Facilitation of glutamatergic neurotransmission by presynaptic nicotinic acetylcholine receptors

Neuropharmacology. 2000 Oct;39(13):2715-25. doi: 10.1016/s0028-3908(00)00145-3.


The profiles of presynaptic facilitation of glutamate release as elicited by nicotine and acetylcholine were compared in two limbic pathways recapitulated in vitro. At synapses of medial habenula (MHN) and interpeduncular nucleus (IPN) neurons, application of nicotine increased the frequency of TTX-resistant, spontaneous postsynaptic currents (SSCs) by an average of 5-fold. In contrast, the average increase in SSC frequency elicited by nicotine was more than 120 fold at synapses of olfactory bulb (OB) and amygdala neurons. At both preparations, pulses of ACh caused presynaptic facilitation that lasted longer than that elicited by nicotine. The subunit composition of presynaptic nAChRs may contribute to the different profiles of facilitation observed. The large magnitude, fast kinetics, and alpha-bungarotoxin sensitivity of facilitation observed at OB-amygdala synapses is consistent with participation of alpha7-type nAChRs. As subunit-selective deletion of alpha5 or alpha7 altered the profile of nicotine-elicited facilitation at MHN-IPN synapses, presynaptic nAChRs at MHN-IPN synapses appear to be more complex. Such heteromeric combinations of nAChRs may contribute to the lower magnitude and slower kinetics of presynaptic facilitation at MHN-IPN synapses. Calcium influx through either voltage-gated calcium channels or directly through presynaptic alpha7-containing nAChRs is sufficient to support nicotine-elicited facilitation of glutamate release. Resultant increases in intracellular calcium may further modulate presynaptic nAChR activity in a subunit-composition dependent manner.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Chick Embryo
  • Electrophysiology
  • Female
  • Glutamic Acid / physiology*
  • Habenula / metabolism
  • Habenula / physiology
  • Mesencephalon / metabolism
  • Mesencephalon / physiology
  • Mice
  • Olfactory Bulb / metabolism
  • Olfactory Bulb / physiology
  • Oligonucleotides, Antisense / pharmacology
  • Pregnancy
  • Receptors, Nicotinic / metabolism
  • Receptors, Nicotinic / physiology*
  • Receptors, Presynaptic / physiology*
  • Synapses / metabolism
  • Synapses / physiology
  • Synaptic Transmission / physiology*
  • alpha7 Nicotinic Acetylcholine Receptor


  • Chrna7 protein, mouse
  • Oligonucleotides, Antisense
  • Receptors, Nicotinic
  • Receptors, Presynaptic
  • alpha7 Nicotinic Acetylcholine Receptor
  • Glutamic Acid
  • Calcium