Study On The Effect Of B-cell CLL/lymphoma 9 Gene On Cortical Neurons Electrophysiological Properties

B-cell CLL/lymphoma 9 gene was located at the chromosome 1 in human and chromosome 3 in mice.Recent study showed that dysfunction of BCL9 gene could induce schizophrenia,epilepsy,diporlor disorder and autism.However,there was no research on the function of BCL9 in the brain.To develop the function of BCL9 in the brain,we use whole-cell patch clamp to study the effect of BCL9 on neuronal electrophysiology properties.First,we explored the electrophysiological properties of cortical neurons in the neonatal mice.Three classes of firing paterrns were distinguished: tonic firing,phasic firing,and single spiking.We compared the difference of neuronal passive and active properties in different action potential patterns,and found that: 1)There are significant differences in the voltage dependent inward current and the outward current in nurons with different firing patterns.Tonic firing neurons showed the largest amplitude,followed by phasic firing neurons,single spike neurons showed the weakest.2)The rheobase of tonic neurons was lower than that of single neurons.3)On the morphological analysis of action potential,there were significant differences among different action potential firing patterns on time rise and duration.4)There were no significant differences in the passive properties of neurons among different action potential firing patterns.The results showed that there were significant differences among the three action potential firing patterns in the active properties of neurons,and voltage dependent sodium current and potassium current may play an important role in the generation of firing patterns.In the study of effects of BCL9 knockdown on the passive and active electrophysiological properties of cortical neurons at postnatal 3 days,we found that: 1)BCL9 knockdown significantly increased the voltage dependent transient sodium currents and had no significant effect on the voltage dependent outward current;2)BCL9 knockdown changed the action potential firing patterns,and decreased the number of action potential;3)BCL9 knockdown shortened the rise time of action potential.4)BCL9 knockdown had no significant effect on sEPSC and mEPSC and the membrane passive properties.The results showed that the voltage dependent sodium current was increased in BCL9 knockdown mice at postnatal 3 days,which increased the excitability of neurons.In the study of effects of BCL9 knockout on the passive and active electrophysiological properties of cortical neurons at postnatal 3 days,we found that: 1)BCL9 knockout significantly increased the voltage dependent transient sodium currents and sustained outward current.3)BCL9 knockout reduced the action potential firing number,4)but made no change on action potential characteristics and membrane passive properties.Thses results showed that BCL9 significantly increased the voltage dependent sodium current and potassium current.From the results,it can be seen that the BCL9 protein plays an important role in maintaining neuronal physiological characteristics.In this experiment,the effect of BCL9 on the electrophysiological properties of neurons was first explored.It is important to further explore the function of BCL9 in brain and the pathogenesis of mental disorders.