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

Jedlicka P, Benuskova L, Abraham WC - PLoS Comput. Biol. (2015)

Bottom Line: It remains uncertain, however, which particular activity rules are utilized by hippocampal neurons to induce LTP and LTD in behaving animals.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe University Frankfurt, Frankfurt, Germany.

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.

No MeSH data available.


Related in: MedlinePlus

Biophysically realistic granule cell model for generating LTP on the medial path and concurrent LTD on the lateral path.(A) Top: Compartmental model of a granule cell with reduced morphology as introduced by Aradi and Holmes [28] and adapted by Santhakumar et al. [29]. See Methods for details. Red and black dots on the dendrites represent positions for medial and lateral perforant path synapses, respectively. (A) Bottom: Three HFS protocols applied to the medial path were used to test for LTP on the medial path and concurrent LTD on the lateral path: 400-DBS, 100-TBS and 400-TBS [25]. (B) Perforant path synaptic weights on a simulated granule cell before, during and after 400-DBS of the medial perforant path. Top: 400-DBS delivered to all medial path synapses produced smaller LTP on the medial path than concurrent LTD on the lateral path. Middle: 400-DBS delivered to 60% of medial path synapses produced greater LTP than concurrent LTD. Bottom: There was a loss of lateral path LTD when ongoing activity in that pathway was set to zero after the onset of 400-DBS (no lateral activity), demonstrating the need for ongoing spontaneous synaptic activity to drive LTD in the non-tetanized synapses. All graphs depict average values for all given synapses over 3 runs. (C) The spatial distribution of synaptic weight changes for 400-DBS delivered to 60% of medial path synapses, showing that non-tetanized medial synapses exhibit LTD. Weight changes are expressed as%change with respect to their baseline value.
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pcbi.1004588.g001: Biophysically realistic granule cell model for generating LTP on the medial path and concurrent LTD on the lateral path.(A) Top: Compartmental model of a granule cell with reduced morphology as introduced by Aradi and Holmes [28] and adapted by Santhakumar et al. [29]. See Methods for details. Red and black dots on the dendrites represent positions for medial and lateral perforant path synapses, respectively. (A) Bottom: Three HFS protocols applied to the medial path were used to test for LTP on the medial path and concurrent LTD on the lateral path: 400-DBS, 100-TBS and 400-TBS [25]. (B) Perforant path synaptic weights on a simulated granule cell before, during and after 400-DBS of the medial perforant path. Top: 400-DBS delivered to all medial path synapses produced smaller LTP on the medial path than concurrent LTD on the lateral path. Middle: 400-DBS delivered to 60% of medial path synapses produced greater LTP than concurrent LTD. Bottom: There was a loss of lateral path LTD when ongoing activity in that pathway was set to zero after the onset of 400-DBS (no lateral activity), demonstrating the need for ongoing spontaneous synaptic activity to drive LTD in the non-tetanized synapses. All graphs depict average values for all given synapses over 3 runs. (C) The spatial distribution of synaptic weight changes for 400-DBS delivered to 60% of medial path synapses, showing that non-tetanized medial synapses exhibit LTD. Weight changes are expressed as%change with respect to their baseline value.

Mentions: To simulate heterosynaptic plasticity with a more complex type of model neuron, we adopted a published, multicompartmental and biophysically realistic computational NEURON model of a dentate gyrus granule cell, albeit with reduced morphology (Fig 1A and Methods; [28, 29]). This nine-section, 125 compartment granule cell model received input from 150 medial path synapses and 150 lateral path synapses, distributed in appropriate zones across the two dendritic branches (Fig 1A). This model was endowed with a synaptic plasticity mechanism containing a presynaptically centered nearest-neighbor implementation of the STDP rule with fast homeostasis (metaplasticity), the same as used previously for the point model [12] and described in the Methods. The multicompartmental granule cell model included the biophysics of the main ion channels in the dendrites and soma. Action potentials were generated in the soma and back-propagated along the dendrites, both electrotonically as well as due to the action of dendritic sodium and calcium ion channels. Thus the granule cell model took into account all of the complex spatio-temporal integration of EPSPs in the dendrites that are evoked by the spontaneous activity, the experimental high-frequency stimulation (HFS) protocol, and the back-propagating postsynaptic spikes. In addition, we employed a realistic simulation of the granule cell spontaneous input activity according to in vivo data that show a significant peak around 8 Hz for both the medial and lateral pathways [2]. For the initial series of simulations, the dendritic voltage threshold for the postsynaptic event detection at a synapse for local STDP implementation was -37 mV. To implement the global metaplasticity mechanism, the somatic voltage threshold for action potential detection for BCM homeostasis calculations was 0 mV.


