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Oscillations, persistent spiking and grid cells

Michael E. Hasselmo and Mark P. Brandon

Center for Memory and Brain, Boston University, USA


We have used slice physiology, unit recording and computational modeling to study the role of cellular mechanisms in grid cell firing. We initially tested the prediction of the oscillatory interference model (Burgess et al., 2005, 2007; O’Keefe and Burgess, 2005) for “decreasing intrinsic frequency…as you move from the postrhinal border.” The prediction was supported by intracellular data gathered by Lisa Giocomo in my lab showing decreasing frequency of resonance and membrane potential oscillations (MPO) in stellate cells along the dorsal to ventral axis of medial entorhinal cortex (Giocomo et al., 2007; Giocomo and Hasselmo, 2008). The frequency gradient is flattened by knockout of the HCN1 subunit (Giocomo and Hassemo, 2009). A gradient has also been shown in other labs (Boehlen et al., 2010; Garden et al. 2008). Shifts in resonance frequency with acetylcholine (Heys et al., 2010) could underlie the increase in grid cell spacing with novelty (Barry et al., 2010). Subsequent modelling showed that oscillations cannot maintain separate phases within single neurons, motivating the proposal that persistent spiking in separate neurons could provide interacting frequencies to generate grid cells (Hasselmo, 2008), consistent with persistent spiking data in entorhinal cortex (Yoshida et al., 2008) and postsubiculum (Yoshida and Hasselmo, 2009). Single cell MPOs and persistent spiking are too noisy to maintain accurate grid cell firing (Zilli et al., 2009) motivating a model using interactions of network oscillations (Zilli and Hasselmo, in review).

Mark Brandon tested the role of network oscillations in grid cell firing by combining the recording of grid cells with infusion of muscimol to inactivate the medial septum (Brandon et al., 2010). These infusions cause a striking loss of grid cell firing, supporting the role of septal regulation of theta rhythm oscillations in grid cell generation. Simulation in the model of the loss of grid patterning during infusion required removing velocity modulation of frequency. Further analysis of our data after medial septum inactivation revealed that velocity modulation of grid cell spiking rate appears to be eliminated in some cases. Mark Brandon also analyzed the potential role of turning behavior in causing fragmentation of grid cell maps. He tested the effect of smooth versus sharp turns in a spiral maze. Sharp turns did not cause resetting in this task, but the smooth turns demonstrated selectivity of border cells for concave versus convex surfaces and the turns caused angular shifts in grid cell firing fields.


Brandon MP, Bogaard A & Hasselmo ME. Grid cell firing in the medial entorhinal cortex altered by direct pharmacological infusions into the medial septum. FENS Abstr., 5, 025.7, 201

Giocomo, L.M., Hasselmo, M.E. (2008) Time constant of I(h) differs along dorsal to ventral axis of medial entorhinal cortex. J. Neurosci . , 28:9414-25

Giocomo L.M., Hasselmo M.E. (2009) Knock-out of HCN1 subunit flattens dorsal-ventral frequency gradient of medial entorhinal neurons in adult mice. J Neurosci . 29(23):7625-30.

Giocomo LM, Zilli EA, Fransen E, Hasselmo ME. (2007) Temporal frequency of subthreshold oscillations scales with entorhinal grid cell field spacing. Science , 315:1719-22.

Hasselmo M.E. (2008) Grid cell mechanisms and function: Contributions of entorhinal persistent spiking and phase resetting. Hippocampus. 2008;18(12):1213-29. Heys, J.G., Giocomo, L.M., Hasselmo, M.E. (2010) Cholinergic modulation of the resonance properties of stellate cells in layer II of medial entorhinal cortex. J. Neurophysiol. In press. Yoshida, M., Fransen, E., Hasselmo, M.E. (2008) mGluR-dependent persistent firing in entorhinal cortex layer III neurons. Eur. J. Neurosci. 28( 6): 1116-26. Yoshida M., Hasselmo M.E. (2009) Persistent firing supported by an intrinsic cellular mechanism in a component of the head direction system. J Neurosci. 29(15):4945-52. Zilli E.A., Yoshida, M., Tahvildari, B., Giocomo, L.M., Hasselmo, M.E. (2009) Evaluation of the oscillatory interference model of grid cell firing through analysis and measured period variance of some biological oscillators. PLoS Comput Biol. 5(11): e1000573.