Abstracts

RATIONALE: The corticothalamic feedback projection from layer VI of the cerebral cortex converges onto both thalamic relay cells (TC) and thalamic reticular nucleus (TRN) cells. The degree of cortical feedback directly impacts the generation of spike wave discharges within thalamic networks. Much like those seen in TC cells, corticothalamic synapses within the TRN also contain AMPA and NMDA receptors. The object of this study was to delineate how brain nitric oxide synthase (bNOS) containing terminals from the brain stem parabrachial region (PBR), that pervade both the LGN and TRN, influence corticothalamic feedback. We have previously shown (Kurukulasuriya et al., 2001. Epilepsia 42 (7) 6) that Nitric Oxide, NO released from the PBR, enhances corticothalamic excitatory post synaptic potentials, EPSPs in the LGN. This effect was further shown to be largely mediated through a cGMP mediated NO-NMDAR interaction. Since TRN cells comprise a preferential target for corticothalamic fibers (Steriade, 2001: PNAS Vol 98 (7) 3625-3627 and Golshani et al, 2001: PNAS. Vol 98 (7) 4172-4177) the effect of NO on EPSPs within the TRN is of particular significance. We hypothesized that NO influences corticothalamic EPSPs in the TRN.
METHODS: We tested this with intracellular recordings in adult ferret ([gt]P35) TRN/LGN slices. We evoked EPSPs in the TRN via a bipolar stimulating electrode (1mA, 0.1msec pulses) placed in the optic radiations. GABAA and GABAB IPSPs were blocked with 50mM bicuculline methiodide and 200mm 2-OH-Saclofen respectively. Pharmacological agents including the NO donor S-nitroso-N-acetyl-DL (SNAP,2mM) were bath applied using a computer controlled superfusion system.
RESULTS: As with TC cells, CT EPSPs in hyperpolarized TRN cells were rapid, while a slower component appeared at depolarized potentials (n=24). Paired pulse facilitation of the CT EPSPs in the TRN was apparent (n=10). The delayed EPSP in the TRN was shorter compared to those seen in the LGN. The rapid component was DNQX (30mM) sensitive and AMPAR mediated (n=3), while the delayed component was APV (150mM) sensitive and NMDAR mediated (n=3). Application of the NO donor SNAP (2mM) selectively enhanced the NMDAR component of the TRN CT EPSP (n=5), sometimes transforming the EPSP into a burst. Voltage isolation of the AMPA component revealed that NO did not significantly alter AMPA transmission (n=6).
CONCLUSIONS: The NO mediated increase in NMDAR activity within the TRN may result in greater synaptic activation of TRN cells, which in turn could increase inhibition of TC cells, promoting rebound bursts. This finding suggests a brainstem/PBR contribution to the relative strength of corticothalamic excitatory input in the TRN. We speculate that controlling the nitrergic influence at the cortico-TRN synapse could impact the generation of thalamic spike and wave discharges.
[Supported by: EY11695.]