ABSTRACT
Adult rats emit ultrasonic vocalizations (USVs) related to their affective states, potentially providing information about their subjective experiences during behavioral neuroscience experiments. If so, USVs might provide an important link between invasive animal preclinical studies and human studies in which subjective states can be readily queried. Here, we induced USVs in male and female Long Evans rats using acute amphetamine (2 mg/kg), and asked how reversibly inhibiting nucleus accumbens neurons using designer receptors exclusively activated by designer drugs (DREADDs) impacts USV production. We analyzed USV characteristics using "Deepsqueak" software, and manually categorized detected calls into four previously defined subtypes. We found that systemic administration of the DREADD agonist clozapine-n-oxide, relative to vehicle in the same rats, suppressed the number of frequency-modulated and trill-containing USVs without impacting high frequency, unmodulated (flat) USVs, nor the small number of low-frequency USVs observed. Using chemogenetics, these results thus confirm that nucleus accumbens neurons are essential for production of amphetamine-induced frequency-modulated USVs. They also support the premise of further investigating the characteristics and subcategories of these calls as a window into the subjective effects of neural manipulations, with potential future clinical applications.
ABSTRACT
Alzheimer's disease (AD) is characterized by dysfunction in cognitive and noncognitive domains with clinical diagnosis based on multiple neuropsychological tests. Here, we evaluated cognitive and noncognitive behaviors in 2 age cohorts (8 and 14 months at the start of the study) of APPSwe/PS1dE9 transgenic mice that model AD-like amyloidosis. We used a battery of tests that included fear-conditioned context and tone memories, swimming activity, and orientation to a proximal cue in a visible platform water maze test and burrowing and nest building activity. To compare the performance of mice across all tests, we used z-score normalization of data. The analyses revealed that the behavior of the transgenic mice was significantly compromised in cognitive as well as in noncognitive domains. Combining scores across multiple behavioral tests produced an integrated index characterizing the overall phenotypic abnormality in this model of AD-like amyloidosis. Assessing multiple behavioral domains provides a broader view of the breadth of impairments in multiple behavioral systems. Greater implementation of such approaches could enable reliable and clinically predictive evaluation of therapeutics in mouse models of amyloidosis.
