Long‐lasting hippocampal potentiation and contextual memory consolidation

Abstract

In order to ascertain whether there are hippocampal electrophysiological modifications specifically related to memory, exploratory activity and emotional stress, extracellular electrical activity was recorded in hippocampal slices prepared from the brains of male adult rats. Several groups of animals were employed: (i) rats which had freely explored the experimental apparatus (8 min exposure); (ii) rats which had been subjected, in the same apparatus, to a fear conditioning paradigm training entailing the administration of aversive electrical footshocks (8 min exposure); (iii) rats to which the same number of aversive shocks had been administered in the same apparatus, but temporally compressed so as to make difficult the association between painful stimuli and the apparatus (30 s exposure); (iv) naïve rats never placed in the apparatus. Half of the rats from each treatment group were used for retrieval testing and the other half for hippocampal excitability testing. The conditioned freezing response was exhibited for no less than 4 weeks. Hippocampal excitability was measured by means of input-output curves (IOC) and paired-pulse facilitation curves (PPF). Retrieval testing or brain slices preparation were performed at increasing delays after the training sessions: immediately afterwards or after 1, 7 or 28 days. Only the rats subjected to the fear conditioning training exhibited freezing when placed again in the apparatus (retrieval testing). It was found that IOCs, with respect to naïve rats, increased in the conditioned animals up to the 7-day delay. In free exploration animals the IOCs increased only immediately after the training session. In all other rats no modification of the curves was observed. IOC increases do not appear to imply presynaptic transmitter release modifications, because they were not accompanied by PPF modifications. In conclusion, a clear-cut correlation was found between the increase in excitability of the Schaffer collateral-CA1 dendrite synapses and freezing response consolidation.

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.…”

The role of the nucleus basalis magnocellularis in fear conditioning consolidation in the rat

“…During the first 3-min subperiod of exposure to the new context (without CS, acoustic stimulation), the freezing response was very low in all groups of animals (see below; Fig. 4), and comparable to that of rats allowed to freely explore the conditioning chamber before receiving footshocks (see above) (Sacchetti et al 1999b(Sacchetti et al , 2001(Sacchetti et al , 2002(Sacchetti et al , 2003. These results show the absence of generalization phenomena and the specificity of the freezing response to the acoustic CS in this new context.…”

“…The experimental subjects did not exhibit freezing when Learning & Memory placed in the conditioning apparatus prior to the training session (Corodimas and LeDoux 1995;Sacchetti et al 1999aSacchetti et al , 2001Sacchetti et al , 2002Sacchetti et al , 2003Baldi et al 2007). After the single training session, freezing responses appeared only following the presentation of previously administered stimuli (acoustic CS and context).…”

“…As previously stated, only a single training session acquisition paradigm permits a chronological analysis of the involvement of a given neural structure in memory consolidation. This because the starting time of mnemonic processing is thus exactly defined, while such an exact definition is not possible in the case of repeated acquisition-session paradigms (Bures and Buresova 1990;Ambrogi Lorenzini et al 1999;Sacchetti et al 1999bSacchetti et al , 2001.…”

“…The last 1 sec of each CS was paired with the US as an electric footshock. US intensity was 1.0 mA, as in previous experiments (Sacchetti et al 2001). The rat was left undisturbed for 2 min after the end of the stimulation sequence.…”