Ionic Basis of on and off Persistent Activity in Layer III Lateral Entorhinal Cortical Principal Neurons

Abstract

Principal neurons in layer III of the rat lateral entorhinal cortex (LEC) generate a self-sustained plateau potential and persistent spiking following the application of a brief suprathreshold excitatory stimulus delivered in the presence of the muscarinic receptor agonist carbachol. This persistent activity can be terminated by application of a second excitatory stimulus, and these cells can be repeatedly toggled between on and off states by consecutive excitatory stimuli. However, the ionic mechanisms that underlie the production of on and off states in layer III LEC neurons are unknown but seem to involve activity-dependent conductances, since they can be initiated by trains of action potentials evoked by either depolarizing current pulses applied to the cell or by repetitive spiking induced by activation of excitatory synaptic inputs. In this study, we obtained intracellular recordings from rat layer III LEC neurons in vitro, and a series of pharmacological and ionic substitution experiments were performed to identify mechanisms involved in the induction and termination of persistent spiking. Our data indicate that initiation of the on state depends on spike-evoked calcium influx and subsequent activation of calcium-activated nonselective cationic current. Moreover, we show that termination of persistent firing in response to an excitatory stimulus can be blocked by tetraethylammonium or iberiotoxin, suggesting that the activation of calcium-activated potassium current mediated by large conductance calcium-activated K(+) (i.e., BK) channels is required to induce the off state.

Regulation of persistent activity in hippocampal mossy cells by inhibitory synaptic potentials

“…These include modulation of intracellular Ca 2+ concentration, a pathway implicated in computational models of persistent activity in entorhinal (Fransén et al , 2006 and olfactory bulb (Inoue and Strowbridge 2008) neurons, and effects on voltage-gated ion channels modulated by muscarinic receptors. In entorhinal neurons exposed to cholinergic receptor agonists, stable persistent firing modes can be disrupted both by excitatory stimuli (Tahvildari et al 2007(Tahvildari et al , 2008 and by hyperpolarizing current steps (Egorov et al 2002), suggesting that persistent firing may require relatively specific conditions, such as a narrow range of intracellular Ca 2+ concentrations (Fransén et al 2006). Both the present results in the dentate gyrus and prior work in spinal neurons (Russo et al 1998) highlight the importance of nonsubtractive forms of synaptic inhibition that mediate large functional changes through interactions with intrinsic conductances.…”

Spontaneous Bursting Activity in the Developing Entorhinal Cortex

“…Bath application of the E4CPG (200 M) did not abolish the prolonged intrinsic bursting activity of immature mEC LIII neurons (n ϭ 4). The prolonged intrinsic bursting activity in mEC LIII neurons was also observed in the presence of atropine (10 M, n ϭ 4), indicating that cholinergic muscarinic-dependent spiking (Tahvildari et al, 2008) does not underlie this phenomenon. 2؉ ] o and inhibitors of prolonged intrinsic bursts on the periodic spontaneous field activity in the developing mEC We further investigated the potential contribution of intrinsic bursting to the periodic spontaneous field events.…”

Evolution of vocal patterns: tuning hindbrain circuits during species divergence

“…Outward currents could contribute to call period and duration by terminating depolarization in FTNs. Candidates include: calciumdependent potassium currents (El Manira et al, 1994;Cazalets et al, 1999;Del Negro et al, 1999;Tahvildari et al, 2008) Koizumi et al, 2016).…”