Inhibitory Gradient along the Dorsoventral Axis in the Medial Entorhinal Cortex

Beed, Prateep; Gundlfinger, Anja; Schneiderbauer, Sophie; Song, Jie; Böhm, Claudia; Burgalossi, Andrea; Brecht, Michael; Vida, Imre; Schmitz, Dietmar

doi:10.1016/j.neuron.2013.06.038

Cited by 87 publications

(128 citation statements)

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“…Mechanisms underlying hyperexcitability of neurons in superficial MEA seem to be layer-specific: while LII stellate cells are rendered hyperexcitable because of reduced inhibition, LIII pyramidal neurons are rendered hyperexcitable on account of enhanced excitation. The apparent distinction in how alterations in synaptic drive mediate hyperexcitability of these neurons complements the observation that under normal conditions, inhibitory synaptic drive in LII stellate cells is significantly greater than in LIII pyramidal neurons (Beed et al 2013;Couey et al 2013), as confirmed in our recordings of baseline synaptic drive to these neurons in control animals. Previous studies have proposed synaptic reorganization of PrS afferents contacting surviving neurons in LIII and neighboring LII following loss of LIII neurons as a potential mechanism for MEA hyperexcitability (Scharfman et al 1998;Tolner et al 2005).…”

Section: Discussionsupporting

confidence: 80%

“…Alterations in release probability potentially influence spontaneous synaptic activity, but baseline sEPSC frequency for LII stellate cells in epileptic rats was similar to controls. Besides altered release probability, changes in calcium buffering and signal integration properties (Blitz et al 2004;Regehr 2012) may also contribute to increased paired-pulse facilitation in LII stellate cells under epileptic conditions. The large-amplitude epileptogenic events observed in LII and LIII neurons following PrS stimulation exclusively in epileptic rats likely reflect network hyperexcitability and hypersynchrony within the MEA (Bragin et al 1999;Kumar and Buckmaster 2006), similar to PrS-triggered aberrant MEA activity described previously (Scharfman et al 1998;Tolner et al 2007;Tolner et al 2005).…”

Section: Discussionmentioning

confidence: 99%

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Layer-specific modulation of entorhinal cortical excitability by presubiculum in a rat model of temporal lobe epilepsy

Abbasi

Kumar

2015

Journal of Neurophysiology

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Abbasi S, Kumar SS. Layer-specific modulation of entorhinal cortical excitability by presubiculum in a rat model of temporal lobe epilepsy. J Neurophysiol 114: 2854 -2866, 2015. First published September 16, 2015 doi:10.1152/jn.00823.2015 is the most common form of epilepsy in adults and is often refractory to antiepileptic medications. The medial entorhinal area (MEA) is affected in TLE but mechanisms underlying hyperexcitability of MEA neurons require further elucidation. Previous studies suggest that inputs from the presubiculum (PrS) contribute to MEA pathophysiology. We assessed electrophysiologically how PrS influences MEA excitability using the rat pilocarpine model of TLE. PrS-MEA connectivity was confirmed by electrically stimulating PrS afferents while recording from neurons within superficial layers of MEA. Assessment of alterations in PrS-mediated synaptic drive to MEA neurons was made following focal application of either glutamate or NBQX to the PrS in control and epileptic animals. Here, we report that monosynaptic inputs to MEA from PrS neurons are conserved in epileptic rats, and that PrS modulation of MEA excitability is layer-specific. PrS contributes more to synaptic inhibition of LII stellate cells than excitation. Under epileptic conditions, stellate cell inhibition is significantly reduced while excitatory synaptic drive is maintained at levels similar to control. PrS contributes to both synaptic excitation and inhibition of LIII pyramidal cells in control animals. Under epileptic conditions, overall excitatory synaptic drive to these neurons is enhanced while inhibitory synaptic drive is maintained at control levels. Additionally, neither glutamate nor NBQX applied focally to PrS now affected EPSC and IPSC frequency of LIII pyramidal neurons. These layer-specific changes in PrS-MEA interactions are unexpected and of significance in unraveling pathophysiological mechanisms underlying TLE. temporal lobe epilepsy; presubiculum; glutamate application; hyperexcitability; electrophysiology TEMPORAL LOBE EPILEPSY (TLE) is characterized by spontaneous recurrent seizures emanating from temporal lobe foci. It is the most common form of epilepsy in adults, and is often associated with drug-resistant seizures (Engel 1998;Engel et al. 2008).

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Layer-specific modulation of entorhinal cortical excitability by presubiculum in a rat model of temporal lobe epilepsy

Abbasi

Kumar

2015

Journal of Neurophysiology

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“…PV interneurons differentially target stellate cells along the D/V axis of mEC. Dorsal stellate cells receive a greater number of and more widespread PV inhibitory synaptic contacts compared to ventral stellate cells (Beed et al, 2013). The stronger inhibition in dorsal stellates could lead to faster rebound spiking and smaller spacing between grid cell firing fields compared to ventral stellate cells.…”

Section: Discussionmentioning

confidence: 99%

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

Shay

Ferrante

Chapman

et al. 2016

Neurobiology of Learning and Memory

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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.

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“…Extracellular recordings indicate that grid cells occupy modules with similar spatial scales Stensola et al, 2012) that exhibit strong relative spatial stability even when unstable with respect to the environment (Yoon et al, 2013). The density of grid cells is highest in mEC layer II, where they appear to be stellate and pyramidal cells (Domnisoru et al, 2013) with relatively few monosynaptic excitatory interactions but significant disynaptic recurrent inhibitory connectivity (Dhillon and Jones, 2000;Beed et al, 2010;Quilichini et al, 2010;Beed et al, 2013;Couey et al, 2013;Pastoll et al, 2013). These properties are consistent with CAN models of grid cell firing (Fuhs and Touretzky, 2006;McNaughton et al, 2006;Guanella et al, 2007;Burak and Fiete, 2009;Pastoll et al, 2013).…”

Section: Can Dynamicsmentioning

confidence: 99%

A Hybrid Oscillatory Interference/Continuous Attractor Network Model of Grid Cell Firing

2014

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Grid cells in the rodent medial entorhinal cortex exhibit remarkably regular spatial firing patterns that tessellate all environments visited by the animal. Two theoretical mechanisms that could generate this spatially periodic activity pattern have been proposed: oscillatory interference and continuous attractor dynamics. Although a variety of evidence has been cited in support of each, some aspects of the two mechanisms are complementary, suggesting that a combined model may best account for experimental data. The oscillatory interference model proposes that the grid pattern is formed from linear interference patterns or "periodic bands" in which velocity-controlled oscillators integrate self-motion to code displacement along preferred directions. However, it also allows the use of symmetric recurrent connectivity between grid cells to provide relative stability and continuous attractor dynamics. Here, we present simulations of this type of hybrid model, demonstrate that it generates intracellular membrane potential profiles that closely match those observed in vivo, addresses several criticisms aimed at pure oscillatory interference and continuous attractor models, and provides testable predictions for future empirical studies.

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Inhibitory Gradient along the Dorsoventral Axis in the Medial Entorhinal Cortex

Cited by 87 publications

References 41 publications

Layer-specific modulation of entorhinal cortical excitability by presubiculum in a rat model of temporal lobe epilepsy

Layer-specific modulation of entorhinal cortical excitability by presubiculum in a rat model of temporal lobe epilepsy

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

A Hybrid Oscillatory Interference/Continuous Attractor Network Model of Grid Cell Firing

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