The strength and efficiency of synaptic connections are affected by the environment or the experience of the individual. This property, called synaptic plasticity, is directly related to memory and learning processes and has been modeled at the cellular level. These types of cellular memory and learning models include specific stimulation protocols that generate a long-term strengthening of the synapses, called long-term potentiation, or a weakening of the said long-term synapses, called long-term depression. Although, for decades, researchers have believed that the main cause of the cognitive deficit that characterizes Alzheimer’s disease (AD) and aging was the loss of neurons, the hypothesis of an imbalance in the cellular and molecular mechanisms of synaptic plasticity underlying this deficit is currently widely accepted. An understanding of the molecular and cellular changes underlying the process of synaptic plasticity during the development of AD and aging will direct future studies to specific targets, resulting in the development of much more efficient and specific therapeutic strategies. In this review, we classify, discuss, and describe the main findings related to changes in the neurophysiological mechanisms of synaptic plasticity in excitatory synapses underlying AD and aging. In addition, we suggest possible mechanisms in which aging can become a high-risk factor for the development of AD and how its development could be prevented or slowed.

The role of serotonin (5-hydroxytryptamine [5-HT]) and 5-HT2A receptors in anxiety has been extensively studied, mostly without considering individual differences in trait anxiety. Our laboratory developed two lines of animals that are bred for high and low freezing responses to contextual cues that are previously associated with footshock (Carioca High-conditioned Freezing [CHF] and Carioca Low-conditioned Freezing [CLF]). The present study investigated whether ketanserin, a preferential 5-HT2A receptor blocker, exerts distinct anxiety-like profiles in these two lines of animals. In the first experiment, the animals received a systemic injection of ketanserin and were exposed to the elevated plus maze (EPM). In the second experiment, these two lines of animals received microinjections of ketanserin in the infralimbic (IL) and prelimbic (PL) cortices and were exposed to either the EPM or a contextual fear conditioning paradigm. The two rat lines exhibited bidirectional effects on anxiety-like behavior in the EPM and opposite responses to ketanserin. Both systemic and intra-IL cortex injections of ketanserin exerted anxiolytic-like effects in CHF rats but anxiogenic-like effects in CLF rats. Microinjections of ketanserin in the PL cortex also exerted anxiolytic-like effects in CHF rats but had no effect in CLF rats. These results suggest that the behavioral effects of 5-HT2A receptor antagonism might depend on genetic variability associated with baseline reactions to threatening situations and 5-HT2A receptor expression in the IL and PL cortices.Highlights CHF and CLF rats are two bidirectional lines that are based on contextual fear conditioning.CHF rats have a more “anxious” phenotype than CLF rats in the EPM.The 5-HT2A receptor antagonist ketanserin had opposite behavioral effects in CHF and CLF rats.Systemic and IL injections either decreased (CHF) or increased (CLF) anxiety-like behavior.PL injections either decreased (CHF) anxiety-like behavior or had no effect (CLF).

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The study of functional connectivity and declarative memory has lately been focused on finding biomarkers of neuropsychological diseases. However, little is known about its patterns in healthy brains. Thus, in this systematic review we analyze and integrate the findings of 81 publications regarding functional connectivity (measured by fMRI during both task and resting-state) and semantic and episodic memory in healthy adults. Moreover, we discriminate and analyze the main areas and links found in specific memory phases (encoding, storage or retrieval) based on several criteria, such as time length, depth of processing, rewarding value of the information, vividness and amount or kind of details retrieved. There is a certain degree of overlap between the networks of episodic and semantic memory and between the encoding and retrieval stages. Although several differences are pointed out during the article, this calls to attention the need for further empirical studies that actively compare both types of memory, particularly using other baseline conditions apart from the traditional resting state. Indeed, the active involvement of the default mode network in both declarative memory and resting condition suggests the possibility that during rest there is an on-going memory processing. We find support for the ‘attention to memory’ hypothesis, the memory differentiation model and the appropriate transfer hypothesis, but some evidence is inconsistent with the traditional hub-and-spoke model.