Ph.D Thesis

Ph.D StudentJacobson Eyal
SubjectAdaptation in Neurons and Networks of a Rat Cortex
DepartmentDepartment of Medicine
Supervisor PROF. Shimon Marom


Adaptation is one of the basic properties of excitable systems found in all levels of organization, from the molecular to the behavioral. The nervous system is constantly challenged by stimuli, so adaptation must play a key role in defining the neural activity and thus its understanding is crucial for the understanding of the nervous system. The adaptation is usually described in the literature as a monotonic process with a characteristic, usually short, time scale in both the cellular and the network level. The main goal of this work was to uncover the existence of complex, non-monotonic adaptation processes, in these levels of organization. 

I used the primary tissue culture derived from rat cortical cells. I performed intracellular recordings using the perforated cell technique and network recordings using multisite extracellular recordings from a microelectrode array.  

The spontaneous activity of the network comprises mainly of synchronized activity of most of the cells. This network activity can also be evoked by external stimuli. During repetitive low frequency stimulation, the amplitude and the timing of the response adapts in a monotonic manner. When stimulated in higher frequencies, a complex, non-monotonic, adaptation appears in which the network response switches between periods of response and periods of no response. 

I checked whether this complex adaptation is already found in the level of the single nerve cell using intracellular stimulation and recording from pharmacologically isolated cells in similar cultures. The neurons expressed a non-monotonic and complex adaptation to repetitive stimuli: when exposed to series of stimuli of higher and higher frequencies the neuron response switched between unique patterns of activation. I also exposed isolated cells to different durations of high frequency stimulation and then check the kinetics of refractoriness by low frequency stimulation. Using this paradigm, I found that the refractoriness of some of the cells is activity dependent: the longer the conditioning stimulus, the slower the recovery rate.

I used a logistic mathematical model and demonstrated that the combining of excitation and inhibition promotes the ability of the network to respond in a rich, non-monotonic pattern. Going back to the culture, I examined the effect of abolishing the activity of the inhibitory sub-network by using Bicuculline - a specific inhibitory synapse blocker. After Bicuculline application the complex, non-monotonic response disappears and replaced by a simple, monotonic, response pattern.