טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentAriav Gal
SubjectCellular Mechanisms allowing Integration of Synaptic Inputs
within Time Scales of Single to Hundreds of
Milliseconds in CA1 Hippocampal
Pyramidal Neurons
DepartmentDepartment of Medicine
Supervisor Professor Jackie Schiller
Full Thesis textFull thesis text - English Version


Abstract

During this work we have studied the hippocampal CA1 pyramidal neurons. We tested the synaptic input summation and output firing pattern at two different time scales: one at the sub-millisecond range and the other with hundreds of millisecond range.

Here we show for the first time by using the Patch-clamp recording technique in rat hippocampal slices that fast local spikes in basal dendrites of CA1 hippocampal neurons can support coincidence detection mechanism that  serve to improve the temporal precision of neuronal output. Integration of closely spaced basal inputs initiates local dendritic spikes with fast and short Na spike followed by slower and pronged NMDA spike.  One of the major properties of this spike is significant reduction in the EPSP rise time as recorder within the soma ( 0.31?0.13 msec vs. 3.20?1.19 msec )

In turn, these fast basal spikes allow precise timing of output action potentials with sub- millisecond temporal jitter over a wide range of activation intensities and background synaptic noise.

Persistent activity - long time scale firing: In this part of the work we have studied what are the cellular mechanisms allowing CA1 pyramidal neurons to fire for tens of seconds in response to very brief (milliseconds) stimuli.

In this work we used the blind patch-clamp technique for in vivo whole-cell recordings from CA1 neurons in the intact rat brain.  The results of this work shows that cholinergic activation combined with excitatory glutamatergic stimulation in CA1 pyramidal neurons may elicit pronged excitatory plateau potential and even long lasting persistent action potential firing lasting for many seconds.

In order to investigate the effect of combined cholinergic and excitatory stimulation on persistent activity enhancement, we used stimulation of physiological pathways for both cholinergic (m.s) and excitatory response (fim /mpp pathways).  We even used odor stimulation as a physiological excitatory pathway combined with cholinergic stimulation in order to induce persistent activity.  This phenomenon was sensitive to muscarinic antagonists, emphasizing the role of the cholinergic modulation in persistent activity formation.  

One of our main findings regards the time window between the cholinergic and excitatory stimuli.  The results show that the shorter the delay between both stimuli the higher the success rate to induce prolonged response and the average response duration is extended.  The most effective time window is up to 500 msec, while delay time of 1000 msec can hardly produce response which is more prolonged than sole m.s stimulation.