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In vivo cholinergic modulation of the cellular properties of medial entorhinal cortex neurons
Author(s) -
Tsuno Yusuke,
Schultheiss Nathan W.,
Hasselmo Michael E.
Publication year - 2013
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2012.250431
Subject(s) - entorhinal cortex , neuroscience , cholinergic , in vivo , electrophysiology , cholinergic neuron , biology , chemistry , hippocampus , microbiology and biotechnology
Key points• Medial entorhinal cortex neurons show special intrinsic properties in vitro , which might be important for contributing to functional cell properties, such as grid cell firing. • Both intrinsic properties in slices of medial entorhinal cortex and grid cell activity in vivo are affected by cholinergic activation, but the relationships between these effects are unknown. • Using intracellular recording, we show that intrinsic properties including sag amplitude, sag time constant and resonance frequency are affected by cholinergic activation in vivo , and these results are consistent with in vitro studies. • Furthermore, we show that the relationship between firing frequency and input current is also changed by cholinergic activation in our in vivo recordings. • These results suggest the importance of cholinergic influences on the intrinsic properties of medial entorhinal neurons, and help us understand how this influence contributes to mechanisms of spatial memory and the cause of memory impairment.Abstract Extensive in vitro data and modeling studies suggest that intrinsic properties of medial entorhinal cortex (MEC) neurons contribute to the spiking behaviour of functional cell types of MEC neurons, such as grid cells, recorded in behaving animals. It remains unclear, however, how intrinsic properties of MEC neurons influence cellular dynamics in intact networks in vivo . In order to begin to bridge the gap between electrophysiological data sets from brain slices and behaving animals, in the present study we performed intracellular recordings using sharp electrodes in urethane‐anaesthetized rats to elucidate the cellular dynamics of MEC neurons in vivo . We focused on the h‐current‐dependent sag potential during hyperpolarizing current steps, subthreshold resonance in response to oscillatory frequency sweeps (chirp stimuli), persistent spiking in response to brief depolarizing inputs and the relationship between firing frequency and input ( f–I curve), each of which is sensitive to cholinergic modulation in vitro . Consistent with data from in vitro studies, cholinergic activation by systemic application of the acetylcholinesterase inhibitor, physostigmine, resulted in decreased sag amplitude, increased sag time constant and a decrease of the peak resonance frequency. The f–I curve was also modulated by physostigmine in many neurons, but persistent spiking was not observed in any of our recordings, even when picrotoxin, a GABA A blocker, was included in the internal solution of the recording pipette to reduce possible effects of network inhibition. These results suggest that intrinsic oscillatory and rate‐coding mechanisms, but not intrinsic bistability, are significantly modulated by acetylcholine in the intact entorhinal network.