Determinants of CA3 Burst Timing
Abstract number :
3.107
Submission category :
Translational Research-Basic Mechanisms
Year :
2006
Submission ID :
6792
Source :
www.aesnet.org
Presentation date :
12/1/2006 12:00:00 AM
Published date :
Nov 30, 2006, 06:00 AM
Authors :
1Audrey S. Yee, 2Lihong Diao, and 1,2Kevin J. Staley
The spontaneously active in-vitro CA3 slice preparation is an important model of interictal spikes. The temporal pattern of interictal spikes reflects seizure probability in experimental epilepsy. We investigated determinants of CA3 burst timing to understand mechanisms of interictal timing. In numerous paradigms used to initiate bursts, we noted a significant increase in the interburst interval in the 1st hour following burst onset. The mechanisms for this finding are unclear and we investigate them here., We used rat hippocampal slices (male Sprague-Dawley 4-8 weeks, 400uM sections prepared with a tissue chopper, slices cut and stored in ACSF) and extracellular field recordings to record bursting from the CA3 pyramidal cell layer. This bursting was induced in modified ACSF (3.3 K+, 0.9 Mg2+, 1.5 Ca2+) by addition of: (1) Pictrotoxin (PTX) 100uM + CGP 1uM (2) Bicuculline Methiodine (BMI) 50uM + CGP or (3) Gabazine (GBZ) 10uM + CGP to block GABA[sub]A[/sub] and GABA[sub]B[/sub] receptors. In other experiments, slices were co-treated with a glutamate precursor, glutamine (10uM) or pretreated with the NMDA receptor (NMDAR) antagonist, d-APV 100uM, prior to GABA[sub]A[/sub] and GABA[sub]B[/sub] blockade. Changes in burst frequency (measured as interburst interval) and burst length were examined., 1. Synchronized network activity can occur in the presence of postsynaptic inhibition.
2. Burst frequency increased during the first hour following burst initiation.
3. The initial burst frequency increase was present regardless of the type of GABA[sub]A[/sub] receptor blockade (BMI, PTX, and GBZ).
4. This initial burst frequency increase occurred in the presence of glutamine replenishment.
5. This initial burst frequency increase occurs in the presence of NMDAR blockade, suggesting that burst-related synaptic plasticity does not explain the initial increase in burst frequency.
6. When the degree of post-synaptic inhibition was increased (see concentration- response curve), initial burst frequency increase was diminished., These results suggest that inhomogeneous GABA[sub]A[/sub] receptor function is reflected in altered burst frequency in the 1st hour after burst induction. Similar inhomogeneities may be present in-vivo early in epileptogenesis., (Supported by NINDS.)
Translational Research