Artificial Synaptic Conductances Reduce Subthreshold Oscillations and Periodic Firing in Stellate Cells of the Entorhinal Cortex

Abstract

Previous work has established that stellate cells of the medial entorhinal cortex produce prominent intrinsic subthreshold oscillations in the voltage response concentrated within the theta range (3-7 Hz). It has been speculated that these oscillations play an important role in vivo in establishing network behavior both in the entorhinal cortex and hippocampus. Consequently, it is important to investigate under what conditions theta oscillations in stellate cells can be generated and whether the spike-train power spectral density (PSD) also carries power at theta. We investigated the ability of stellate cells to generate theta oscillations in the presence of generic in vivo-like patterns of stimulation. Inputs were Poisson process-driven excitatory and inhibitory synaptic conductances or currents, introduced via dynamic clamp. We analyzed the subthreshold membrane oscillations and spike-train behavior in the presence of comparable synaptic conductance-or current-mediated membrane fluctuations. In the presence of conductance-based synapses, subthreshold oscillations are highly attenuated or entirely eliminated. Conversely, with current-based synapses stellate cells retain their ability to generate subthreshold oscillations in the theta band. These results also extend into the spiking regime, where only under current-based synapses does the PSD of the spike train show a prominent peak at theta. Furthermore, the peak in the spike-train PSD and spike clustering results from an increased probability of firing after a spike afterhyperpolarization and not directly from subthreshold oscillatory dynamics as has been previously suggested. Our results suggest that subthreshold oscillations may contribute less to in vivo response properties than has been hypothesized.

Pyramidal Neurons Switch From Integrators In Vitro to Resonators Under In Vivo-Like Conditions

“…Moreover, these results are consistent with reported effects of acetylcholine on low-frequency oscillations during slow-wave sleep (Steriade 2004). At first glance, our results appear to contradict Fernandez and White (2008), who showed that MPOs in entorhinal stellate cells were strongly attenuated by increased membrane conductance; in fact, our results are consistent insofar as shunting also attenuated MPOs in CA1 pyramidal cells and abolished spiking associated with those MPOs (see Fig. 7A).…”

Conditional Bursting Enhances Resonant Firing in Neocortical Layer 2–3 Pyramidal Neurons

“…In stellate cells of the entorhinal cortex, increasing conductance by dynamic clamp reduced subthreshold theta oscillations and spike clustering at theta frequency caused by the mAHP (Fernandez and White, 2008). Based on this and a possible reduction of bursting, we expect that the primary resonance of L2-3 PNs will be smaller in high-conductance states.…”

Development of Theta Rhythmicity in Entorhinal Stellate Cells of the Juvenile Rat

“…The falling magnitude of the impedance at low frequencies and the increasing bandwidth indicate that resistance is lower at P28ϩ than that at P14. Yet, artificially decreasing resistance in stellate cells (P19 -P31) has been shown to lower resonance and both MPO amplitude and theta content (Fernandez and White 2008). Thus there must be a strong current contributing to resonance for impedance to become more resonant from P14 to P18.…”

“…An overshooting (underdamped) response to a perturbation is a property of any resonant system and in EC layer II stellate cells the robust rebound and overshoot of the AHP have been shown to be essential for spike clustering (Fernandez and White 2008;Nolan et al 2007). We may therefore characterize development between P14 and P18 as being one of increasing resonance.…”