Short Trains of Theta Frequency Stimulation Enhance CA1 Pyramidal Neuron Excitability in the Absence of Synaptic Potentiation

Abstract

Although plasticity at excitatory synapses is widely studied as a mechanism for memory formation, less is known about the properties and mechanisms underlying activity-dependent changes in excitability. Using extracellular and intracellular recordings in hippocampal slices, we find that short trains (2-3 s) of Schaffer collateral fiber stimulation delivered at 5 Hz induce a robust and persistent increase in the excitability of CA1 pyramidal cells in the absence of synaptic potentiation. This change in excitability is input specific, NMDA receptor dependent, and is not accompanied by lasting changes in either inhibitory synaptic transmission or somatic excitability. Although many of these properties are similar to those seen in synaptic long-term potentiation (LTP), the increase in CA1 pyramidal cell excitability was not blocked by inhibitors of several protein kinases required for the induction of LTP by theta frequency stimulation. Instead, 5 Hz stimulation-induced changes in neuronal excitability were blocked by inhibitors of the protein phosphatase calcineurin. Together, our results suggest that very brief bouts of theta frequency synaptic activity induce a selective, persistent, and dendritically localized increase in CA1 pyramidal cell excitability that might have an important role in both information storage and metaplasticity.

More than synaptic plasticity: role of nonsynaptic plasticity in learning and memory

“…In CA1 neurons, E-S potentiation could be induced by short trains of synaptic stimulation of Schaffer collateral fibers at theta frequency [76]. Because the increase in E-S potentiation was not associated with a change in synaptic strength or with a generalized change in somatic excitability, these results suggest that a local increase in dendritic excitability can be produced by specific patterns of activity in the absence of synaptic plasticity.…”

Associative spike timing-dependent potentiation of the basal dendritic excitatory synapses in the hippocampus in vivo

“…The facilitation of single-PS response in the presence of CPP differed from a lack of spiking during 5-Hz stimulation in vitro (Zhou et al 2005). However, the sensitivity of the spike bursts during 5-Hz stimulation to NMDA receptor blockade was similar in vivo and in vitro (Fink and O'Dell 2009;Thomas et al 1998). While the site (pre-or postsynaptic) of NMDA receptor blockade is not known, it appears that both the attenuation of spike bursts and the blockade of Ca 2ϩ influx through the postsynaptic NMDA receptors may be necessary to block pairing-induced LTP (Fig.…”

Diverse impact of neuronal activity at θ frequency on hippocampal long‐term plasticity

“…A relatively short, 5–15‐sec episode of TPS was sufficient to induce robust synaptic LTP in brain slices from young animals that was comparable in magnitude to HFS–LTP (Watabe et al, ; Watabe and O'Dell, ; Wiltgen et al, ). Further analysis revealed that TPS lasting for 15–30 sec saturated synaptic TPS–LTP (Moody et al, ; Fink and O'Dell, ). However, the effect of longer TPS on synaptic weight critically depends on the length of the TPS episode (see Table for details).…”

“…However, the effect of longer TPS on synaptic weight critically depends on the length of the TPS episode (see Table for details). For instance, TPS of 60–150 sec could still produce LTP of EPSPs (Larson et al, ; Thomas et al, ; Xu et al, ), but prolonging TPS did not result in any further changes in excitatory synaptic transmission in young animals (Fink and O'Dell, ), although LTP was observed in aged animals (see below for details; Watabe and O'Dell, ). As mentioned above, the BCM model predicts that the threshold for LTP increases in a use‐dependent manner with regard to synaptic activity and that prolonged synaptic activity decreases the probability of inducing LTP.…”