The idea that new memories undergo a time-dependent consolidation process after acquisition has received considerable experimental support. More controversial has been the demonstration that established memories, once recalled, become labile and sensitive to disruption, requiring “reconsolidation” to become permanent. By infusing antisense oligodeoxynucleotides into the hippocampus of rats, we show that consolidation and reconsolidation are doubly dissociable component processes of memory. Consolidation involves brain-derived neurotrophic factor (BDNF) but not the transcription factor Zif268, whereas reconsolidation recruits Zif268 but not BDNF. These findings confirm a requirement for BDNF specifically in memory consolidation and also resolve the role of Zif268 in brain plasticity, learning, and memory.

The role in spatial divided and sustained attention of D1 and D2-like dopamine (DA) receptors in the rat prelimbic medial prefrontal cortex (mPFC) was investigated in a five-choice serial reaction time task. Rats were trained to detect brief flashes of light (0.5–0.25 sec) presented randomly in a spatial array of five apertures. When performance stabilized, animals received bilateral microinfusions of either the D1 DA receptor antagonist SCH 23390, the D1 DA receptor agonist SKF 38393, or the D2 DA antagonist sulpiride into the mPFC. Rats were divided into two groups, with low (75%) baseline levels of accuracy. Infusions of the D2 receptor antagonist sulpiride had no significant effect on any task variable. SCH 23390 (0.3 μg) selectively impaired the accuracy of attentional performance in rats in the high baseline condition. By contrast, SKF 38393 (0.06 μg) enhanced the accuracy of attentional performance in the low baseline condition, a lower dose (0.03 μg) also increasing the speed of making correct responses. Finally, the beneficial effects of SKF-383893 on choice accuracy were antagonized by SCH 23390 (1.0 μg).The results provide apparently the first demonstration of enhanced cognitive function after local administration of a D1 receptor agonist to the mPFC and suggest dissociable roles of D1 and D2 DA receptors of the mPFC in modulating attentional function.

Since its discovery almost three decades ago, the secreted neurotrophin brain-derived neurotrophic factor (BDNF) has been firmly implicated in the differentiation and survival of neurons of the CNS. More recently, BDNF has also emerged as an important regulator of synaptogenesis and synaptic plasticity mechanisms underlying learning and memory in the adult CNS. In this review we will discuss our knowledge about the multiple intracellular signalling pathways activated by BDNF, and the role of this neurotrophin in long-term synaptic plasticity and memory formation as well as in synaptogenesis. We will show that maturation of BDNF, its cellular localization and its ability to regulate both excitatory and inhibitory synapses in the CNS may result in conflicting alterations in synaptic plasticity and memory formation. Lack of a precise knowledge about the mechanisms by which BDNF influences higher cognitive functions and complex behaviours may constitute a severe limitation in the possibility to devise BDNF-based therapeutics for human disorders of the CNS.

The neuroanatomical and molecular basis of fear memory retrieval was studied by analyzing the expression of the plasticity-associated immediate early gene zif268. Cellular quantitative in situ hybridization revealed thatzif268 is expressed within specific regions of the hippocampus and amygdala during fear memory retrieval. Within the hippocampus, increased expression of zif268 was observed within CA1 neurons, but not dentate gyrus neurons, during the retrieval of contextual, but not cued, fear associations. In contrast,zif268 expression was increased within neurons of the amygdala (lateral, basal, and central nuclei) during the retrieval of both contextual and cued fear memories. These results demonstrate activation of hippocampal CA1 neurons in contextual fear memory retrieval that was not merely a correlate of the behavioral expression of fear itself, because it was limited to the retrieval of contextual, and not cued, fear memories. Further studies revealed that the selective increase in hippocampal CA1 zif268 expression seen after contextual fear memory retrieval was limited to the retrieval of recent (24 hr) but not older (28 d) memories. These experiments represent the first demonstration thatzif268 expression in specific neuronal populations is associated with memory retrieval and suggest that this gene may contribute to plasticity and reconsolidation accompanying the retrieval process.