System, method and applications involving identification of biological circuits such as neurological characteristics

Abstract

Various aspects are directed to systems and methods for assessing neural activity of a neural region having multiple subfields. In certain embodiments, a method includes evoking a cellular electrical response in at least one subfield due to neural activity in the neural region, capturing image data of the electrical response at a level sufficiently detailed in space and time to differentiate between polarization-based events of two respective portions of the subfield, and then assessing neural activity by correlating space and time information, from the captured data, for the two respective portions of the sub-field. Other more specific aspects of the invention involve different preparation and neural stimulation approaches which can vary depending on the application.

1 .- 38 . (canceled) 
     
     
         39 . A system for assessing neural activity, the system comprising:
 a stimulator configured to evoke a cellular electrical response in at least one subfield of a neural tissue in a neural region having multiple subfields by stimulating neuronal cells of the neural region that express a light-activated ion channel and/or a light-activated ion pump protein;   an imager configured to capture image data of the cellular electrical response at space and time limits of resolution that allow for differentiation between polarization-based events of two portions of the at least one subfield, wherein each of the two portions comprises a group of neurons; and   a processor configured for assessing neural activity, wherein assessing neural activity comprises correlating space and time information, from the captured image data, for the two portions of the at least one subfield to produce correlation results.   
     
     
         40 . The system according to  claim 39 , further comprising a composition comprising a nucleic acid encoding the light-activated ion channel and/or the light-activated ion pump protein. 
     
     
         41 . The system according to  claim 39 , further comprising a composition for staining the neural tissue, wherein the composition comprises at least one of: a voltage sensitive dye, and a calcium sensitive dye. 
     
     
         42 . The system according to  claim 39 , wherein the correlation results comprise a correlation between a signal strength of a stimulation profile and each pixel in the image data, and wherein the processor is further configured for:
 determining the correlation between the signal strength of the stimulation profile and each pixel in the image data;   determining a cross-correlation amplitude for each pixel based on the determined correlation;   determining a cross-correlation phase for each pixel based on the determined correlation;   identifying areas of interest as a function of a spatial location of each pixel and the determined cross-correlations; and   limiting pixel variations in the image data that are not in the identified areas of interest.   
     
     
         43 . The system according to  claim 39 , wherein the processor is further configured for: assessing target locations for a treatment that includes a physical intervention. 
     
     
         44 . The system according to  claim 39 , further comprising a computer arrangement comprising:
 the processor; and   a storage medium storing computer-executable data, wherein, when the computer-executable data is executed by the processor, the processor assesses neural activity by correlating space and time information, from the captured data, for the two portions of the at least one subfield.   
     
     
         45 . The system according to  claim 39 , wherein the processor is configured for comparing the correlation results with and without a treatment for the neural region, wherein the treatment is at least one of: a pharmacological chemical based substance, a nonchemical-based therapeutic treatment, a neural-invasive treatment, a neural-genesis treatment, and a neural-modulation treatment. 
     
     
         46 . The system according to  claim 39 , wherein the processor is configured for assessing endophenotypes for a predictive value relative to a disorder. 
     
     
         47 . The system according to  claim 39 , wherein assessing neural activity further comprises assessing a role of one or more subfields within a neural circuit. 
     
     
         48 . The system according to  claim 39 , wherein neural activity is assessed relative to a depressed state of the neural region. 
     
     
         49 . The system according to  claim 39 , wherein neural activity is assessed relative to one or more of: Alzheimer's disease, mild cognitive impairment, autism, bipolar disorder, schizophrenia, and Down Syndrome. 
     
     
         50 . The system according to  claim 39 , wherein:
 the space limit of resolution is less than a centimeter;   the time limit of resolution is less than 500 milliseconds; and   the polarization-based events involve at least one of: depolarization events and hyperpolarization events.   
     
     
         51 . The system according to  claim 39 , wherein the space limit of resolution is less than about a millimeter. 
     
     
         52 . The system according to  claim 39 , wherein the subfields include dentate gyrus (DG) and CA1 subfields of the hippocampus. 
     
     
         53 . The system according to  claim 39 , wherein the neural region is selected from the group consisting of hypothalamus, frontal cortex, entorhinal cortex, cingulate cortex, mammillary bodies, septum, bed nucleus of stria terminalis, amygdala, and accumbens. 
     
     
         54 . The system according to  claim 39 , wherein the light-activated ion channel and/or the light-activated ion pump protein is at least one of: a channel-rhodopsin (ChR2), and a halorhodopsin (NpHR). 
     
     
         55 . The system according to  claim 39 , wherein the neural tissue is a brain slice. 
     
     
         56 . The system according to  claim 39 , wherein the processor is configured for correlating an activity level of the at least one subfield from the captured image data, and providing processed correlation results useful for assessment of the response of the neural region. 
     
     
         57 . The system according to  claim 41 , wherein the composition for staining the neural tissue comprises the voltage sensitive dye. 
     
     
         58 . The system according to  claim 39 , wherein the stimulator is configured to evoke the cellular electrical response by optically stimulating the neuronal cells. 
     
     
         59 . The system according to  claim 39 , wherein the stimulator is configured to evoke the cellular electrical response by electrically stimulating the neuronal cells. 
     
     
         60 . The system according to  claim 39 , wherein the stimulator is configured to evoke the cellular electrical response by using infrared light. 
     
     
         61 . The system according to  claim 42 , wherein the processor is configured for limiting pixel variations in the image data that are not in the identified areas of interest by median filtering the image data. 
     
     
         62 . The system according to  claim 61 , wherein the processor is configured for median filtering the image data by median filtering with a 3×3 pixel window.