Increased sensitivity in detection of deficits following two commonly used animal models of stroke.

Stroke is a leading cause of death and disability in the United States. Most strokes are ischemic, resulting in both cognitive and motor impairments. Animal models of ischemic stroke such as the distal middle cerebral artery occlusion (dMCAO) and photothrombotic stroke (PTS) procedures have become invaluable tools, with their own advantages and disadvantages. The dMCAO model is clinically relevant as it occludes the artery most affected in humans, but yields variability in the infarct location as well as the behavioral and cognitive phenotypes disrupted. The PTS model has the advantage of allowing for targeted location of infarct, but is less clinically relevant. The present study evaluates phenotype disruption over time in mice subjected to either dMCAO, PTS, or a sham surgery. Post-surgery, animals were tested over 28 days on standard motor tasks (grid walk, cylinder, tapered beam, and rotating beam), as well as a novel odor-based operant task; the 5:1 Odor Discrimination Task (ODT). Results demonstrate a significantly greater disturbance of motor control with PTS as compared with Sham and dMCAO. Disruption of the PTS group was detected up to 28 days post-stroke on the grid walk, and up to 7 days on the rotating and tapered beam tasks. PTS also led to significant short-term disruption of ODT performance (1-day post-surgery), exclusively in males, which appeared to be driven by motoric disruption of the lick response. Together, this data provides critical insights into the selection and optimization of animal models for ischemic stroke research. Notably, the PTS procedure was best suited for producing disruptions of motor behavior that can be detected with common behavioral assays and are relatively enduring, as is observed in human stroke.

Olfactory Dysfunction in Schizophrenia: Evaluating Olfactory Abilities Across Species.

Though understudied relative to perturbations in the auditory and visual domains, olfactory dysfunction is a common symptom of schizophrenia. Over the past two decades, the availability of standardized assessments to quantify human olfactory abilities, and enhance understanding of the neurophysiology supporting olfaction, has increased, enabling a more thorough characterization of these deficits. In contrast to other psychiatric conditions for which olfactory dysfunction has been observed (e.g., major depressive disorder, bipolar disorder, Alzheimer's disease), the impairments observed in schizophrenia are particularly global and profound. At this level, such deficits in olfactory abilities likely impact the enjoyment of food, detection of environmental hazards, and influence social relationships. More broadly, the study of olfactory phenotypes in schizophrenia presents new avenues for detection of those at-risk for the condition, identification of therapeutic targets for treatment development, and for the characterization of novel animal models relevant to schizophrenia and psychosis. This review will consider the olfactory performance of individuals with schizophrenia in domains for which standardized assessments are available (odor sensitivity, discrimination, identification, and memory). Paradigms available for assessing these abilities in rodents will also be discussed with the aim of facilitating translation. Thus, future studies will be able to include cross-species translation of mechanisms relevant to olfactory function and cognition, what has gone awry in the disease state, and test potential therapeutics.