[Abstract Title]. - Society for Neuroscience

240. Intrinsic Membrane Properties: Modulation of Neuronal Firing Properties by Inputs
and Activity
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 240.12/E34
Topic: B.10.c. Activity-dependent plasticity of intrinsic membrane properties
Support: Clarke Foundation
Title: Molecular mechanisms of DCS induced changes in hippocampal neuron excitability
Authors: *E. DONZIS, L. WILLMOT, L. T. THOMPSON;
Behavioral & Brain Sci., Univ. of Texas at Dallas, Richardson, TX
Abstract: Aging is associated with specific deficits in hippocampal-dependent learning tasks
including trace eyeblink conditioning, spatial maze learning, and rule learning of odor
discriminations tasks. Age-related impairments have been linked to decreases in the intrinsic
excitability of hippocampal pyramidal neurons as reflected by increase amplitudes of postburst
afterhyperpolarizations (AHPs) and increases in spike-frequency adaptation (accommodation).
Slow learning young subjects also show larger AHPs and greater accommodation when
compared to naive and especially to faster learning subjects. In rats, dose-response studies have
shown that administration of 6 mg/kg of a partial NR1 agonist, D-cycloserine (DCS), improves
acquisition on spatial memory tasks and increases intrinsic neuronal excitability. The exact
mechanisms of DCS modulation of neuronal excitability are not fully understood, although
calcium-signalling pathways are implicated. A possible molecular mechanism could be through
activation of the phosphatidylinositol-3-kinase (PI3K)/Akt pathway. Many components of this
pathway have been shown to be involved in learning and memory, and activation of NMDA
receptors has been linked to activation of the PI3K pathway.
In these studies, we gave either a single injection of 6 mg/kg of DCS or a series of daily
injections over one week to FBNF-1/HSD rats and sacrificed them at varying intervals afterward.
Changes in phosphorylation of Akt in the hippocampus were examined by western blot and
changes in hippocampal intrinsic excitability were examined by sharp electrode recording from
ventral brain slices. Tissue from rats given DCS injections showed higher levels of phospho-Akt
compared to saline injected rats after a single dose when sacrificed 1 hr post-injection. DCS
injected rats also showed increases in excitability in the CA1 at the same time interval which
correlated with increases in phosphorylation of Akt. Together, these findings suggest that DCS
induces a temporally constrained increase in hippocampal pyramidal cell excitability through
activation of the PI3K/Akt pathway.
Disclosures: E. Donzis , None; L. Willmot, None; L.T. Thompson, None.