title: Electrical and Optical Activation of Mesoscale Neural Circuits with Implications for Coding.
abstract: Artificial activation of neural circuitry through electrical microstimulation and optogenetic techniques is important for both scientific discovery of circuit function and for engineered approaches to alleviate various disorders of the nervous system. However, evidence suggests that neural activity generated by artificial stimuli differs dramatically from normal circuit function, in terms of both the local neuronal population activity at the site of activation and the propagation to downstream brain structures. The precise nature of these differences and the implications for information processing remain unknown. Here, we used voltage-sensitive dye imaging of primary somatosensory cortex in the anesthetized rat in response to deflections of the facial vibrissae and electrical or optogenetic stimulation of thalamic neurons that project directly to the somatosensory cortex. Although the different inputs produced responses that were similar in terms of the average cortical activation, the variability of the cortical response was strikingly different for artificial versus sensory inputs. Furthermore, electrical microstimulation resulted in highly unnatural spatial activation of cortex, whereas optical input resulted in spatial cortical activation that was similar to that induced by sensory inputs. A thalamocortical network model suggested that observed differences could be explained by differences in the way in which artificial and natural inputs modulate the magnitude and synchrony of population activity. Finally, the variability structure in the response for each case strongly influenced the optimal inputs for driving the pathway from the perspective of an ideal observer of cortical activation when considered in the context of information transmission.
  
  
  CONCLUSIONS
  Artificial activation of neural circuitry through electrical microstimulation and optogenetic techniques is important for both scientific discovery and clinical translation. However, neural activity generated by these artificial means differs dramatically from normal circuit function, both locally and in the propagation to downstream brain structures. The precise nature of these differences and the implications for information processing remain unknown. The significance of this work is in quantifying the differences, elucidating likely mechanisms underlying the differences, and determining the implications for information processing.
authors.affiliation: Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332, and.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Millard
authors.affiliation: Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332, and.
authors.forename: Clarissa J
authors.identifier: http://orcid.org/0000-0001-5789-4293
authors.initials: CJ
authors.lastname: Whitmire
authors.affiliation: Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332, and.
authors.forename: Clare A
authors.identifier: http://orcid.org/0000-0002-7481-3552
authors.initials: CA
authors.lastname: Gollnick
authors.affiliation: School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Rozell
authors.affiliation: Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332, and garrett.stanley@bme.gatech.edu.
authors.forename: Garrett B
authors.identifier: http://orcid.org/0000-0003-2039-7706
authors.initials: GB
authors.lastname: Stanley
mesh_terms: D000818:Animals; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D009415:Nerve Net / Q000502:physiology*; D016571:Neural Networks, Computer; D062308:Optogenetics / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013003:Somatosensory Cortex / Q000502:physiology*; D013788:Thalamus / Q000502:physiology*; D014738:Vibrissae / Q000502:physiology*
keywords: VSD; coding; optogenetics; stimulation; tactile; vibrissa