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.

Stanley Lab Welcomes Linlin (Mia) Lu from PKU

The Stanley lab is happy to welcome visiting graduate student Linlin (Mia ) Lu from Peking University as part of the GT /PKU partnership.

Originally from China, Linlin Lu (Mia ), is a third year postgraduate student in the PKU-GT-Emory joint BME program. She received her bachelor’s degree of engineering in the department of Biomedical Engineering in Peking University in 2014 and continued her graduate studies in the laboratory of Prof. Duan Xiaojie at  PKU. In the Duan lab, she focuses on developing flexible, soft and MRI compatible probes for chronic neural interface. As part of the Stanley lab she hopes to test the chronic recording capability and MRI compatibility of the probe in the whisker pathway, and try to combine the probe with other techniques, such as optogenetics and two-photon imaging, to develop better tools for use in neural science.


New Research Article – Thalamic state control of cortical paired-pulse dynamics

In this research article, Whitmire and colleagues have been able to utilize optogenetic modulation of thalamic firing modes combined with optical imaging of cortex in the rat vibrissa system to directly test the role of thalamic state in shaping cortical response properties.
Sensory stimulation drives complex interactions across neural circuits as information is encoded and then transmitted from one brain region to the next. In the highly interconnected thalamocortical circuit, these complex interactions elicit repeatable neural dynamics in response to temporal patterns of stimuli that provide insight into the circuit properties that generated them. Here, using a combination of in-vivo voltage sensitive dye (VSD) imaging of cortex, single unit recording in thalamus, and optogenetics to manipulate thalamic state in the rodent vibrissa pathway, we probed the thalamocortical circuit with simple temporal patterns of stimuli delivered either to the whiskers on the face (sensory stimulation) or to the thalamus directly via electrical or optogenetic inputs (artificial stimulation). VSD imaging of cortex in response to whisker stimulation revealed classical suppressive dynamics, while artificial stimulation of thalamus produced an additional facilitation dynamic in cortex not observed with sensory stimulation. Thalamic neurons showed enhanced bursting activity in response to artificial stimulation, suggesting that bursting dynamics may underlie the facilitation mechanism we observed in cortex. To test this experimentally, we directly depolarized the thalamus using optogenetic modulation of the firing activity to shift from a burst to a tonic mode. In the optogenetically depolarized thalamic state, the cortical facilitation dynamic was completely abolished. Taken together, the results obtained here from simple probes suggest that thalamic state, and ultimately thalamic bursting, may play a key role in shaping more complex stimulus-evoked dynamics in the thalamocortical pathway.

Thalamic state control of cortical paired-pulse dynamics. Clarissa J Whitmire, Daniel C Millard, Garrett B. Stanley. PDF