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Post-traumatic stress disorder (PTSD) occurs after exposure to traumatic situations and it is characterized by cognitive deficits that include impaired explicit memory. The neurobiological bases of such PTSD-associated memory alterations are yet to be elucidated and no satisfactory treatment for them exists. To address this issue, we first studied whether a single exposure of young adult rats (60 days) to immobilization on boards (IMO), a putative model of PTSD, produces long-term behavioral effects (2-8 days) similar to those found in PTSD patients. Subsequently, we investigated whether the administration of the TrkB agonist 7,8-dihydroxyflavone (DHF) 8 h after stress (therapeutic window) ameliorated the PTSD-like effect of IMO and the associated changes in synaptic plasticity. A single IMO exposure induced a spatial memory impairment similar to that found in other animal models of PTSD or in PTSD patients. IMO also increased spine density and long-term potentiation (LTP) in the CA3-CA1 pathway. Significantly, DHF reverted both spatial memory impairment and the increase in LTP, while it produced no effect in the controls. These data provide novel insights into the possible neurobiological substrate for explicit memory impairment in PTSD patients, supporting the idea that the activation of the BDNF/TrkB pathway fulfils a protective role after severe stress. Administration of DHF in the aftermath of a traumatic experience might be relevant to prevent its long-term consequences. © 2016 Wiley Periodicals, Inc.

Why memory is a particular target for the pathological changes in Alzheimer's Disease (AD) has long been a fundamental question when considering the mechanisms underlying this disease. It has been established from numerous biochemical and morphological studies that AD is, at least initially, a consequence of synaptic malfunction provoked by Amyloid β (Aβ) peptide. APP/PS1 transgenic mice accumulate Aβ throughout the brain, and they have therefore been employed to investigate the effects of Aβ overproduction on brain circuitry and cognition. Previous studies show that Aβ overproduction affects spine morphology in the hippocampus and amygdala, both within and outside plaques (Knafo et al., (2009) Cereb Cortex 19:586-592; Knafo et al., (in press) J Pathol). Hence, we conducted a detailed analysis of dendritic spines located in the stratum oriens and stratum radiatum of the CA1 hippocampal subfield of APP/PS1 mice. Three-dimensional analysis of 18,313 individual dendritic spines revealed a substantial layer-specific decrease in spine neck length and an increase in the frequency of spines with a small head volume. Since dendritic spines bear most of the excitatory synapses in the brain, changes in spine morphology may be one of the factors contributing to the cognitive impairments observed in this AD model. © 2010 Wiley-Liss, Inc.

The notion that long-term synaptic plasticity is generated by activity-induced molecular modifications is widely accepted. It is well established that neural cell adhesion molecule (NCAM) is one of the prominent modulators of synaptic plasticity. NCAM can be polysialylated (PSA-NCAM), a reaction that provides it with anti-adhesion properties. In this study we have focused on NCAM and on its polysialylated state, and their relation to learning of an olfactory discrimination task, which depends on both the piriform (olfactory) cortex and hippocampus. We trained rats to distinguish between pairs of odors until rule learning was achieved, a process that normally lasts 6-8 days. At four time points, during training and after training completion, synaptic NCAM and PSA-NCAM expression were assessed in the piriform cortex and hippocampus. We report that NCAM modulation is specific to PSA-NCAM, which is upregulated in the hippocampus one day after training completion. We also report a correlation between the performance of individual rats in an early training stage and their NCAM expression, both in the piriform cortex and hippocampus. Since individual early performance in our odor discrimination task is correlated with the performance throughout the training period, we conclude that early NCAM expression is associated with odor learning capability. We therefore suggest that early synaptic NCAM expression may be one of the factors determining the capability of rats to learn.

We have previously shown that rule learning of an olfac- tory discrimination task is accompanied by increased spine density along the apical dendrites of piriform cortex pyramidal neurons. The purpose of the present study was to examine whether such olfactory learning task, in which the hippocampus is actively involved, induces morphological mod- ifications in CA1 pyramidal neurons as well. Rats were trained to discrim- inate positive cues in pairs of odors for a water reward. Morphological modifications were studied in Golgi-impregnated neurons with light mi- croscopy, 1 and 3 days after training completion. Spine densities were measured on the proximal region of apical dendrites and on basal den- drites after rule learning. Three days after training completion, the mean spine density on apical dendrites in neurons from trained rats was signif- icantly higher by 20.5% than in neurons from pseudo-trained and naive animals, which did not differ from each other. By contrast, there was no significant difference in spine density of basal dendrites among the three groups. As length and diameter of spiny dendritic segments did not change after learning, the learning-related increase in spine density in neurons from trained rats may reflect a net increase in the number of excitatory synapses in the hippocampus following olfactory rule learning. © 2004 Wiley-Liss, Inc.