Nicotinic excitatory postsynaptic potentials in hippocampal CA1 interneurons are predominantly mediated by nicotinic receptors that contain α4 and β2 subunits

Neuropharmacology. 2011 Dec;61(8):1379-88. doi: 10.1016/j.neuropharm.2011.08.024. Epub 2011 Aug 25.


In the hippocampus, activation of nicotinic receptors that include α4 and β2 subunits (α4β2*) facilitates memory formation. α4β2* receptors may also play a role in nicotine withdrawal, and their loss may contribute to cognitive decline in aging and Alzheimer's disease (AD). However, little is known about their cellular function in the hippocampus. Therefore, using optogenetics, whole cell patch clamping and voltage-sensitive dye (VSD) imaging, we measured nicotinic excitatory postsynaptic potentials (EPSPs) in hippocampal CA1. In a subpopulation of inhibitory interneurons, release of ACh resulted in slow depolarizations (rise time constant 33.2 ± 6.5 ms, decay time constant 138.6 ± 27.2 ms) mediated by the activation of α4β2* nicotinic receptors. These interneurons had somata and dendrites located in the stratum oriens (SO) and stratum lacunosum-moleculare (SLM). Furthermore, α4β2* nicotinic EPSPs were largest in the SLM. Thus, our data suggest that nicotinic EPSPs in hippocampal CA1 interneurons are predominantly mediated by α4β2* nicotinic receptors and their activation may preferentially affect extrahippocampal inputs in SLM of hippocampal CA1.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Acetylcholine / metabolism
  • Aconitine / analogs & derivatives
  • Aconitine / pharmacology
  • Animals
  • Biophysics
  • CA1 Region, Hippocampal / cytology*
  • Channelrhodopsins
  • Cholinergic Fibers / physiology
  • Diagonal Band of Broca / drug effects
  • Diagonal Band of Broca / metabolism
  • Dihydro-beta-Erythroidine / pharmacology
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects*
  • Excitatory Postsynaptic Potentials / genetics
  • In Vitro Techniques
  • Interneurons / drug effects*
  • Light
  • Mice
  • Neural Pathways / physiology
  • Nicotine / pharmacology*
  • Nicotinic Antagonists / pharmacology
  • Optics and Photonics
  • Patch-Clamp Techniques
  • Quinoxalines / pharmacology
  • Receptors, Nicotinic / metabolism*
  • Transduction, Genetic
  • Voltage-Sensitive Dye Imaging


  • Channelrhodopsins
  • Excitatory Amino Acid Antagonists
  • Nicotinic Antagonists
  • Quinoxalines
  • Receptors, Nicotinic
  • nicotinic receptor alpha4beta2
  • methyllycaconitine
  • Dihydro-beta-Erythroidine
  • FG 9041
  • Nicotine
  • 2-Amino-5-phosphonovalerate
  • Acetylcholine
  • Aconitine