The majority of current neurovascular research involves monitoring neurovascular parameters from animals housed in a standard cage, which is clearly not an environment that mimics the human condition. Indeed, previous findings from our lab regarding large scale plasticity in sensory cortex of rats demonstrated that activity-dependent plasticity of whiskers cortical representations in uncaged rats shows opposite direction and magnitude compared to activity-dependent plasticity in caged rodents. These findings suggest that the large- scale plasticity seen in uncaged rats should also be accompanied by large scale supportive neurovascular plasticity. We propose to study such cortical neurovascular plasticity by using our ?naturalistic habitat?. The naturalistic habitat is an environment which mimics the natural world of rats within the confines of a vivarium by promoting free movement, burrowing, foraging and continuous interactions with conspecifics, which led to major plasticity of cortical maps. To study how transfer to the naturalistic habitat for one and six months modifies the neurovascular system, we propose to employ a battery of vascular imaging and neuronal recording techniques within the same rat and compare the findings with rats that stayed for the same period in standard cages. Based on our previous plasticity results, our hypothesis is that rats that stay in the naturalistic habitat will have a much more efficient neurovascular system compared to the standard cage rats, and that longer duration in the naturalistic habitat will entail a progressively more efficient system. In addition, in order to further improve our animal model, we propose to divide our proposed studies into two major parts. In the first part all imaging and recording studies will be performed in anesthetized rats. In the second part all proposed studies will be performed on awake, head fixed rats. This design will achieve (1) further optimizing our rat model to the human condition, and (2) ability to study the effects of anesthesia on our neurovascular model. Successful completion of our combined aims could have major implications for the appropriateness of caged animals as a model of healthy human neurovascular system and therefore successful completion of our proposal could lead to a more optimal animal model that, in turn, could lead to better success of future translational neurovascular research in healthy rodent models and in rodent models of pathological neurovascular diseases.
A problem in neurovascular research is that animal models are housed in standard cages, a structural, motor, sensory and socially impoverished environment that is not representative of human environments. Using a battery of advanced blood flow imaging and neuronal recordings techniques, we propose to study the differences between living in a standard cage or living in our ?naturalistic habitat? ? an environment that imitates the natural rodent world within the confines of a vivarium. To further optimize our animal model to be more relevant to humans, we propose to study the neurovascular system in awake animals, and in addition reveal the differences between anesthetized and awake animals. Collectively our studies aim to reach for the optimal animal model for translational neurovascular research.
