Sabbatical Project Report 2013-14
Name, Faculty Rank, Department:
Dr. Jozsi Z. Jalics, Associate Professor, Department of Mathematics and Statistics
Title of Sabbatical/FIL Project:
Localization of Single Neuron Current Sources Based on Extracellular Potentials
Abstract/Overview of Project:
My sabbatical project focused on the localization of single neuron current sources from
extracellular potentials as a Fulbright Fellow at the Wigner Research Centre for Physics
within the Hungarian Academy of Sciences in Budapest, Hungary. This collaborative
work with Zoltán Somogyvári and Dorottya Cserpán led to our development of a new
spike Current Source Density (sCSD) method for spherically shaped neurons such as
those in the thalamus, a brain region that serves as a relay center for sensory information.
This method is based on the inverse solution of the Poisson-equation. The source model
with spherical symmetry is constructed using the zeroth and first order spherical
harmonics of Laplace. The calculation of the potential field of these spherical harmonics
is done by calculating the inner and outer momentums and using the Legendre
polynomials. Inverting the calculated field and completing the algorithm with a cellelectrode distance estimation method, leads to our sCSD method for spherical cells. We
have successfully applied the method to thalamic data consisting of EC recordings of
awake rats from the lab of László Acsády. Relative to the traditional CSD method, our
method yields more accurate, flexible, and asymmetric results and has the advantage of
providing an approximation of the cell-electrode distance and the ability to reveal the
distribution of synaptic inputs onto the cells.
Sabbatical/FIL Results:
My sabbatical experience during the 2013-14 academic year in Budapest, Hungary
was very rewarding and fruitful. I joined the Computational Neuroscience Research
Group of the Wigner Research Centre for Physics within the Hungarian Academy of
Sciences as a Visiting Research Fellow. In addition, I applied for and received a
Fulbright Research Fellowship with a 5 month duration that was later extended an
additional 4 months. My Fulbright award was 1 of only 4 such research awards that year
in Hungary granted in all disciplines. I was an active participant in my research group,
which was housed in the Department of Theoretical Physics and consisted of more than
12 faculty, postdocs, and graduate students. I shared an office with my close
collaborators, Zoltán Somogyvári and Dorottya Cserpán. Typically, we worked 4 full
days in the office, with the entire research group having lunch together, and one day at
home. The office was on the KFKI campus on the small mountain of Csillebérc on the
outskirts of Budapest, and housed a working experimental nuclear reactor. I regularly
participated in and presented at our group's seminars which were held twice a week. In
addition, group members and I often attended lectures in other departments on campus
and at other universities in Budapest including frequent lectures at the Budapest
University of Technology and Economics beside the Danube River as well as local
conferences such as the Wigner 111 Scientific Symposium in Budapest in November
2013. I also traveled with several of my colleagues to the IBRO (International Brain
Research Organization) Workshop in January 2014 and presented a poster of my research.
Furthermore, I gave an invited talk at the Eszterházy Károly College in Eger, Hungary in
November 2013.
My research focused on the localization of single neuron current sources from
extracellular potentials. (See below for a more detailed account of my research.) In
particular, we were able to develop a new spike Current Source Density (sCSD) method
for spherically shaped neurons such as those in the thalamus, a brain region that serves as
a relay center for sensory information. Relative to the traditional CSD method, our
method yields more accurate, flexible, and asymmetric results and has the advantage of
providing an approximation of the cell-electrode distance. I have written a manuscript
regarding the work entitled Single Cell Current Source Computation in the Thalamus and
gave a seminar talk about it at the Wigner Research Centre for Physics. A poster of our
research entitled Interpretation of Microelectrode Recordings with a Focus on Single
Neurons is also being presented at the 15 Biannual Conference of the Hungarian
Neuroscience Society in January 2015. In March, I will be giving an invited talk at the
U.S. Fulbright Alumni Meeting at the Hungarian Embassy in Washington DC as well
giving two talks on the work at the YSU Analysis Seminar. Our ongoing and future work
includes the generation of new results from our thalamic data, improvements to our
method, and revisions to our manuscript. We expect that our collaboration will continue
to be fruitful for many years to come. Furthermore, I developed strong bonds, which I
plan to preserve, with the entire research group. In addition to my new research project, I
also worked on a manuscript regarding cardiac electrophysiology and modeling that was
a collaboration with Mark Womble, Carl Sims, and students from YSU's MBUR program
(Joshua Mike, Zane Kalik). In January 2014, we submitted to the Journal of Cardiac
Electrophysiology our paper entitled Sex and Regional Differences in Rabbit Right
Ventricular L-Type Calcium Current Levels and Mathematical Modeling of Arrhythmia
Vulnerability. The paper is under revision currently.
