Muscarinic receptor activation enables persistent firing in pyramidal neurons from superficial layers of dorsal perirhinal cortex

Hippocampus. 2012 Jun;22(6):1392-404. doi: 10.1002/hipo.20975. Epub 2011 Sep 28.


Persistent-firing neurons in the entorhinal cortex (EC) and the lateral nucleus of the amygdala (LA) continue to discharge long after the termination of the original, spike-initiating current. An emerging theory proposes that endogenous persistent firing helps support a transient memory system. This study demonstrated that persistent-firing neurons are also prevalent in rat perirhinal cortex (PR), which lies immediately adjacent to and is reciprocally connected with EC and LA. Several characteristics of persistent-firing neurons in PR were similar to those previously reported in LA and EC. Persistent firing in PR was enabled by the application of carbachol, a nonselective cholinergic agonist, and it was induced by injecting a suprathreshold current or by stimulating suprathreshold excitatory synaptic inputs to the neuron. Once induced, persistent firing lasted for seconds to minutes. Persistent firing could always be terminated by a sufficiently large and prolonged hyperpolarizing current; it was prevented by antagonists of muscarinic cholinergic receptors (mAChRs); and it was blocked by flufenamic acid. The latter has been suggested to inhibit a Ca(2+) -activated nonspecific cation conductance (G(CAN) ) that normally furnishes the sustained depolarization during persistent firing. In many PR neurons, the discharge rate during persistent firing was a graded function of depolarizing and/or hyperpolarizing inputs. Persistent firing was not prevented by blocking fast excitatory and inhibitory synaptic transmission, demonstrating that it can be generated endogenously. We suggest that persistent-firing neurons in PR, EC, LA, and certain other brain regions may cooperate in support of a transient-memory system.

Publication types

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

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Entorhinal Cortex / cytology*
  • Entorhinal Cortex / physiology*
  • Male
  • Pyramidal Cells / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Muscarinic / metabolism*
  • Receptors, Muscarinic / physiology


  • Receptors, Muscarinic