New Publication – Robotic navigation to subcortical neural tissue for intracellular electrophysiology in vivo

Abstract: In vivo studies of neurophysiology using the whole cell patch-clamp technique enable exquisite access to both intracellular dynamics and cytosol of cells in the living brain but are underrepresented in deep subcortical nuclei because of fouling of the sensitive electrode tip. We have developed an autonomous method to navigate electrodes around obstacles such as blood vessels after identifying them as a source of contamination during regional pipette localization (RPL) in vivo. In mice, robotic navigation prevented fouling of the electrode tip, increasing RPL success probability 3 mm below the pial surface to 82% (n = 72/88) over traditional, linear localization (25%, n = 24/95), and resulted in high-quality thalamic whole cell recordings with average access resistance (32.0 MΩ) and resting membrane potential (−62.9 mV) similar to cortical recordings in isoflurane-anesthetized mice. Whole cell yield improved from 1% (n = 1/95) to 10% (n = 9/88) when robotic navigation was used during RPL. This method opens the door to whole cell studies in deep subcortical nuclei, including multimodal cell typing and studies of long-range circuits.

New & noteworthy: This work represents an automated method for accessing subcortical neural tissue for intracellular electrophysiology in vivo. We have implemented a novel algorithm to detect obstructions during regional pipette localization and move around them while minimizing lateral displacement within brain tissue. This approach leverages computer control of pressure, manipulator position, and impedance measurements to create a closed-loop platform for pipette navigation in vivo. This technique enables whole cell patching studies to be performed throughout the living brain.

W. A. Stoy, I. Kolb, G. L. Holst, Y. Liew, A. Pala, B. Yang, E. S. Boyden, G. B. Stanley, C. R. Forest
Journal of Neurophysiology Published 1 August 2017 Vol. 118 no. 2, 1141-1150 DOI: 10.1152/jn.00117.2017 PDF

Stanley Lab Welcomes ENGAGES Student Zaria Hardnett

The Stanley Lab is excited to welcome Zaria Hardnett, through Project ENGAGES (  Zaria will be working with the Stanley Lab this year alongside mentor Michael Bolus, getting hands-on experience conducting biological/engineering research.

Zaria is a rising senior at Benjamin E. Mays High School, enrolled in the Science and Mathematics Academy there. She is interested in biotechnology more generally and has previously  interned at a patent law office.

Recently, at the Project ENGAGES Summer Celebration, Zaria’s poster presentation took home first prize which includes an Amazon gift card! She presented preliminary work doing neural data processing in front of a group of peers, community members and family. Congratulations Zaria!

New Publication – Genetically expressed voltage sensor ArcLight for imaging large scale cortical activity in the anesthetized and awake mouse

With the recent breakthrough in genetically expressed voltage indicators (GEVIs), there has been a tremendous demand to determine the capabilities of these sensors in vivo. Novel voltage sensitive fluorescent proteins allow for direct measurement of neuron membrane potential changes through changes in fluorescence. Here, we utilized ArcLight, a recently developed GEVI, and examined the functional characteristics in the widely used mouse somatosensory whisker pathway. We measured the resulting evoked fluorescence using a widefield microscope and a CCD camera at 200 Hz, which enabled voltage recordings over the entire cortical region with high temporal resolution. We found that ArcLight produced a fluorescent response in the S1 barrel cortex during sensory stimulation at single whisker resolution. During wide-field cortical imaging, we encountered substantial hemodynamic noise that required additional post hoc processing through noise subtraction techniques. Over a period of 28 days, we found clear and consistent ArcLight fluorescence responses to a simple sensory input. Finally, we demonstrated the use of ArcLight to resolve cortical S1 sensory responses in the awake mouse. Taken together, our results demonstrate the feasibility of ArcLight as a measurement tool for mesoscopic, chronic imaging. © 2017 Society of Photo-Optical Instrumentation Engineers (SPIE) [DOI: 10.1117/1.NPh.4.3.031212]

P. Y. Borden, A. D. Ortiz, C. Waiblinger, A. J. Sederberg, A. Morrissette, C. Forest, D. Jaeger, G. B. Stanley, Genetically Expressed Voltage Sensor ArcLight for Imaging Large Scale Cortical Activity in the Anesthetized and Awake Mouse, Neurophotonics 4(3), 031212, 2017. PDF

PhD Proposal Announcement: Peter Borden

Peter Borden 
BME PhD Thesis Proposal Presentation
Date and Time:Thursday, March 2nd, 10-11am 
Location: Emory Rollins Research Center 1052 
Garrett Stanley (advisor)
Dieter Jaeger                                                 
Robert Liu                                                  
Bilal Haider
Biyu He (NYU) 

Title: The Impact of Thalamic State on Sensory Cortical Processing and Behavior

The thalamus is a central junction that processes both sensory afferent and motor efferent signals. Although many neurological disorders including Parkinson’s disease, Schizophrenia, and Central Pain are linked to thalamic dysfunction, basic information about thalamic processing is still unknown. Specifically, it is unclear how ongoing changes in membrane polarization (i.e. state) alter the transmission of information to and from cortical regions. Thalamic neurons have dynamic firing modes (i.e. tonic and burst) and receive tremendous amounts of neuromodulatory inputs that shape the encoding of sensory features. My project will develop novel techniques to measure entire cortical regions and use these tools determine the role of thalamic state on tactile processing and detectability of sensory inputs. Specifically, I utilize the novel genetically expressed voltage indicator ArcLight to measure voltage activity across cortical structures. I will record cortical ArcLight signals while simultaneously manipulating the ongoing thalamic activity using genetically expressed light sensitive protein channels (optogenetics). I will further combine these techniques to modulate thalamic state to control the evoked cortical response and behavioral performance of mice during a tactile detection task.  It is critical that we understand how thalamic state alters information transmission to develop better treatment options for these complex neurological disorders.

Stanley Lab Welcomes New Postdoc Caleb Wright

The Stanley lab is excited to welcome our new post-doctoral researcher,  Nathaniel (Caleb) Wright!

Nathaniel received his PhD in Physics from Washington University in St. Louis.  He worked in Ralf Wessel’s lab, where he performed multi-whole-cell and local field potential recordings of visual responses in cortex.  He and his collaborators combined these recordings with network simulations to study the dynamics and mechanisms of cortical coordination across multiple spatial scales during visual processing.