Nitrergic Control of Corticothalamic Feedback: Implications for Absence Epilepsy.
Abstract number :
1.007
Submission category :
Year :
2001
Submission ID :
3075
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
N.C. Kurukulasuriya, M.S., Neuroscience Program/Neurobiology/Anatomy, Wake Forest Sch: Medicine, Winston-Salem, NC; W.B. Carden, PhD, Neurobiology/Anatomy, Wake Forest Sch: Medicine, Winston-Salem, NC; C.A. O[ssquote]Donovan, MD, Neurology, Wake Forest Sc
RATIONALE: Models of absence epilepsy suggest that corticothalamic synaptic transmission may cooperate with the intrinsic membrane properties of thalamic cells to generate the characteristic 3-4Hz absence rhythm. Corticothalamic feedback controls the degree and extent of both normal and pathological forms of synchronization observed in thalamocortical networks. Increased cortical feedback has been shown to switch thalamic oscillations from normal to paroxysmal (Blumenfeld and McCormick, 2000; J.Neurosci, 20(13):5153-5162). Cortical feedback onto thalamic cells is glutamatergic and mediated via NMDA and AMPA receptor systems. NMDA receptor-dependent hyperexcitability is synonymous with multiple forms of epilepsy (e.g., temporal lobe epilepsy); however, the extent of NMDA receptor involvement in absence epilepsy remains uncertain. Our interest lies in how the nitrergic projection from the parabrachial region (PBR) of the brain stem modulates NMDA receptor mediated corticothalamic feedback.
METHODS: We used an in vitro ferret slice preparation to elicit NMDA and AMPA receptor mediated excitatory postsynaptic potentials (EPSPs) in the thalamus by electrically stimulating corticothalamic fibers. We mimicked NO release from PBR terminals by treatment with nitric oxide (NO) donors.
RESULTS: We found that NO enhances corticothalamic EPSPs, particularly via selective enhancement of the NMDA receptor-mediated component. Measuring the EPSP amplitude at a time period coincident with the NMDA receptor component, we found a 89% (n=6) increse in overall EPSP amplitude, which in some cases increased the postsynaptic excitability of the relay neuron by causing subthreshold EPSPs to elicit postsynaptic spikes (n=3).
CONCLUSIONS: This finding provides the first evidence of a PBR-mediated mechanism for modulation of cortical feedback via NO. This enhancement of cortical feedback might strengthen the degree of synchronization observed at the level of the thalamus, and may factor into mechanisms underlying absence seizure occurence during the waking state.
Support: NIH RO1: EY11695.