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

Jedlicka P, Benuskova L, Abraham WC - PLoS Comput. Biol. (2015)

Biophysically realistic granule cell model for generating LTP on the medial path and concurrent LTD on the lateral path.(A) Top: Compartmental model of a granule cell with reduced morphology as introduced by Aradi and Holmes [28] and adapted by Santhakumar et al. [29]. See Methods for details. Red and black dots on the dendrites represent positions for medial and lateral perforant path synapses, respectively. (A) Bottom: Three HFS protocols applied to the medial path were used to test for LTP on the medial path and concurrent LTD on the lateral path: 400-DBS, 100-TBS and 400-TBS [25]. (B) Perforant path synaptic weights on a simulated granule cell before, during and after 400-DBS of the medial perforant path. Top: 400-DBS delivered to all medial path synapses produced smaller LTP on the medial path than concurrent LTD on the lateral path. Middle: 400-DBS delivered to 60% of medial path synapses produced greater LTP than concurrent LTD. Bottom: There was a loss of lateral path LTD when ongoing activity in that pathway was set to zero after the onset of 400-DBS (no lateral activity), demonstrating the need for ongoing spontaneous synaptic activity to drive LTD in the non-tetanized synapses. All graphs depict average values for all given synapses over 3 runs. (C) The spatial distribution of synaptic weight changes for 400-DBS delivered to 60% of medial path synapses, showing that non-tetanized medial synapses exhibit LTD. Weight changes are expressed as%change with respect to their baseline value.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4636250&req=5

pcbi.1004588.g001: Biophysically realistic granule cell model for generating LTP on the medial path and concurrent LTD on the lateral path.(A) Top: Compartmental model of a granule cell with reduced morphology as introduced by Aradi and Holmes [28] and adapted by Santhakumar et al. [29]. See Methods for details. Red and black dots on the dendrites represent positions for medial and lateral perforant path synapses, respectively. (A) Bottom: Three HFS protocols applied to the medial path were used to test for LTP on the medial path and concurrent LTD on the lateral path: 400-DBS, 100-TBS and 400-TBS [25]. (B) Perforant path synaptic weights on a simulated granule cell before, during and after 400-DBS of the medial perforant path. Top: 400-DBS delivered to all medial path synapses produced smaller LTP on the medial path than concurrent LTD on the lateral path. Middle: 400-DBS delivered to 60% of medial path synapses produced greater LTP than concurrent LTD. Bottom: There was a loss of lateral path LTD when ongoing activity in that pathway was set to zero after the onset of 400-DBS (no lateral activity), demonstrating the need for ongoing spontaneous synaptic activity to drive LTD in the non-tetanized synapses. All graphs depict average values for all given synapses over 3 runs. (C) The spatial distribution of synaptic weight changes for 400-DBS delivered to 60% of medial path synapses, showing that non-tetanized medial synapses exhibit LTD. Weight changes are expressed as%change with respect to their baseline value.
Mentions: To simulate heterosynaptic plasticity with a more complex type of model neuron, we adopted a published, multicompartmental and biophysically realistic computational NEURON model of a dentate gyrus granule cell, albeit with reduced morphology (Fig 1A and Methods; [28, 29]). This nine-section, 125 compartment granule cell model received input from 150 medial path synapses and 150 lateral path synapses, distributed in appropriate zones across the two dendritic branches (Fig 1A). This model was endowed with a synaptic plasticity mechanism containing a presynaptically centered nearest-neighbor implementation of the STDP rule with fast homeostasis (metaplasticity), the same as used previously for the point model [12] and described in the Methods. The multicompartmental granule cell model included the biophysics of the main ion channels in the dendrites and soma. Action potentials were generated in the soma and back-propagated along the dendrites, both electrotonically as well as due to the action of dendritic sodium and calcium ion channels. Thus the granule cell model took into account all of the complex spatio-temporal integration of EPSPs in the dendrites that are evoked by the spontaneous activity, the experimental high-frequency stimulation (HFS) protocol, and the back-propagating postsynaptic spikes. In addition, we employed a realistic simulation of the granule cell spontaneous input activity according to in vivo data that show a significant peak around 8 Hz for both the medial and lateral pathways [2]. For the initial series of simulations, the dendritic voltage threshold for the postsynaptic event detection at a synapse for local STDP implementation was -37 mV. To implement the global metaplasticity mechanism, the somatic voltage threshold for action potential detection for BCM homeostasis calculations was 0 mV.

Bottom Line: It remains uncertain, however, which particular activity rules are utilized by hippocampal neurons to induce LTP and LTD in behaving animals.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe University Frankfurt, Frankfurt, Germany.

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.

No MeSH data available.


Related in: MedlinePlus