Synaptically released and exogenous ACh activates different nicotinic receptors to enhance evoked glutamatergic transmission in the lateral geniculate nucleus.
The effects of 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 microM), choline (1 mM), or acetylcholine (ACh, 100 microM) markedly increased (>3-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 alpha6- and/or alpha3-containing nAChRs because it was blocked by 100 nM alpha-conotoxin MII, 100 nM dihydro-beta-erythroidine (DHbetaE), and 0.1-1.0 microM 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 alpha-bungarotoxin, 50 nM MLA, and a high concentration (30 microM) of DHbetaE, indicating that alpha7- and/or alpha8-containing receptors were involved. The results are consistent with a model whereby alpha6- and/or alpha3-containing nAChRs on retinal ganglion cell nerve terminals are located preferentially at cholinergic synapses, whereas alpha7- and/or alpha8-containing receptors are primarily extrasynaptic.
Department of Pharmacology and Physiology, George Washington University, School of Medicine and Health Sciences, DC 20037, USA. phmjzg@gwumc.edu
Jian-Zhong
JZ
Guo
Yingbing
Y
Liu
Eva M
EM
Sorenson
Vincent A
VA
Chiappinelli
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology*; D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002642:Chick Embryo; D020916:Conotoxins / Q000494:pharmacology; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D005071:Evoked Potentials / Q000528:radiation effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005829:Geniculate Bodies / Q000166:cytology*; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D011810:Quinoxalines / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000145:classification / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors
D002038:Bungarotoxins; D002121:Calcium Channel Blockers; D020916:Conotoxins; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018733:Nicotinic Antagonists; D011810:Quinoxalines; D011978:Receptors, Nicotinic; C054634:methyllycaconitine; D004079:Dihydro-beta-Erythroidine; D018698:Glutamic Acid; C056723:FG 9041; D015763:2-Amino-5-phosphonovalerate; D008274:Magnesium; D000109:Acetylcholine; D002118:Calcium; D000157:Aconitine; D001640:Bicuculline