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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

Postsynaptic membrane voltage during one train of HFS.Simulated voltage traces showing the depolarization and action potentials evoked by 400-DBS (top panel), 100-TBS (middle panel) and 400-TBS (bottom panel) and measured at the soma (black trace) and the dendrite (blue trace). The dendritic voltage was recorded in the middle of the dendritic region targeted by medial path synapses. Note the faithfulness of cell firing for each TBS pulse for the 100-TBS protocol. In simulations of LTP and LTD, the postsynaptic threshold for STDP was set to -37 mV so that STDP could be exhibited by even the most distal of synapses on the dendritic tree.
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pcbi.1004588.g005: Postsynaptic membrane voltage during one train of HFS.Simulated voltage traces showing the depolarization and action potentials evoked by 400-DBS (top panel), 100-TBS (middle panel) and 400-TBS (bottom panel) and measured at the soma (black trace) and the dendrite (blue trace). The dendritic voltage was recorded in the middle of the dendritic region targeted by medial path synapses. Note the faithfulness of cell firing for each TBS pulse for the 100-TBS protocol. In simulations of LTP and LTD, the postsynaptic threshold for STDP was set to -37 mV so that STDP could be exhibited by even the most distal of synapses on the dendritic tree.

Mentions: The multicompartmental model of granule cell, with realistic active and passive properties, was able to reproduce different experimental results arising from the various experimental protocols. This afforded us the opportunity to examine the firing properties of the granule cell model in response to HFS in order to ascertain biophysical explanations for the protocol dependence of the different plasticity outcomes. Of particular interest to us was the integration of postsynaptic action potential firing, which is the key parameter for BCM-based adjustment of the STDP parameters Ap (potentiation-amplitude) and Ad (depression-amplitude). The integrated spike count 〈c〉 (factored by a constant α) for the first protocol, 400-DBS, is shown in the left panel of Fig 4A. The right panel shows the corresponding dynamic changes in Ap and Ad as these latter parameters are scaled by 〈c〉. For this protocol, after the initial period of stabilization, time-averaged 〈c〉 remained steady and was only mildly increased during HFS of the medial path, because each burst of 10 presynaptic pulses (at 400 Hz) generated only 2–4 postsynaptic spikes due to action potential refractoriness (Fig 5, upper panel), and therefore both Ap and Ad barely changed. Thus it can be concluded that the DBS protocol was sufficient to instigate LTP of the medial path using relatively unchanged STDP parameters. Close inspection of the development of LTP and LTD shows that LTD began to arise only after LTP had begun to develop (Fig 6), indicating that the LTD in the lateral path was occurring as a consequence of LTP induction in the medial path. Lateral synapses were depressed because the spontaneous activity of the potentiated medial path started controlling postsynaptic spiking, and so the lateral path activity was participating less in the LTP-inducing pre-post order than in the LTD-inducing post-pre order.


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)

Postsynaptic membrane voltage during one train of HFS.Simulated voltage traces showing the depolarization and action potentials evoked by 400-DBS (top panel), 100-TBS (middle panel) and 400-TBS (bottom panel) and measured at the soma (black trace) and the dendrite (blue trace). The dendritic voltage was recorded in the middle of the dendritic region targeted by medial path synapses. Note the faithfulness of cell firing for each TBS pulse for the 100-TBS protocol. In simulations of LTP and LTD, the postsynaptic threshold for STDP was set to -37 mV so that STDP could be exhibited by even the most distal of synapses on the dendritic tree.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi.1004588.g005: Postsynaptic membrane voltage during one train of HFS.Simulated voltage traces showing the depolarization and action potentials evoked by 400-DBS (top panel), 100-TBS (middle panel) and 400-TBS (bottom panel) and measured at the soma (black trace) and the dendrite (blue trace). The dendritic voltage was recorded in the middle of the dendritic region targeted by medial path synapses. Note the faithfulness of cell firing for each TBS pulse for the 100-TBS protocol. In simulations of LTP and LTD, the postsynaptic threshold for STDP was set to -37 mV so that STDP could be exhibited by even the most distal of synapses on the dendritic tree.
Mentions: The multicompartmental model of granule cell, with realistic active and passive properties, was able to reproduce different experimental results arising from the various experimental protocols. This afforded us the opportunity to examine the firing properties of the granule cell model in response to HFS in order to ascertain biophysical explanations for the protocol dependence of the different plasticity outcomes. Of particular interest to us was the integration of postsynaptic action potential firing, which is the key parameter for BCM-based adjustment of the STDP parameters Ap (potentiation-amplitude) and Ad (depression-amplitude). The integrated spike count 〈c〉 (factored by a constant α) for the first protocol, 400-DBS, is shown in the left panel of Fig 4A. The right panel shows the corresponding dynamic changes in Ap and Ad as these latter parameters are scaled by 〈c〉. For this protocol, after the initial period of stabilization, time-averaged 〈c〉 remained steady and was only mildly increased during HFS of the medial path, because each burst of 10 presynaptic pulses (at 400 Hz) generated only 2–4 postsynaptic spikes due to action potential refractoriness (Fig 5, upper panel), and therefore both Ap and Ad barely changed. Thus it can be concluded that the DBS protocol was sufficient to instigate LTP of the medial path using relatively unchanged STDP parameters. Close inspection of the development of LTP and LTD shows that LTD began to arise only after LTP had begun to develop (Fig 6), indicating that the LTD in the lateral path was occurring as a consequence of LTP induction in the medial path. Lateral synapses were depressed because the spontaneous activity of the potentiated medial path started controlling postsynaptic spiking, and so the lateral path activity was participating less in the LTP-inducing pre-post order than in the LTD-inducing post-pre order.

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