Implantable living electrodes and methods for use thereof

Abstract

In one aspect, the invention comprises an implantable living electrode comprising a substantially cylindrical extracellular matrix core; one or more neurons implanted along or within the substantially cylindrical extracellular matrix core, the one or more neurons including one or more optogenetic or magnetogenetic neurons proximal to a first end of the implantable living electrode.

1 . An implantable living electrode comprising:
 a substantially cylindrical extracellular matrix core;   one or more neurons implanted along or within the substantially cylindrical extracellular matrix core, the one or more neurons including one or more optogenetic or magnetogenetic neurons proximal to a first end of the implantable living electrode.   
     
     
         2 . The implantable living electrode of  claim 1 , wherein the implantable living electrode is capable of bidirectional stimulation and bidirectional recording. 
     
     
         3 . The implantable living electrode of  claim 1 , wherein the implantable living electrode is capable of unidirectional stimulation and unidirectional recording. 
     
     
         4 . The implantable living electrode of  claim 1 , wherein the implantable living electrode is capable of unidirectional stimulation and bidirectional recording. 
     
     
         5 . The implantable living electrode of  claim 1 , wherein the neurons are stimulated and recorded using different wavelengths of light. 
     
     
         6 .- 9 . (canceled) 
     
     
         10 . The implantable living electrode of  claim 1 , wherein the one or more neurons include a plurality different phenotypes that target a plurality of targets and a plurality of different optogenetic or magnetogenetic phenotypes for responding to or emitting distinct wavelengths of light. 
     
     
         11 . The implantable living electrode of  claim 1 , wherein the one or more neurons include one or more selected from the group consisting of: primary cerebral cortical neurons, dorsal root ganglion neurons, glutamatergic neurons, GABAergic neurons, cholinergic neurons, dopaminergic neurons, serotonergic neurons, peptidergic neurons, neurons from the thalamus, neurons from the striatum, neurons from the hippocampus, neurons from the substantia nigra, neurons from the peripheral nervous system, and spinal motor neurons. 
     
     
         12 . The implantable living electrode of  claim 11 , wherein the primary cerebral cortical neurons include one or more selected from the group consisting of: neurons from layer I of the cortex, neurons from layer II of the cortex, neurons from layer III of the cortex, neurons from layer IV of the cortex, neurons from layer V of the cortex, neurons from layer VI of the cortex, neurons from the visual cortex, neurons from the motor cortex, neurons from the sensory cortex, and neurons from the entorhinal cortex. 
     
     
         13 . The implantable living electrode of  claim 1 , further comprising:
 one or more non-neuronal cells selected from the group consisting of: endothelial cells, myocytes, myoblasts, astrocytes, olfactory ensheathing cells, oligodendrocytes, or Schwann cells.   
     
     
         14 . The implantable living electrode of  claim 1 , wherein the neurons are derived from stem cells. 
     
     
         15 . The implantable living electrode of  claim 1 , wherein the neurons are derived from neuronal progenitor cells. 
     
     
         16 . The implantable living electrode of  claim 1 , wherein the hydrogel sheath comprises agarose. 
     
     
         17 . The implantable living electrode of  claim 1 , wherein the one or more neurons implanted along or within the substantially cylindrical extracellular matrix core are formed via forced cell aggregation. 
     
     
         18 . A method comprising:
 implanting one or more implantable living electrodes of  claim 1  in a subject's brain; and   placing a compatible stimulator in proximity to at least one of the one or more implantable living electrodes.   
     
     
         19 .- 33 . (canceled) 
     
     
         34 . A method comprising:
 implanting one or more implantable living electrodes of  claim 1  in a subject's brain; and   placing a compatible sensor in proximity to at least one of the one or more implantable living electrodes.   
     
     
         35 .- 37 . (canceled) 
     
     
         38 . A method comprising:
 implanting one or more implantable living electrodes of  claim 1  in a subject's brain; and   applying stimulus to the implantable living electrode to selectively excite or inhibit one or more selected from the group consisting of: glutamatergic neurons, GABAergic neurons, cholinergic neurons, serotonergic neurons, peptidergic neurons, neurons from the thalamus, neurons from the striatum, neurons from the hippocampus, neurons from the substantia nigra, neurons from the peripheral nervous system, spinal motor neurons, cerebral cortical neurons, dopaminergic neurons, and dorsal root ganglion neurons.   
     
     
         39 . (canceled) 
     
     
         40 . An implantable living electrode comprising:
 a substantially cylindrical extracellular matrix core;   a hydrogel sheath coaxially surrounding the substantially cylindrical extracellular matrix core;   one or more selected from the group consisting of: electrodes, optrodes, magnetic actuators, heating probes, cooling probes, or chemical applicators positioned between the substantially cylindrical extracellular matrix core and the hydrogel sheath; and   one or more neurons implanted along or within the substantially cylindrical extracellular matrix core.   
     
     
         41 . An implantable living electrode comprising:
 a substantially cylindrical extracellular matrix core; and   a plurality of aggregated neurons implanted along or within the substantially cylindrical extracellular matrix core.   
     
     
         42 .- 46 . (canceled) 
     
     
         47 . A method of treating Parkinson's disease in a patient, comprising implanting a living electrode according to  claim 41  into the substantia nigra of the patient. 
     
     
         48 . A method of manufacturing an implantable living electrode comprising:
 providing an extracellular matrix core; and   contacting at least one end of the extracellular matrix core with a plurality of aggregated neurons.   
     
     
         49 . (canceled) 
     
     
         50 . (canceled)