Society for Neuroscience Abstracts 28 (1998)


Neuromodulation of Synaptic Plasticity in a Reconstructed Hippocampal CA3 Pyramidal Cell Model

Elliot D. Menschik1,2 and Leif H. Finkel2,3

1Medical Scientist Training Program
2Institute of Neurological Sciences
3Department of Bioengineering

3320 Smith Walk, 301 Hayden Hall
University of Pennsylvania
Philadelphia, PA 19104, U. S. A.

menschik@neuroengineering.upenn.edu
 leif@neuroengineering.upenn.edu

Abstract

We investigate the effects of neuromodulation on synaptic plasticity in a realistic CA3 pyramidal cell model. The study was performed using GENESIS-based simulations of an anatomically reconstructed CA3 pyramidal cell (an extension of Migliore et al. 1995, J Neurophys 73:1157-1168) that included dendritic spines, a wide array of ion channels (Na, KDR, KC, KA, KM, KAHP, CaL, CaN, CaT), calcium diffusion, buffering and pumping, and AMPA- and NMDA-mediated synaptic currents. Presynaptic activity was transduced by NMDA receptor-mediated calcium influx into the dendritic spines and this signal was sequestered from shafts by a narrow spine neck and calcium pumps. Postsynaptic activity modulates dendritic calcium levels as backpropagating bursts activate voltage-gated calcium channels along the dendrite. Synaptic modification was a function of these separate calcium pools with a sliding threshold between LTP and LTD as a nonlinear function of the past history of cell firing similar to the "BCM" model (Bienenstock et al. 1982, J Neurosci 2:32-48). We demonstrate that this scheme gives rise to both LTP and LTD depending on the frequency of synaptic stimulation and show how synaptic plasticity can be regulated by acetylcholine, norepinephrine and serotonin. In particular, our results suggest that a neuromodulator-induced change from regular spiking to bursting behavior, as well as modulation of calcium channel conductances, directly alter dendritic calcium dynamics and indirectly regulate synaptic modification. (Supported by NSF-CRI and the Whitaker Foundation)

Poster S-30
Learning and Memory: Physiology -- Hippocampal II
Program number 758.19
Wednesday, 11 November 1998, 1pm
28th Annual Meeting of the Society for Neuroscience '98
Los Angeles, California November 7-12, 1998