Persistent modifications of hippocampal synaptic function during remote spatial memory

Abstract

A widely accepted notion for a process underlying memory formation is that learning changes the efficacy of synapses by the mechanism of synaptic plasticity. While there is compelling evidence of changes in synaptic efficacy observed after learning, demonstration of persistent synaptic changes accompanying memory has been elusive. We report that acquisition of a hippocampus and long-term potentiation dependent memory for places persistently changes the function of CA1 synapses. Using extracellular recordings we measured CA3-CA1 and EC-CA1 synaptic responses and found robust changes in the CA3-CA1 pathway after memory training. Crucially, these changes in synaptic function lasted at least a month and coincided with the persistence of long-term place memories; the changes were only observed in animals that expressed robust memory, and not in animals with poor memory recall. Interestingly, our findings were observed at the level of populations of synapses; suggesting that memory formation recruits widespread synaptic circuits and persistently reorganizes their function to store information.

Persistent increased PKMζ in long-term and remote spatial memory

“…Like the persistent increases in PKMζ (Fig. 1B), these persistent alterations in synaptic function do not require memory retrieval (Pavlowsky et al, 2017). These very long-term alterations in synaptic function coincide with the storage of remote memory because they are not detected in animals with poor memory recall at 1 month (Pavlowsky et al, 2017).…”

“…These increases in PKMζ during remote memory maintenance persist far longer than the increases of c-Fos (Kovacs, 2008) or Arc (Shepherd & Bear, 2011), which last for only hours after experience, and may equal or exceed even the long-lived increase of ΔFosB, a transcription factor that persistently increases for at least 1 day after training (Eagle et al, 2015) and for several weeks after chronic exposure to drugs of abuse (Nestler, 2008). Active place avoidance training modifies dentate gyrus responses to neocortical stimulation of the perforant path measured 1 day after training in vivo (Park, Burghardt, Dvorak, Hen, & Fenton, 2015), and extended active place avoidance training produces persistent modifications in synaptic circuitry in the CA3-CA1 pathway that can last 1 month (Pavlowsky, Wallace, Fenton, & Alarcon, 2017). Like the persistent increases in PKMζ (Fig.…”

“…1B), these persistent alterations in synaptic function do not require memory retrieval (Pavlowsky et al, 2017). These very long-term alterations in synaptic function coincide with the storage of remote memory because they are not detected in animals with poor memory recall at 1 month (Pavlowsky et al, 2017). Likewise, we find that following training protocols that produce 1-day long-term memory that decays by 1 month, the initial increase in PKMζ observed at 1 day returns to baseline by 1 month (Figs.…”

Reduction of long-term potentiation at Schaffer collateral-CA1 synapses in the rat hippocampus at the acute stage of vestibular compensation

“…Additionally, a lowered threshold of LTP induction or the enhancement of synaptic efficacy in the CA1 area occurs in the initial phase of spatial memory formation [824]. …”

Active place avoidance is no more stressful than unreinforced exploration of a familiar environment

“…This elevation in CORT response in the 1‐trail yoked group was indistinguishable from what was observed in the predator stress group. Importantly, soon after and during training is a relevant time point for many experimental designs that endeavor to assess mechanisms of memory using electrophysiological approaches (Whitlock et al, ; Park et al, ; Pavlowsky et al, ), although interest in molecular mechanisms could drive interest in later time points (Hsieh et al, ; Tsokas et al, ).…”