Enhanced fear expression in a psychopathological mouse model of trait anxiety: pharmacological interventions.

The propensity to develop an anxiety disorder is thought to be determined by genetic and environmental factors. Here we investigated the relationship between a genetic predisposition to trait anxiety and experience-based learned fear in a psychopathological mouse model. Male CD-1 mice selectively bred for either high (HAB), or normal (NAB) anxiety-related behaviour on the elevated plus maze were subjected to classical fear conditioning. During conditioning both mouse lines showed increased fear responses as assessed by freezing behaviour. However, 24 h later, HAB mice displayed more pronounced conditioned responses to both a contextual or cued stimulus when compared with NAB mice. Interestingly, 6 h and already 1 h after fear conditioning, freezing levels were high in HAB mice but not in NAB mice. These results suggest that trait anxiety determines stronger fear memory and/or a weaker ability to inhibit fear responses in the HAB line. The enhanced fear response of HAB mice was attenuated by treatment with either the α(2,3,5)-subunit selective benzodiazepine partial agonist L-838,417, corticosterone or the selective neurokinin-1 receptor antagonist L-822,429. Overall, the HAB mouse line may represent an interesting model (i) for identifying biological factors underlying misguided conditioned fear responses and (ii) for studying novel anxiolytic pharmacotherapies for patients with fear-associated disorders, including post-traumatic stress disorder and phobias.

Model-based development of neural prostheses for movement.

Neural prostheses for restoration of limb movement in paralyzed and amputee patients tend to be complex systems. Subjective intuition and trial-and-error approaches have been applied to the design and clinical fitting of simple systems with limited functionality. These approaches are time consuming, difficult to apply in larger scale, and not applicable to limbs under development with more anthropomorphic motion and actuation. The field of neural prosthetics is in need of more systematic methods, including tools that will allow users to develop accurate models of neural prostheses and simulate their behavior under various conditions before actual manufacturing or clinical application. Such virtual prototyping would provide an efficient and safe test-bed for narrowing the design choices and tuning the control parameters before actual clinical application. We describe a software environment that we have developed to facilitate the construction and modification of accurate mathematical models of paralyzed and prosthetic limbs and simulate their movement under various neural control strategies. These simulations can be run in real time with a stereoscopic display to enable design engineers and prospective users to evaluate a candidate neural prosthetic system and learn to operate it before actually receiving it.