, mutants show no differences from controls in the elevated plus maze, acoustic startle response, or spatial working memory and the response to foot shock is normal
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• from 2 months of age, mice exhibit increased susceptibility to stress-induced seizures (placement in novel environment) which are characterized by tonic-clonic convulsions
• by 3 months of age, 44% of mutants react with a seizure when placed into a novel environment, by 4 months, seizure incidence is 89% and by 6 months, 100%
• the probability of an evoked seizure response rises from 7.4% at 2 months to 77% at 6 months
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• EEG recordings indicate spontaneous seizures with average seizure rate of 0.85 seizures per day and average duration of 43.6 +/- 7.4 seconds
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nervous system
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• mice show increased susceptibility to induced seizures with the adenosine A1 receptor antagonist DPCPX, and a single high dose of DPCPX consistently triggers lethal status epilepticus in mutants but not controls
• pretreatment with antagonists to adenosine A2a receptor (SCH58261) and TrkB (Ana-12) significantly extend the survival time after DPCPX-induced seizures
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• from 2 months of age, mice exhibit increased susceptibility to stress-induced seizures (placement in novel environment) which are characterized by tonic-clonic convulsions
• by 3 months of age, 44% of mutants react with a seizure when placed into a novel environment, by 4 months, seizure incidence is 89% and by 6 months, 100%
• the probability of an evoked seizure response rises from 7.4% at 2 months to 77% at 6 months
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• EEG recordings indicate spontaneous seizures with average seizure rate of 0.85 seizures per day and average duration of 43.6 +/- 7.4 seconds
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• mice have increased adenosine A2a receptor-mediated synaptic plasticity
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• mice have increased levels of synaptic adenosine
• treatment of hippocampal slices from epileptic mutants with the adenosine A1 receptor antagonist DPCPX results in a higher disinhibition of synaptic transmission than controls
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• maximum fEPSP slope is higher in mutant hippocampal slices than in controls
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• hippocampal slices show an increase in theta-burst-induced LTP magnitude
• treatment with the adenosine A2a receptor-selective antagonist SCH58261resverses the LTP magnitude
• treatment with the tyrosine kinase inhibitor K25a abolishes the increased LTP magnitude
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