All Phenotypes Kcnt1<em8Frk> MGI Mouse

N

• normal brain size and gross morphology

• normal V-rest, R-in and action potential (AP) threshold levels and AP half-width, AP repolarization rate, afterhyperpolarization (AHP), and AP firing response to incremental current injections in cultured glutamatergic cortical neurons

• normal R-in and rheobase in glutamatergic cortical neurons in brain slices

• normal excitatory postsynaptic currents (ePSCs) for all combinations (I-I, E-E, E-I, I-E) of excitatory (E) and inhibitory (I) cultured cortical neurons

• normal spontaneous inhibitory postsynaptic currents (sIPSCs) in cultured GABAergic and glutamatergic cortical neurons

• normal spontaneous postsynaptic current (sPSC) amplitudes and kinetics in cultured GABAergic and glutamatergic cortical neurons

seizures ( J:300699 )

• 87% of mice have at least one spontaneous seizure during 38 h observation

• ~2x higher incidence of seizures during light-on (sleep) period than dark (active) period

• 90% of seizures occur during NREM sleep

tonic seizures ( J:300699 )

• TSs lasting 1-2 sec, often preceding GTCSs but also alone or in clusters seconds apart

tonic-clonic seizures ( J:300699 )

• generalized tonic-clonic seizures (GTCSs) of 30-60 sec

abnormal nervous system morphology ( J:300699 )

• increased homotypic synaptic connectivity amongst cultured glutamatergic (excitatory [E]) and amongst GABAergic (inhibitory [I]) cortical neurons

• increased excitatory/inhibitory (E/I) ratio amongst cultured glutamatergic cortical neurons

• normal E/I ratio amongst cultured GABAergic cortical neurons

abnormal glutaminergic neuron morphology ( J:300699 )

• more depolarized action potential (AP) threshold in cortical neurons in brain slices

• normal AP firing patterns

abnormal GABAergic neuron physiology ( J:300699 )

• increased rheobase current in cultured fast spiking (FS) cortical neurons

• incremental current injections showed a decrease in number of APs per current step in cultured NFS cortical neurons and NFS cortical neurons in brain slices

• decreased R-in, increased rheobase current and membrane capacitance (C-m), narrower action potential (AP) half-width, faster AP repolarization and larger afterhyperpolarization (AHP) in cultured non-fast spiking (NFS) cortical neurons

• decreased R-in and increased rheobase current and membrane capacitance (C-m) in non-fast spiking (NFS) cortical neurons in brains slices

• normal V-rest, R-in and action potential (AP) threshold levels and AP half-width, AP repolarization rate and afterhyperpolarization (AHP) in cultured fast spiking (FS) cortical neurons

• normal AP half-width and AHP in NFS cortical neurons in brains slices

• normal V-rest and action potential (AP) threshold levels in cultured non-fast spiking (NFS) cortical neurons

abnormal CNS synaptic transmission ( J:300699 )

• increased spontaneous excitatory postsynaptic current (sEPSC) frequency in cultured glutamatergic and cultured non-fast spiking (NFS) GABAergic cortical neurons

behavior/neurological phenotype ( J:300699 )

N	• normal behavior in elevated plus maze test

impaired contextual conditioning behavior ( J:300699 )

• decreased freezing behaviors

• normal post-shock freezing behavior and acoustic startle responses

impaired cued conditioning behavior ( J:300699 )