Neuroscience 2004 Abstract
| Presentation Number: | 931.2 |
|---|---|
| Abstract Title: | Mechanisms behind stable graded persistent spiking activity in entorhinal cortex neurons. |
| Authors: |
Fransen, E. A.*1
; Hasselmo, M. E.2
; Alonso, A. A.3
1Dept Computer Sci, Royal Inst Technol, Stockholm, Sweden 2MA, Lindstedsv 5, SE-10044, 3USA, Lindstedsv 5, SE-10044, |
| Primary Theme and Topics |
Cognition and Behavior - Human and Animal Cognition and Behavior -- Learning & memory: Physiology and imaging |
| Secondary Theme and Topics | Cognition and Behavior<br />- Human and Animal Cognition and Behavior<br />-- Learning & memory: Pharmacology |
| Session: |
931. Learning: Experiments and Models Slide |
| Presentation Time: | Wednesday, October 27, 2004 1:15 PM-1:30 PM |
| Location: | San Diego Convention Center - Room 1B |
| Keywords: | cationic current, intrinsic neuronal excitability, integrator activity, metabotropic modulation |
Recently, we have shown that in synaptically isolated pyramidal cells in entorhinal cortex layer V, repetitive application of an input can generate multiple stable graded levels of firing (Egorov et al, Nature 2002). The process depends on the stimulation of metabotropic (muscarinic, mGluR1) receptors, and the activation of a CAN current. In this work we have utilized computational modeling to elucidate possible mechanisms involved in this phenomena. We have proposed that the core mechanism is a hysteresis in the activation of kinases or phosphatases affecting the Ca-sensitivity or channel open time of the CAN-current (Fransen et al, SFN abstracts 2003). Using the model, we now study the mechanisms behind initiation of a change in level as well as the mechanisms involved in sustained activity and stability to distractors. Our simulations show that the stable graded spiking activity observed experimentally is not accomplished merely by extensive balancing of currents across an interval of voltage, as proposed by Durstewitz (2003), as that approach generically leads to slow oscillations in the activity around the stable point. Further, as available data on processes related to Ca generally show inactivation or desensitization eg of the Ca-channel itself or of the Ca-buffers, models based on tonically sustained Ca-diffusion (Loewenstein et al 2003) will not be stable when Ca-related processes inactivate/desensitize. Further, recent experiments using thapsigargin or CPA show that the stable levels do not depend on processes related to Ca-stores (Tahvidari et al, SFN abstracts 2004). Instead, a model based on shifts in the balance of kinases and phosphatases due to transient changes in Ca, as the one presented in this work, are supported.
Supported by VR 240-00023-061, CIHR MT-10914, NIH MH61492 and HFSP
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2004 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2004. Online.
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