FUNCTION OF GROUP II mGluRs IN NEOCORTICAL PYRAMIDAL CELLS: INJURY RECAPITULATES ONTOGENY
Abstract number :
2.082
Submission category :
Year :
2003
Submission ID :
3930
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Anita E. Bandrowski, John R. Huguenard, David A. Prince Departments of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, CA
Glutamate activates metabotropic glutamate receptors (mGluRs) during high frequency extracellular stimulation, resulting in a decay of successive excitatory postsynaptic current (EPSC) amplitudes. To determine if this mGluR-mediated short-term plasticity is changed as a result of age and injury we used patch clamp techniques to record from layer V pyramidal neurons in young (P13-19), old (P32-P42), and injured (P35-P43) rat sensorimotor cortical slices.
We used standard patch clamp techniques to record from layer V pyramidal neurons in young (P13-19), old (P32-P42), and injured (P35-P43) of rat sensorimotor cortical slices. Injured slices were obtained from partially isolated cortical islands prepared 2 weeks prior to recording. Such lesioned cortex is known to become chronically epileptogenic (Hoffman et al, 1994).
Trains of 7-10 stimuli (50Hz) evoked EPSCs that decayed to 38% of initial amplitude in young cells (n=29) and to 37% in old cells (n=21). The decay in EPSC amplitude was significantly greater in injured cells (22%; n=29) than in either old or young cells (p[lt]0.05).
Blockade of group II mGluRs with LY341495 (2 microM) in young cells significantly reduced EPSC amplitude decay (n=10). There was also a significant reduction of EPSC decay in neurons of the undercut (n=14). No significant change occurred in old cells (n=14). Thus injury recapitulated the presynaptic modulation of glutamate release by group II mGluRs found during early development
In young cells, the effect of LY341495 was enhanced by GABA receptor antagonists gabazine (10 microM) or CGP55845 (1 microM), so that stimulus trains elicited epileptiform activity in the presence of both GABA and mGluR antagonists. In old cells, gabazine unmasked a small effect of LY341495, but did not cause epileptiform discharge.
Thus, activation of group II mGluRs provides a negative feedback on EPSCs and acts as an intrinsic antiepileptogenic mechanism in young, but not in more mature cortex. This effect reappears after injury. These data also suggest that GABA and group II mGluR mechanisms act in concert to prevent epileptiform activity in immature neocortex.
[Supported by: NIH Grants #NS12151 and #NS07280 from the NINDS, and the Pimley Research and Training Funds.]