Muscarinic modulation of intrinsic burst firing in rat hippocampal neurons

Eur J Neurosci. 1994 Jun 1;6(6):961-6. doi: 10.1111/j.1460-9568.1994.tb00590.x.


Intracellular recordings in rat hippocampal slices were used to examine how exogenous and endogenous cholinergic agonists modulate the firing pattern of intrinsically burst-firing pyramidal cells. About 24% of CA1 pyramidal cells generated all-or-none, high-frequency bursts of fast action potentials in response to intracellular injection of long positive current pulses. Application of carbachol (5 microM) converted burst firing in these neurons into regular trains of independent spikes. Acetylcholine (5 microM) exerted a similar effect, provided acetylcholine esterase activity was blocked with neostigmine (2 microM). Atropine (1 microM) reversed this cholinergic effect, indicating its mediation by muscarinic receptors. Cholinergic agonists also caused mild neuronal depolarization but the block of intrinsic burst firing was independent of this effect. Repetitive stimulation of cholinergic fibres in the presence of neostigmine (2 microM) evoked a slow cholinergic excitatory postsynaptic potential (EPSP) lasting about a minute. During the slow EPSP, burst firing could not be evoked by depolarizing pulses and the neurons fired in regular mode. These effects were prevented by pretreatment with atropine (1 microM). Exogenously applied cholinergic agonists and endogenously released acetylcholine also reduced spike frequency accommodation and suppressed the long-duration afterhyperpolarization in burst-firing pyramidal cells in an atropine-sensitive manner. A membrane-permeable cAMP analogue (8-bromo-cAMP; 1 microM) also reduced frequency accommodation and blocked the long-duration afterhyperpolarization, but did not affect intrinsic burst firing at all. Taken together, the data show that muscarinic receptor stimulation transforms the stereotyped, phasic response of burst-firing neurons into stimulus-graded, tonic discharge.

Publication types

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

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Acetylcholine / physiology
  • Animals
  • Atropine / pharmacology
  • Carbachol / pharmacology
  • Cholinergic Agents / pharmacology*
  • Cholinergic Fibers / drug effects
  • Cholinergic Fibers / physiology
  • Electric Stimulation
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Microelectrodes
  • Neostigmine / pharmacology
  • Neurons / drug effects
  • Neurons / physiology*
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology
  • Rats
  • Rats, Wistar


  • Cholinergic Agents
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Neostigmine
  • Atropine
  • Carbachol
  • Acetylcholine