Rebound spiking in layer II medial entorhinal cortex stellate cells: Possible mechanism of grid cell function

Abstract

Rebound spiking properties of medial entorhinal cortex (mEC) stellate cells induced by inhibition may underlie their functional properties in awake behaving rats, including the temporal phase separation of distinct grid cells and differences in grid cell firing properties. We investigated rebound spiking properties using whole cell patch recording in entorhinal slices, holding cells near spiking threshold and delivering sinusoidal inputs, superimposed with realistic inhibitory synaptic inputs to test the capacity of cells to selectively respond to specific phases of inhibitory input. Stellate cells showed a specific phase range of hyperpolarizing inputs that elicited spiking, but non-stellate cells did not show phase specificity. In both cell types, the phase range of spiking output occurred between the peak and subsequent descending zero crossing of the sinusoid. The phases of inhibitory inputs that induced spikes shifted earlier as the baseline sinusoid frequency increased, while spiking output shifted to later phases. Increases in magnitude of the inhibitory inputs shifted the spiking output to earlier phases. Pharmacological blockade of h-current abolished the phase selectivity of hyperpolarizing inputs eliciting spikes. A network computational model using cells possessing similar rebound properties as found in vitro produces spatially periodic firing properties resembling grid cell firing when a simulated animal moves along a linear track. These results suggest that the ability of mEC stellate cells to fire rebound spikes in response to a specific range of phases of inhibition could support complex attractor dynamics that provide completion and separation to maintain spiking activity of specific grid cell populations.

Reconciling the different faces of hippocampal theta: The role of theta oscillations in cognitive, emotional and innate behaviors

“…This model is also supported by some aspects of intracellular physiological data, including the difference in the frequency of resonance and subthreshold membrane potential oscillations for entorhinal neurons at different anatomical positions that has been extensively replicated (Boehlen et al, 2010;Dodson et al, 2011;Giocomo and Hasselmo, 2008a;Giocomo and Hasselmo, 2008b;Giocomo and Hasselmo, 2009;Heys et al, 2010;Pastoll et al, 2012;Shay et al, 2012). Resonance correlates with the time course of rebound from hyperpolarization, and rebound spiking might contribute to grid cell firing Shay et al, 2016).…”

Theta oscillations gate the transmission of reliable sequences in the medial entorhinal cortex

“…Stellate cells show subthreshold membrane potential oscillations and generate rebound spikes when released from inhibition 21 (Figure 1a). We modeled these properties using a hyperpolarization activated depolarizing current (Ih) 22,23 and an amplifying persistent sodium current (I NaP ) 24 in addition to leak and spiking currents (I L , I Na and I K ). We modeled interneurons using modified sodium and potassium currents that allowed it to spike at high frequency 20 .…”

Rebound spiking properties of mouse medial entorhinal cortex neurons in vivo

“…Because of the predominance of inhibitory network interactions within layer II of the MEC (Dhillon & Jones, ; Couey et al ., ) and the h‐current present in stellate cells (Dickson et al ., ; Heys et al ., ; Heys & Hasselmo, ; Tsuno et al ., ), it was proposed that inhibition enhances the excitation and firing of entorhinal neurons in a timely manner via rebound spikes (Hasselmo, ; Shay et al ., ). This possibility is supported by the current study of hyperpolarizing current stimulation with sinusoidal input in vivo .…”

“…The relationship between the amplitude or duration of hyperpolarizing current stimulation and the temporal delay of rebound spikes after stimulation has been described in in vitro recordings of MEC neurons (Ferrante et al ., ), suggesting a possible mechanism for regulating rebound spike timing by running speed. Recent studies also suggest that there is a relationship between the oscillation phase of hyperpolarizing current stimulation and subsequent spike probabilities at the peak of the oscillation in MEC layer II stellate cells in in vitro slice preparations (Shay et al ., ), suggesting a mechanism for phase precession and for maintaining select subpopulations of neurons active due to inhibition occurring at a specific phase of theta rhythm oscillations.…”