Unpredictable Mixed-Valence Outcomes Induce a Chronic and Reversible Generalized Anxiety-like Phenotype in Male Mice.

Background: Clinical anxiety is a generalized state characterized by feelings of apprehensive expectation and is distinct from momentary responses such as fear or stress. In contrast, most laboratory tests of anxiety focus on acute responses to momentary stressors.

Methods: Apprehensive expectation was induced by subjecting mice (for 18 days) to manipulations in which a running response (experiment 1) or a conditioned stimulus (experiment 2) were unpredictably paired with reward (food) or punishment (footshock).

A Chronic Increase in Blood-Brain Barrier Permeability Facilitates Intraneuronal Deposition of Exogenous Bloodborne Amyloid-Beta1-42 Peptide in the Brain and Leads to Alzheimer's Disease-Relevant Cognitive Changes in a Mouse Model.

Background: Increased blood-brain barrier (BBB) permeability and amyloid-β (Aβ) peptides (especially Aβ1-42) (Aβ42) have been linked to Alzheimer's disease (AD) pathogenesis, but the nature of their involvement in AD-related neuropathological changes leading to cognitive changes remains poorly understood.

Objective: To test the hypothesis that chronic extravasation of bloodborne Aβ42 peptide and brain-reactive autoantibodies and their entry into the brain parenchyma via a permeable BBB contribute to AD-related pathological changes and cognitive changes in a mouse model.

Methods: The BBB was rendered chronically permeable through repeated injections of Pertussis toxin (PT), and soluble monomeric, fluorescein isothiocyanate (FITC)-labeled or unlabeled Aβ42 was injected into the tail-vein of 10-month-old male CD1 mice at designated intervals spanning ∼3 months.

Negative attributes of mixed-valence memories strengthen over long retention intervals and the degree of enhancement is predicted by individual differences in state anxiety.

Memories are multifaceted and can simultaneously contain positive and negative attributes. Here, we report that negative attributes of a mixed-valence memory dominate long-term recall. To induce a mixed-valence memory, running responses were randomly reinforced with either food (∼83% of trials) or footshock (∼17% of trials), or a noise conditioned stimulus (CS) was followed randomly with either food (∼80% of trials) or footshock (∼20% of trials).

A multi-faceted role of dual-state dopamine signaling in working memory, attentional control, and intelligence.

Genetic evidence strongly suggests that individual differences in intelligence will not be reducible to a single dominant cause. However, of those variations/changes may be traced to tractable, cohesive mechanisms. One such mechanism may be the balance of dopamine D1 (DR) and D2 (DR) receptors, which regulate intrinsic currents and synaptic transmission in frontal cortical regions.

Déjà vu All Over Again: A Unitary Biological Mechanism for Intelligence Is (Probably) Untenable.

Nearly a century ago, Spearman proposed that "specific factors can be regarded as the 'nuts and bolts' of cognitive performance…, while the general factor is the mental energy available to power the specific engines". Geary (2018; 2019) takes Spearman's analogy of "mental energy" quite literally and doubles-down on the notion by proposing that a unitary energy source, the mitochondria, explains variations in both cognitive function and health-related outcomes. This idea is reminiscent of many earlier attempts to describe a low-level biological determinant of general intelligence.