Time‐dependent inhibition of hippocampal LTP in vitro following contextual fear conditioning in the rat

Abstract

The effects of contextual fear-learning on hippocampal synaptic excitability were investigated by means of high frequency tetanic stimulation (HFS) in rat brain slices (hippocampal CA1 region), prepared at different intervals (immediately, 24 h or 7 days) after a one-trial contextual fear conditioning paradigm session. In the latter, rats that had previously received aversive electrical footshocks in the experimental apparatus exhibited freezing (the conditioned response) when placed again in the same apparatus (retrieval test). It was shown that contextual fear-learning affects the hippocampal synaptic response. In fact, the HFS produced a decrease in the amplitude of short-term (STP) and long-term potentiation (LTP) when compared to control "naïve" subject values. This decrease in STP amplitude could be observed only in slices prepared immediately after the training session. A decrease in the amplitude of long-term but not short-term potentiation was also observed at 24 h. At 7 days, no decreases in amplitude were observed. These modifications may be thought of as specifically associated with the learning process as they were not recorded in brain preparations from "shock-only" rats (i.e. those that received the same number of aversive stimuli of equal intensity as the conditioned group but with the shocks compressed temporally so that the shocked subjects could not associate nociceptive stimulation and surroundings - no conditioned freezing during retention testing). In "exploration" preparations (brain slices from rats having only freely explored the experimental apparatus without receiving any adverse stimulation) a decrease in LTP amplitude was recorded only immediately after the training session, and STP was never modified. The synaptic response modifications do not appear to be due to presynaptic events, as they are not associated with paired-pulse facilitation curve (PPF) modifications. The present results show that contextual fear conditioning and exploration of a novel environment (i) reduce the ability to induce synaptic plasticity; (ii) differentially influence STP and LTP and that (iii) the persistence of synaptic modifications depends on an animal's prior experience.

How the mechanisms of long-term synaptic potentiation and depression serve experience-dependent plasticity in primary visual cortex

“…This approach has been taken to establish, for example, that one-trial learning in the hippocampus [48,49] induces plasticity akin to LTP. A biochemical signature of LTD is the loss of surface expressed AMPAR and concomitant changes in AMPAR subunit phosphorylation at specific residues, and these same changes have been observed in visual cortex following brief MD [50].…”

Cerebellum and emotional behavior

“…Synaptic changes were localized to vermal lobules V and VI, an area that receives convergence of acoustic and nociceptive stimuli Stowell 1944 andSaab andWillis 2003) and it is related to the expression of emotional behavior Sebastiani et al 1992). Learning-induced synaptic plasticity has been described in amygdala (Rogan et al 1997 andMcKernan andShinnick-Gallagher 1997) and hippocampus (Sacchetti et al 2001, Sacchetti et al 2002band Whitlock et al 2006. Thus, fear learning may be associated with similar neural mechanisms in several different brain structures.…”

Induction of Long-Term Memory by Exposure to Novelty Requires Protein Synthesis: Evidence for a Behavioral Tagging

“…Given that LTP is considered a physiological cellular model of learning and memory formation (Martin et al, 2000;Sacchetti et al, 2002;Gruart et al, 2006;Morris, 2006) and that one-trial inhibitory avoidance training was shown to induce LTP in CA1 in vivo (Whitlock et al, 2006), we used this task to test the prediction that a behavioral analog of the synaptic tagging and capture hypothesis, a key property of synaptic plasticity, occurs in vivo.…”