Voltage dependence of subthreshold resonance frequency in layer ii of medial entorhinal cortex

Abstract

The resonance properties of individual neurons in entorhinal cortex may contribute to their functional properties in awake, behaving rats. Models propose that entorhinal grid cells could arise from shifts in the intrinsic frequency of neurons caused by changes in membrane potential due to depolarizing input from neurons coding velocity. To test for potential changes in intrinsic frequency we measured the resonance properties of neurons at different membrane potentials in neurons in medial and lateral entorhinal cortex. In medial entorhinal neurons the resonant frequency of individual neurons decreased in a linear manner as the membrane potential was depolarized between −70 and −55 mV. At more hyperpolarized membrane potentials, cells asymptotically approached a maximum resonance frequency. Consistent with previous studies, near resting potential the cells of the medial EC possessed a decreasing gradient of resonance frequency along the dorsal to ventral axis, and cells of the lateral EC lacked resonant properties regardless of membrane potential or position along the medial to lateral axis within lateral EC. Application of 10 µM ZD7288, the H-channel blocker, abolished all resonant properties in MEC cells, and resulted in physiological properties very similar to lateral EC cells. These results on resonant properties show a clear change in frequency response with depolarization that could contribute to generation of grid cell firing properties in the medial entorhinal cortex.

Firing properties of entorhinal cortex neurons and early alterations in an Alzheimer's disease transgenic model

“…We provide clear evidence that differences in AP waveform between SCs and FCs in adult mice determine the differences in firing regularity and frequency, both of them significantly increased in SCs. In good agreement with data from rat brain slices [37], we found that the rheobase of FCs is significantly lowered, mainly because of the higher resting membrane resistance, indicating that these neurons are more prone to repetitive firing than SCs. On the other hand, during maximal current injection, SCs initially fire at higher frequency than FCs, but adapt more rapidly to steady-state frequencies.…”

Neuronal rebound spiking, resonance frequency and theta cycle skipping may contribute to grid cell firing in medial entorhinal cortex

“…To address these data, electronic supplementary material, figure S1 ( parts A,B,C) shows the circuit simulated using parameters matching the slower resonance frequency of a cell in bat medial entorhinal cortex [52], as simulated in figure 1d(i)(ii). For comparison, electronic supplementary material, figure S1 part D shows the circuit model with the parameters of theta frequency resonance from figure 2 (and figure 1c(i)(ii)) that match rat dorsal medial entorhinal cortex [31,37]. The models show the same functional ability to switch between different phases of activity, as long as the frequency of medial septal input is altered to be close to the frequency based on the intervals between rebound depolarizations.…”

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

“…The strong inhibitory innervation of stellate cells coupled with their intrinsic properties suggests a functional role for rebound spiking. Rebound spikes occur in response to release from hyperpolarizing current pulses and are dependent on the presence of the h-current ( I h , Alonso & Llinás, 1989; Klink & Alonso, 1993; Shay, Boardman, James, & Hasselmo, 2012). Recent models have simulated grid cell firing behaviors using phase interactions between theta oscillations and stellate cell rebound spikes (Hasselmo, 2013; Hasselmo & Shay, 2014).…”