Plasticity of intrinsic excitability in mature granule cells of the dentate gyrus.

Jeffrey Lopez-Rojas,Martin Heine,Michael R. Kreutz

doi:10.1038/srep21615

Abstract

The dentate gyrus is the main entry gate for cortical input to the hippocampus and one of the few brain areas where adult neurogenesis occurs. Several studies have shown that it is relatively difficult to induce synaptic plasticity in mature but not in newborn dentate granule cells. In the present work we have systematically addressed how classical protocols to induce synaptic plasticity affect action potential firing and intrinsic excitability in mature granule cells. We found that stimulation paradigms considered to be relevant for learning processes consistently modified the probability to generate action potentials in response to a given synaptic input in mature cells, in some paradigms even without any modification of synaptic strength. Collectively the results suggest that plasticity of intrinsic dendritic excitability has a lower induction-threshold than synaptic plasticity in mature granule cells and that this form of plasticity might be an important mechanism by which mature granule cells contribute to hippocampal function.

Highlights

The hippocampus integrates and temporally stores information from a variety of subcortical and cortical areas
We first studied the effects of TBS7 on the field excitatory postsynaptic potential in the dentate gyrus and found a modest potentiation 1 hour after Theta-burst stimulation (TBS) (136.8 ± 5.8%) (Fig. 1)
To assess whether non-synaptic forms of plasticity can be induced in mature granule cells we studied the effects of three extensively used long-term potentiation (LTP)-inducing protocols, TBS, a high-frequency stimulation/pairing protocol (HFS-P) and spike-timing dependent plasticity (STDP) on synaptic strength and intrinsic excitability

Summary

Introduction

The hippocampus integrates and temporally stores information from a variety of subcortical and cortical areas. Already the first description of long-term potentiation (LTP) indicated that synaptic plasticity might not be the sole determinant of functional plasticity of granule cells in the dentate gyrus. In their seminal studies Bliss and collaborators observed that occasionally a lasting increase in neuronal excitability occurred without any sign of synaptic potentiation[9,10]. This plasticity of excitability has been largely neglected, especially in the dentate gyrus, despite the fact that action potential generation is the essential output of neuronal activity and that the ability to fire action potentials depends on excitatory synaptic drive, and on inhibitory control and intrinsic membrane properties[11,12]. We explored this phenomenon in the dentate and investigated whether non-synaptic forms of plasticity are prominent in mature granule cells

Methods

Results

Conclusion