My Fulbright award also led me to numerous and varied educational experiences. I
attended monthly meetings organized by the Hungarian Fulbright Commission that
included day-long excursions in Budapest or overnight trips within Hungary. My
experiences included: an excursion to the Danube bend and visitation of the medieval
castle of Visegrad (09/13), a tour of the Jewish Quarter of Budapest including the
Holocaust Memorial Center and 2 famous Jewish synagogues (11/13), a visit to the
Hungarian Parliament and a private meeting with members of Parliament (12/13), a tour
of the Hungarian Academy of Sciences (2/14), a Romani Cultural Evening (3/14), a tour
of the University of West Hungary (where my grandfather studied in the early 1900s) and
the cities of Györ and Mosonmagyarovár (4/14), a tour of the Office of the President of
the Republic in the castle district in Budapest (4/14), and a visit to the city of Eger
including its famous castle and Eszterházy Károly College (5/14). I also attended several
Fulbright seminars in Budapest and chaired the Conference of the Returned Hungarian
Fulbright Grantees in January 2014.
In addition to developing a strong collaborative relationship with my host research
group, my entire family and I participated in experiences of a lifetime and formed
valuable new networks of friends. My three children attended Hungarian Catholic
schools and our family was immersed in their school communities through frequent
spiritual and social gatherings and class and school outings. My family joined me in
most of the tours and educational experiences that really gave us a deeper understanding
of the Hungarian culture and educational system while experiencing the sights, sounds,
and flavors of Hungarian life. These tours also fostered the development of a network of
friends consisting of the current and former Fulbrighters. Finally, my sabbatical
experience allowed my family and I to explore other European cultures through trips
(mostly during the summers) to neighboring countries. In particular, my wife and I had
volunteered for a year at a Hungarian children’s home and school (St. Francis Foundation)
in Romania ten years earlier. In October 2013, we had the opportunity to attend the
Foundation’s 20th reunion and meet with numerous friends and former colleagues and
students from our time there. Then after school ended in the summer, we spent a week
traveling around the Transylvanian region of Romania and stayed at several of the
Foundation’s homes run by former colleagues and students. It was wonderful to see the
progress of the Foundation and our former students, many of whom now work for the
Foundation, and to share their amazing work with our own children. In summary, my
sabbatical experience led to a very fruitful and exciting ongoing research collaboration
while providing my family and I with eye-opening experiences of a lifetime that will
continue to shape who we are for the rest of our lives.
Reseach on Localization of Single Neuron Current Sources
An average neuron in the central nervous system receives 10-15 thousand synaptic
inputs from other neurons. While many fine details are known about the properties of
individual synapses, the spatio-temporal transmembrane current patterns, resulting from
the summation of a huge number of individual synaptic inputs on a whole neuron, are
almost entirely unknown. The main reason for this large gap in our knowledge is the lack
of a proper technique for measuring spatio-temporal input patterns on single neurons in
behaving animals. While the output of a neuron is well recognizable in the extracellular
potential measurements in the form of action potentials, the input that evoked the
observed spike is unknown. Without knowing the input, deciphering the input-output
transformation implemented by an individual neuron is impossible.
The steadily improving optical imaging techniques provide extremely good spatial
resolution, but they still have not reached the speed, signal-to-noise ratio, sampling
frequency, aperture and miniaturization properties necessary to record action potentials
and synaptic input patterns on whole neurons in behaving animals. On the other hand,
the number of channels, together with the spatial resolution, have dramatically increased
recently in the widely used multi-electrode arrays (MEA), and further improvements are
expected [1],[2],[3]. This relatively low cost technique is applicable to freely behaving
animals as well. Traditionally, only the spike timings are used from these extracellular
(EC) potential recordings, but recent improvements significantly increased the spatial
information content of these measurements and have allowed a new micro-electric
imaging technique to be developed for source reconstruction by my collaborators, the
spike current source density (sCSD) method [4].
