Learning to keep your cool: reducing aggression through the experimental modification of cognitive control.

Prior research suggests that recruiting cognitive control resources following exposure to hostile stimuli may allow individuals to more effectively override their aggressive urges. In the current study, a cognitive modification procedure was developed to encourage participants to perform this cognitive operation. It successfully encouraged cognitive control recruitment following hostile primes. More importantly, this procedure allowed individuals prone to hostile attributions to override their aggressive urges. Interestingly, it also led to a slight increase in aggression at low levels of hostile attributions. Discussion focused on theoretical and practical implications of the hypothesised effect, as well as possible explanations for the non-hypothesised effect.

Spine pruning in 5xFAD mice starts on basal dendrites of layer 5 pyramidal neurons.

Transgenic mice with Alzheimer's disease (AD) mutations have been widely used to model changes in neuronal structure and function. While there are clear gross structural changes in post-mortem brains of AD patients, most mouse models of AD do not recapitulate the considerable loss of neurons. Furthermore, possible connections between early subtle structural changes and the loss of neurons are difficult to study. In an attempt to start unraveling how neurons are affected during the early stages of what becomes full neurodegeneration, we crossed a mouse model of familial AD, which displays massive neocortical neurodegeneration (the 5xFAD mouse), with the fluorescent H-line YFP mouse. This novel bigenic mouse model of AD, which we have named the 5XY mouse, expresses YFP in principal neurons in the cortex such that even fine details of cells are clearly visible. Such bright fluorescence allowed us to use high-resolution confocal microscopy to quantify changes in spine density in the somatosensory cortex, prefrontal cortex, and hippocampus at 2, 4, and 6 months of age. A significant loss of spines on basal dendrites in the somatosensory and prefrontal cortices of 6-month-old 5XY female mice was found. There was no observed spine loss at 6 months of age on the oblique dendrites of the hippocampus in the same mice. These data suggest that spine loss is an early event in the degeneration of the neocortical neurons in 5xFAD mice and a likely contributor to the cognitive impairments reported previously in this AD mouse model.

Longitudinal in vivo two-photon fluorescence imaging.

Fluorescence microscopy is an essential technique for the basic sciences, especially biomedical research. Since the invention of laser scanning confocal microscopy in the 1980s, which enabled imaging both fixed and living biological tissue with 3D precision, high-resolution fluorescence imaging has revolutionized biological research. Confocal microscopy, by its very nature, has one fundamental limitation. Due to the confocal pinhole, deep tissue fluorescence imaging is not practical. In contrast (no pun intended), two-photon fluorescence microscopy allows, in principle, the collection of all emitted photons from fluorophores in the imaged voxel, dramatically extending our ability to see deep into living tissue. Since the development of transgenic mice with genetically encoded fluorescent protein in neocortical cells in 2000, two-photon imaging has enabled the dynamics of individual synapses to be followed for up to 2 years. Since the initial landmark contributions to this field in 2002, the technique has been used to understand how neuronal structure are changed by experience, learning, and memory and various diseases. Here we provide a basic summary of the crucial elements that are required for such studies, and discuss many applications of longitudinal two-photon fluorescence microscopy that have appeared since 2002.

In vivo characterization of a bigenic fluorescent mouse model of Alzheimer's disease with neurodegeneration.

The loss of cognitive function in Alzheimer's disease (AD) patients is strongly correlated with the loss of neurons in various regions of the brain. We have created a new fluorescent bigenic mouse model of AD by crossing "H-line" yellow fluorescent protein (YFP) mice with the 5xFAD mouse model, which we call the 5XY mouse model. The 5xFAD mouse has been shown to have significant loss of L5 pyramidal neurons by 12 months of age. These neurons are transgenically labeled with YFP in the 5XY mouse, which enable longitudinal imaging of structural changes. In the 5XY mice, we observed an appearance of axonal dystrophies, with two distinct morphologies in the early stages of the disease progression. Simple swelling dystrophies are transient in nature and are not directly associated with amyloid plaques. Rosette dystrophies are more complex structures that remained stable throughout all imaging sessions, and always surrounded an amyloid plaque. Plaque growth was followed over 4 weeks, and significant growth was seen between weekly imaging sessions. In addition to axonal dystrophy appearance and plaque growth, we were able to follow spine stability in 4-month old 5XY mice, which revealed no significant loss of spines. 5XY mice also showed a striking shrinkage of the neocortex at older ages (12-14 months). The 5XY mouse model may be a valuable tool for studying specific events in the degeneration of the neocortex, and may suggest new avenues for therapeutic intervention.

Looking for trouble: revenge-planning and preattentive vigilance for angry facial expressions.

Revenge-planning refers to individual differences in the tendency to actively seek out hostile confrontations with others. Building on past theory, we hypothesized that revenge-planning would be related to preattentive vigilance for angry facial expressions. By being vigilant for such expressions, individuals could more readily notice and prepare to confront social challenges. We conducted 2 studies to test this prediction. Across studies, results indicated that participants high in revenge-planning had significantly longer color-naming latencies for masked angry expressions presented in a subliminal Stroop task, regardless of whether the expression was presented inside or outside participants' attentional focus. This phenomenon was specific to revenge-planning and did not extend to the related construct of angry rumination. Such results suggest that preattentive vigilance for angry expressions supports a confrontational social style in which a person actively seeks out hostile social encounters.

In vivo characterization of a bigenic fluorescent mouse model of Alzheimer's disease with neurodegeneration.

The loss of cognitive function in Alzheimer's disease (AD) patients is strongly correlated with the loss of neurons in various regions of the brain. We have created a new fluorescent bigenic mouse model of AD by crossing "H-line" yellow fluorescent protein (YFP) mice with the 5xFAD mouse model, which we call the 5XY mouse model. The 5xFAD mouse has been shown to have significant loss of L5 pyramidal neurons by 12 months of age. These neurons are transgenically labeled with YFP in the 5XY mouse, which enable longitudinal imaging of structural changes. In the 5XY mice, we observed an appearance of axonal dystrophies, with two distinct morphologies in the early stages of the disease progression. Simple swelling dystrophies are transient in nature and are not directly associated with amyloid plaques. Rosette dystrophies are more complex structures that remained stable throughout all imaging sessions, and always surrounded an amyloid plaque. Plaque growth was followed over 4 weeks, and significant growth was seen between weekly imaging sessions. In addition to axonal dystrophy appearance and plaque growth, we were able to follow spine stability in 4-month old 5XY mice, which revealed no significant loss of spines. 5XY mice also showed a striking shrinkage of the neocortex at older ages (12-14 months). The 5XY mouse model may be a valuable tool for studying specific events in the degeneration of the neocortex, and may suggest new avenues for therapeutic intervention.

Photochemically initiated intracellular astrocytic calcium waves in living mice using two-photon uncaging of IP(3).

We have developed a caged IP(3) analogue for two-photon photolysis in living animals. This probe is a cell permeable version and was coloaded with a fluorescent Ca(2+) dye into astrocytes in layer 1 of the somatosensory cortex of anesthetized mice. Two-photon irradiation of single cells at 720 nm produced rapid and robust increases in intracellular Ca(2+) concentrations monitored using two-photon microscopy at 950 nm. The photoevoked intracellular Ca(2+) waves were similar in magnitude to intrinsic signals in wild type mice. These waves did not propagate to other cells beyond the targeted astrocyte. In contrast, we observed intercellular astrocytic Ca(2+) waves in two mouse models of familial Alzheimer's disease. These data suggest that Alzheimer's might perturb gliotransmission but not IP(3) signaling per se in mouse models of the disease.