Synaptically Released and Exogenous ACh Activates Different Nicotinic Receptors to Enhance Evoked Glutamatergic Transmission in the Lateral Geniculate Nucleus

Abstract

activation of nicotinic acetylcholine receptors (nAChRs) on glutamatergic transmission in the ventral lateral geniculate nucleus (LGNv) were examined in chick brain slices. Whole cell recordings showed that monosynaptic postsynaptic currents (PSCs) evoked in LGNv neurons by optic tract stimulation were blocked by glutamate receptor antagonists. Exogenously applied nicotine (0.5 M), choline (1 mM), or acetylcholine (ACh, 100 M) markedly increased (Ͼ3-fold) these evoked PSCs. Potentiation by ACh was dose-dependent and did not desensitize during a 5-min application. In a second set of experiments, the effect of releasing endogenous ACh by stimulating the lateral portion of the LGNv through a separate conditioning electrode before optic tract stimulation was examined. Conditioning stimulation trains increased PSCs by an average of 5.2-fold, an effect dependent on both the intensity and number of conditioning pulses. This increase in PSC amplitude was most likely caused by released ACh activating ␣6-and/or ␣3-containing nAChRs because it was blocked by 100 nM ␣-conotoxin MII, 100 nM dihydro-␤-erythroidine (DH␤E), and 0.1-1.0 M methyllycaconitine (MLA). In contrast, exogenously applied ACh increased PSC amplitude by activating a pharmacologically different population of nAChRs because this effect was inhibited by 100 nM ␣-bungarotoxin, 50 nM MLA, and a high concentration (30 M) of DH␤E, indicating that ␣7-and/or ␣8-containing receptors were involved. The results are consistent with a model whereby ␣6-and/or ␣3-containing nAChRs on retinal ganglion cell nerve terminals are located preferentially at cholinergic synapses, whereas ␣7-and/or ␣8-containing receptors are primarily extrasynaptic.

Temporal neurotransmitter conditioning restores the functional activity of adult spinal cord neurons in long-term culture

“…Synaptically released glutamate, serotonin, acetylcholine and other neurotransmitters have been studied in detail (Webster, 2001). However, very little in vivo information has been available about the origin and function of the pool of glutamate (Baker et al, 2002;Timmerman and Westerink, 1997), serotonin (Adell et al, 2002), acetylcholine (David and Pitman, 1982;Descarries et al, 1997;Guo et al, 2005) and other neurotransmitters which appear to be present in micromolar concentrations in the extracellular space outside the synaptic cleft (Nyitrai et al, 2006). Our results support one hypothesis in that extracellular neurotransmitters may be involved in shaping synaptic activity in vivo (Baker et al, 2002;Timmerman and Westerink, 1997;Coggan et al, 2005).…”

Cholinergic modulation of non-N-methyl-d-aspartic acid glutamatergic transmission in the chick ventral lateral geniculate nucleus

“…Throughout this study, all bath solutions contained 10 μM bicuculline to block GABA A receptor-mediated responses and 50 μM AP5 to block NMDA receptors. Previous work demonstrated that >95% of the optic tract-evoked glutamatergic response under these conditions was mediated by non-NMDA receptors (Guo et al, 2005). Bath application of ACh (100 μM for 2 min) had a biphasic effect on optic tract-evoked PSCs.…”

“…Because the optic tract is well-delineated in fresh brain slices, it is possible to selectively stimulate the retinal ganglion cell axons. Optic tract stimulation elicits monosynaptic glutamatergic PSCs in LGNv principal neurons that are mediated almost entirely by non-NMDA receptors, and these evoked responses are increased by exogenous nicotinic agonists (Guo et al, 2005). There is also more direct evidence that the cholinergic fibers within the LGNv modulate retinogeniculate transmission.…”

“…There is also more direct evidence that the cholinergic fibers within the LGNv modulate retinogeniculate transmission. Electrical stimulation of the lateral portion of the LGNv prior to optic-tract stimulation results in a marked enhancement of optic tract-evoked glutamatergic PSCs recorded in principal LGNv neurons (Guo et al, 2005). This enhanced response is completely blocked by nicotinic antagonists, demonstrating that it is due to the stimulated release of endogenous ACh from cholinergic fibers in the LGNv activating nicotinic receptors.…”

“…This enhanced response is completely blocked by nicotinic antagonists, demonstrating that it is due to the stimulated release of endogenous ACh from cholinergic fibers in the LGNv activating nicotinic receptors. Since neither ACh nor nicotine have any effect on postsynaptic responses to exogenously applied glutamate, the nicotinic receptors mediating enhanced neurotransmission in the LGNv appear to be located on the presynaptic nerve terminals of the retinal ganglion cells (Guo et al, 2005). In these previous functional studies, 1 μM atropine was present throughout the experiments to prevent activation of muscarinic receptors.…”