A Voltage-Based STDP Rule Combined with Fast BCM-Like Metaplasticity Accounts for LTP and Concurrent "Heterosynaptic" LTD in the Dentate Gyrus In Vivo.

Peter Jedlicka,Wickliffe C Abraham,Lubica Benuskova,Abigail Morrison

doi:10.1371/journal.pcbi.1004588

Peter Jedlicka, Wickliffe C Abraham + Show 2 more

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https://doi.org/10.1371/journal.pcbi.1004588

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Abstract

Long-term potentiation (LTP) and long-term depression (LTD) are widely accepted to be synaptic mechanisms involved in learning and memory. It remains uncertain, however, which particular activity rules are utilized by hippocampal neurons to induce LTP and LTD in behaving animals. Recent experiments in the dentate gyrus of freely moving rats revealed an unexpected pattern of LTP and LTD from high-frequency perforant path stimulation. While 400 Hz theta-burst stimulation (400-TBS) and 400 Hz delta-burst stimulation (400-DBS) elicited substantial LTP of the tetanized medial path input and, concurrently, LTD of the non-tetanized lateral path input, 100 Hz theta-burst stimulation (100-TBS, a normally efficient LTP protocol for in vitro preparations) produced only weak LTP and concurrent LTD. Here we show in a biophysically realistic compartmental granule cell model that this pattern of results can be accounted for by a voltage-based spike-timing-dependent plasticity (STDP) rule combined with a relatively fast Bienenstock-Cooper-Munro (BCM)-like homeostatic metaplasticity rule, all on a background of ongoing spontaneous activity in the input fibers. Our results suggest that, at least for dentate granule cells, the interplay of STDP-BCM plasticity rules and ongoing pre- and postsynaptic background activity determines not only the degree of input-specific LTP elicited by various plasticity-inducing protocols, but also the degree of associated LTD in neighboring non-tetanized inputs, as generated by the ongoing constitutive activity at these synapses.

Highlights

Synaptic plasticity, i.e. long-lasting activity-dependent changes in synaptic transmission, is widely considered to be a critical neural mechanism for memory storage
The vast majority of computational studies that model synaptic plasticity neglect the fact that in vivo neurons exhibit an ongoing spontaneous spiking which affects the dynamics of synaptic changes
The most recent models of plasticity based on the precise timing of pre- and postsynaptic spikes typically ignore the fact that in vivo [1, 2], and sometimes in vitro [3], the studied neurons exhibit an ongoing spontaneous spiking with frequencies reaching up to 10 Hz that has the potential to profoundly influence plasticity outcomes

Summary

Introduction

I.e. long-lasting activity-dependent changes in synaptic transmission, is widely considered to be a critical neural mechanism for memory storage. A key element of this BCM theory is a whole-cell variable termed the modification threshold, the tipping point at which the presynaptic activity either leads to long-term depression (LTD) or long-term potentiation (LTP) of synaptic efficacy. A second key element is the theory’s postulate that the average ongoing level of background activity dynamically sets the position of the LTD/LTP tipping point in such a way that potentiation is favored when background postsynaptic cell firing is low on average and, vice versa, depression is favored when the postsynaptic activity is high on average. The proposal of a modifiable plasticity threshold foreshadowed the concept of metaplasticity [8], developed to account for the abundant experimental evidence that prior neural activity can change the state of neurons and synapses such that the outcome of future synaptic plasticity protocols is altered [9]

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