Whereas the traditional CSD method calculates the neural current source distribution
of EC potential patterns while incorporating assumptions that make it inaccurate for
single-cell activity, the sCSD method has been specifically designed to reveal the CSD
distribution of single cells during action potential generation. This method is based on the
inverse solution of the Poisson-equation. Based on a priori knowledge of the anatomical
and biophysical properties of the cell, a parametric model of the current sources is
constructed that is simple enough to estimate the corresponding parameters, but still
provides accurate and general description of the system. In order to reconstruct the
spatio-temporal distribution of membrane currents of a single neuron, prior assumptions
about the shape of its dendritic tree and estimates of its distance from the electrodes must
be made. The sCSD method used a linear source model to approximate the complex
morphology of cortical neurons. This approximation fits well to data measured with
linear probes and to the cortical structure in many ways: It fits to the morphology of
cortical pyramidal neurons, and their arrangement, but most importantly it captures the
most informative direction of the laminar organization of the input to the cortical
neurons. However, the organization of synaptic input follows different geometry in other
brain structures, such as the thalamus or other subcortical nuclei, and requires a different
approach.
My sabbatical and ongoing work involves the modification of the sCSD method to
spherically shaped neurons such as those in the thalamus in collaboration with Zoltán
Somogyvári and Cserpán Dorottya (Hungarian Academy of Sciences). In the thalamus,
which serves as a relay center for sensory information, the different input pathways are
separated by their proximity on the dendrites. This means that away from the cortex, the
effect of different input pathways cannot be separated on a population level using the
previous method. In contrast, our single neuron sCSD approach carries the potential to
reveal the dynamics of different inputs on the thalamic relay cells. We have developed a
new sCSD method, a new model-based inverse solution, using a spherical source
structure model to reveal synaptic input distribution on thalamic relay cells. The source
model with spherical symmetry is constructed using the zeroth and first order spherical
harmonics of Laplace. The calculation of the potential field of these spherical harmonics
is done by calculating the inner and outer momentums and using the Legendre
polynomials. Inverting the calculated field and completing the algorithm with a cellelectrode distance estimation method, leads to our sCSD method for spherical cells.
We have begun to apply the method to thalamic data consisting of EC recordings of
awake rats from the lab of László Acsády. Relative to the traditional CSD method, our
method yields more flexible asymmetric results that exhibit forward and backward action
potential progagation and has the advantage of providing an approximation of the cellelectrode distance. We are continuing to test and refine the method and are using the
method to investigate additional biological questions. In particular, we would like to
investigate how the sCSD changes when the animal is stimulated in different ways
(whisker vs. flash stimulation). Also, the thalamic data includes inputs from the cortex
during cortical up and down states, and we would like to investigate how these inputs
change during the different states. Finally, we are continuing to revise our manuscript
regarding the work that is in preparation.
[1] Buzsáki G., Large-scale recording of neuronal ensembles. Nat Neurosci.
May;7(5):446-51, 2004.
[2] Kipke D.R., Shain W., Buzsaki Gy., Fetz E., Henderson M.J., Hetke J.F. and Schalk
G., Advanced Neurotechnologies for Chronic Neural Interfaces: New Horizons and
Clinical Opportunities, J Neurosci. 28(46):11830 –11838, 2008.
[3] Berényi A., Somogyvári Z., Nagy A., Roux L., Long J., Fujisawa S., Stark E.,
Leonardo A., Harris T. and Buzsáki Gy., Large-scale, high-density (up to 512 channels)
recording of local circuits in behaving animals, J. Neurophysiol., 2014.
[4] Somogyvári Z, Cserpán D., Ulbert I., Érdi P., Localization of single cell current
sources based on extracellular potentials patterns: the spike CSD method, European
Journal of Neuroscience, Volume 36, Issue 10, pages 3299–3313, 2012.
[5] Cserpán D., Jalics J., Barthó P., Acsády L., Somogyvári, Z., Interpretation of
Microelectrode Recordings with a Focus on Single Neurons, 15th Biannual Conference of
the Hungarian Neuroscience Society, Budapest, Hungary, January 2015.