Neuronal stimulation model, device and methods using alternate current

Abstract

Described is a method of modulating neuronal network activities, the method including applying an alternating electric field (EF) to a neuronal network of neuronal cells in culture for a period of time, and increasing or decreasing a frequency of the alternating EF after the period of time to provide the neuronal network activities that are synchronizing or desynchronizing the neuronal network of neuronal cells in the culture, wherein increasing the frequency of the alternating electric field provides synchronizing neuronal network activities, and wherein decreasing the frequency of the alternating electric field provides desynchronizing neuronal network activities.

1 . A method of modulating neuronal network activities comprising
 applying an alternating electric field (EF) to a neuronal network of neuronal cells in culture for a period of time, and   increasing or decreasing a frequency of the alternating EF after the period of time to provide the neuronal network activities that are synchronizing or desynchronizing the neuronal network of neuronal cells in the culture,   wherein increasing the frequency of the alternating electric field provides synchronizing neuronal network activities, and   wherein decreasing the frequency of the alternating electric field provides desynchronizing neuronal network activities.   
     
     
         2 . The method of  claim 1 , wherein the EF is applied by increasing the frequency from about 0.2 Hz to about 200 kHz, wherein the EF is applied by decreasing the frequency from 200 kHz to 0.2 Hz. 
     
     
         3 . The method of  claim 1 , wherein the neuronal network activities simulate normal brain functions. 
     
     
         4 . The method of  claim 1 , wherein the neuronal network activities simulate neurological disorders. 
     
     
         5 . The method of  claim 3 , wherein the neurological disorder is Alzheimer's, Parkinson's, stroke, spinal cord injury or schizophrenia. 
     
     
         6 . The method of  claim 1  wherein the culture comprises an electrode or electrode array-embedded substrate. 
     
     
         7 . The method of  claim 1 , wherein the neuronal cells are cortical neuron, medulla neuron, inner neuron, spinal cord neuron or a combination thereof. 
     
     
         8 . The method of  claim 1 , wherein the neuronal cells were cultured for about 1-3 weeks before the EF was applied. 
     
     
         9 . The method of  claim 1 , wherein the neuronal cells comprise functional neuronal cells, wherein the functional neuronal cells are evaluated by electron microscopy, physiological measurement, electric impulse, electric potential, neuronal connectivity or neuronal marker. 
     
     
         10 . The method of  claim 9 , wherein the functional neuronal cells are alive for about 12-24 hours, about 1-2 days, about 2-4 days, about 4-7 days, about 1-2 weeks or about 2-4 weeks after the EF was applied to the culture. 
     
     
         11 . The method of  claim 1 , wherein the EF is biphasic wave or rectangular wave. 
     
     
         12 . The method of  claim 1 , further comprising: (ii) measuring the activities of the neuronal network; and (iii) detecting neuronal communities of similar activity patterns. 
     
     
         13 . The method of  claim 1 , wherein the neuronal cells are obtained from a subject with a disorder. 
     
     
         14 . The method of  claim 1 , wherein the neuronal cells are obtained from a subject that is a fetus or an infant. 
     
     
         15 . An apparatus comprising a 3D culture the 3D culture comprising
 a scaffold,   a gel region adjacent to the scaffold,   electrode pair at the interface of the scaffold and the gel region, wherein the electrode pair is spaced at least about 2 mm apart and spans a length of the interface, and   a neuronal cell comprising a neuronal cell body, an axon, and neurites, wherein the neuronal cell body is immobilized on the scaffold and the axon and neurites have free movement and growth in the gel region,   applying an alternating field electrical signal to the gel region in the 3D culture for a period of time to stimulate directed growth of the neuronal axon,   wherein the alternating field electric signal is applied with the electrode pair spaced at least about 2 mm apart, and wherein the alternating field electric signal spans gel region.