Leveraging individual differences in cue-reward learning to investigate the psychological and neural basis of shared psychiatric symptomatology: The sign-tracker/goal-tracker model.

In our modern environment, we are bombarded with stimuli or cues that exert significant influence over our actions. The extent to which such cues attain control over or disrupt goal-directed behavior is dependent on several factors, including one's inherent tendencies. Using a rodent model, we have shown that individuals vary in the value they place on stimuli associated with reward. Some individuals, termed "goal-trackers," primarily attribute predictive value to reward cues, whereas others, termed "sign-trackers," attribute predictive and incentive value. Thus, for sign-trackers, the reward cue is transformed into an incentive stimulus that is capable of eliciting maladaptive behaviors. The sign-tracker/goal-tracker animal model has allowed us to refine our understanding of behavioral and computational theories related to reward learning and to parse the underlying neural processes. Further, the neurobehavioral profile of sign-trackers is relevant to several psychiatric disorders, including substance use disorder, impulse control disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, and posttraumatic stress disorder. This model, therefore, can advance our understanding of the psychological and neurobiological mechanisms that contribute to individual differences in vulnerability to psychopathology. Notably, initial attempts at translation-capturing individual variability in the propensity to sign-track in humans-have been promising and in line with what we have learned from the animal model. In this review, we highlight the pivotal role played by the sign-tracker/goal-tracker animal model in enriching our understanding of the psychological and neural basis of motivated behavior and psychiatric symptomatology. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Neuromodulation and the toolkit for behavioural evolution: can ecdysis shed light on an old problem?

The geneticist Thomas Dobzhansky famously declared: 'Nothing in biology makes sense except in the light of evolution'. A key evolutionary adaptation of Metazoa is directed movement, which has been elaborated into a spectacularly varied number of behaviours in animal clades. The mechanisms by which animal behaviours have evolved, however, remain unresolved. This is due, in part, to the indirect control of behaviour by the genome, which provides the components for both building and operating the brain circuits that generate behaviour. These brain circuits are adapted to respond flexibly to environmental contingencies and physiological needs and can change as a function of experience. The resulting plasticity of behavioural expression makes it difficult to characterize homologous elements of behaviour and to track their evolution. Here, we evaluate progress in identifying the genetic substrates of behavioural evolution and suggest that examining adaptive changes in neuromodulatory signalling may be a particularly productive focus for future studies. We propose that the behavioural sequences used by ecdysozoans to moult are an attractive model for studying the role of neuromodulation in behavioural evolution.

Large-scale identification of human cerebrovascular proteins: Inter-tissue and intracerebral vascular protein diversity.

The human cerebrovascular system is responsible for regulating demand-dependent perfusion and maintaining the blood-brain barrier (BBB). In addition, defects in the human cerebrovasculature lead to stroke, intracerebral hemorrhage, vascular malformations, and vascular cognitive impairment. The objective of this study was to discover new proteins of the human cerebrovascular system using expression data from the Human Protein Atlas, a large-scale project which allows public access to immunohistochemical analysis of human tissues. We screened 20,158 proteins in the HPA and identified 346 expression patterns correlating to blood vessels in human brain. Independent experiments showed that 51/52 of these distributions could be experimentally replicated across different brain samples. Some proteins (40%) demonstrated endothelial cell (EC)-enriched expression, while others were expressed primarily in vascular smooth muscle cells (VSMC; 18%); 39% of these proteins were expressed in both cell types. Most brain EC markers were tissue oligospecific; that is, they were expressed in endothelia in an average of 4.8 out of 9 organs examined. Although most markers expressed in endothelial cells of the brain were present in all cerebral capillaries, a significant number (21%) were expressed only in a fraction of brain capillaries within each brain sample. Among proteins found in cerebral VSMC, virtually all were also expressed in peripheral VSMC and in non-vascular smooth muscle cells (SMC). Only one was potentially brain specific: VHL (Von Hippel-Lindau tumor suppressor). HRC (histidine rich calcium binding protein) and VHL were restricted to VSMC and not found in non-vascular tissues such as uterus or gut. In conclusion, we define a set of brain vascular proteins that could be relevant to understanding the unique physiology and pathophysiology of the human cerebrovasculature. This set of proteins defines inter-organ molecular differences in the vasculature and confirms the broad heterogeneity of vascular cells within the brain.