Behavioral measurements of motor readiness in mice.

Motor planning facilitates rapid and precise execution of volitional movements. Although motor planning has been classically studied in humans and monkeys, the mouse has become an increasingly popular model system to study neural mechanisms of motor planning. It remains yet untested whether mice and primates share common behavioral features of motor planning. We combined videography and a delayed response task paradigm in an autonomous behavioral system to measure motor planning in non-body-restrained mice. Motor planning resulted in both reaction time (RT) savings and increased movement accuracy, replicating classic effects in primates. We found that motor planning was reflected in task-relevant body features. Both the specific actions prepared and the degree of motor readiness could be read out online during motor planning. The online readout further revealed behavioral evidence of simultaneous preparation for multiple actions under uncertain conditions. These results validate the mouse as a model to study motor planning, demonstrate body feature movements as a powerful real-time readout of motor readiness, and offer behavioral evidence that motor planning can be a parallel process that permits rapid selection of multiple prepared actions.

Vaccine-linked chemotherapy improves cardiac structure and function in a mouse model of chronic Chagas disease.

Introduction: Chagas disease, caused by chronic infection with the protozoan parasite Trypanosoma cruzi, affects 6-7 million people worldwide. The major clinical manifestation of Chagas disease is chronic Chagasic cardiomyopathy (CCC), which encompasses a spectrum of symptoms including arrhythmias, hypertrophy, dilated cardiomyopathy, heart failure, and sudden death. Current treatment is limited to two antiparasitic drugs, benznidazole (BNZ) and nifurtimox, but both have limited efficacy to halt the progression of CCC. We developed a vaccine-linked chemotherapy strategy using our vaccine consisting of recombinant Tc24-C4 protein and a TLR-4 agonist adjuvant in a stable squalene emulsion, in combination with low dose benznidazole treatment. We previously demonstrated in acute infection models that this strategy parasite specific immune responses, and reduced parasite burdens and cardiac pathology. Here, we tested our vaccine-linked chemotherapy strategy in a mouse model of chronic T. cruzi infection to evaluate the effect on cardiac function. Methods: Female BALB/c mice infected with 500 blood form T. cruzi H1 strain trypomastigotes were treated beginning 70 days after infection with a low dose of BNZ and either low or high dose of vaccine, in both sequential and concurrent treatments streams. Control mice were untreated, or administered only one treatment. Cardiac health was monitored throughout the course of treatment by echocardiography and electrocardiograms. Approximately 8 months after infection, endpoint histopathology was performed to measure cardiac fibrosis and cellular infiltration. Results: Vaccine-linked chemotherapy improved cardiac function as evidenced by amelioration of altered left ventricular wall thickness, left ventricular diameter, as well as ejection fraction and fractional shortening by approximately 4 months of infection, corresponding to two months after treatment was initiated. At study endpoint, vaccine-linked chemotherapy reduced cardiac cellular infiltration, and induced significantly increased antigen specific IFN-γ and IL-10 release from splenocytes, as well as a trend toward increased IL-17A. Discussion: These data suggest that vaccine-linked chemotherapy ameliorates changes in cardiac structure and function induced by infection with T. cruzi. Importantly, similar to our acute model, the vaccine-linked chemotherapy strategy induced durable antigen specific immune responses, suggesting the potential for a long lasting protective effect. Future studies will evaluate additional treatments that can further improve cardiac function during chronic infection.

Behavioral measurements of motor readiness in mice.

Motor planning facilitates rapid and precise execution of volitional movements. Although motor planning has been classically studied in humans and monkeys, the mouse has become an increasingly popular model system to study neural mechanisms of motor planning. It remains yet untested whether mice and primates share common behavioral features of motor planning. We combined videography and a delayed response task paradigm in an autonomous behavioral system to measure motor planning in non-body- restrained mice. Motor planning resulted in both reaction time savings and increased movement accuracy, replicating classic effects in primates. We found that motor planning was reflected in task-relevant body features. Both the specific actions prepared and the degree of motor readiness could be read out online during motor planning. The online readout further revealed behavioral evidence of simultaneous preparation for multiple actions under uncertain conditions. These results validate the mouse as a model to study motor planning, demonstrate body feature movements as a powerful real-time readout of motor readiness, and offer behavioral evidence that motor planning can be a parallel process that permits rapid selection of multiple prepared actions.