טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentOri Hillel
SubjectExcitability Dynamics of Isolated Neuron at Different
Stimulation Frequencies
DepartmentDepartment of Physics
Supervisors Full Professor Braun Erez
Full Professor Marom Shimon


Abstract

Ever since the seminal work of Hodgkin and Huxley in the 1950's, the dominant paradigm in neuroscience assumes that membrane excitability is a process that may be regarded as reliable over time scales that extend beyond one second or so. In other words, the stereotypic voltage response named action potential is independent of the history of stimulation beyond couple hundreds of milliseconds. Whenever richer neuronal dynamics are observed, the tendency is to attribute them to synaptic or network-level processes that impact on (but independent of) the machinery of membrane excitability in itself. 

Recent studies have demonstrated that this assumption might be wrong. When the stimulation frequency is increased to physiological values, the neuronal responsiveness is characterized by practically scale-invariant response fluctuations, long-memory processes and transitions between quasi-stable modes of response patterns. Within the framework of current models of membrane excitability, the interpretation of these long-term dynamics is not trivial.

This study focus on one interpretation suggested, that these complex dynamics reflect residence of the system about a second order phase transition. The experiment conducted was aimed at uncovering the hallmark of second order phase transitions, that is ? divergence of relevant measures as the system approaches the critical point. For each neuron several stimulation frequencies were chosen as means to drive the system to different points proximal to the critical point, and the neuron was stimulated for one hour at each. Stimulation and recordings were performed extra-cellularly using substrate embedded electrodes, a method catering for long-lasting stable experiments.

The results of the experiment are not quite conclusive. The analysis does indicate what seems as an approach to a critical point as the stimulation rate is increased, but we were not able to demonstrate a general trend common to all, or at least most of the examined neurons. Beside dynamic features that are general for all neurons, each one also has dynamic features of its own characteristics, occasionally masking the properties we aim to uncover. Under these conditions, identifying general principles is impossible.

We believe that the inconclusive results reflect inadequacy of the experimental system in this context. The assumption that a neuron can be ‘clamped’ at a given distance from the critical point by constant-rate stimulation might be too strong. Another source of difficulty concerns the uncontrolled spatial dimension. In the substrate-embedded electrode setup used here, spatial aspects of the experiment are largely invisible and thus typically ignored.

Contemplating ways to proceed, we acknowledge that the question under research should be approached at the level of a membrane patch, calling for investigation in a reduced system. The work concludes with a description of a suggested reduced system, taking a bio-synthetic approach currently developed in our lab. It provides well defined control parameters, and control over excitability components. With this new system in hand, we expect a systematic research of the excitability dynamics in general, and the complexity phenomenon in particular - exploring phase transitions as well as other points of view - to be successful and fertile.