Ultrasonic vocalization changes and FOXP2 expression after experimental stroke

Abstract

Speech impairments affect one in four stroke survivors. However, animal models of post-ischemic vocalization deficits are limited. Male mice vocalize at ultrasonic frequencies when exposed to an estrous female mouse. In this study we assessed vocalization patterns and quantity in male mice after cerebral ischemia. FOXP2, a gene associated with verbal dyspraxia in humans, with known roles in neurogenesis and synaptic plasticity, was also examined after injury. Using a transient middle cerebral artery occlusion (MCAO) model, we assessed correlates of vocal impairment at several time-points after stroke. Further, to identify possible lateralization of vocalization deficits induced by left and right hemispheric strokes were compared. Significant differences in vocalization quantity were observed between stroke and sham animals that persisted for a month after injury. Injury to the left hemisphere reduced early vocalizations more profoundly than those to the right hemisphere. Nuclear expression of Foxp2 was elevated early after stroke (at 6 hours), but significantly decreased 24 hours after injury in both the nucleus and the cytoplasm. Neuronal Foxp2 expression increased in stroke mice compared to sham animals 4 weeks after injury. This study demonstrates that quantifiable deficits in ultrasonic vocalizations (USVs) are seen after stroke. USV may be a useful tool to assess chronic behavioral recovery in murine models of stroke.

Right lateralized posterior parietal theta-gamma coupling during sustained attention in mice

“…Lateralization of sustained attention toward the right PPC has been 3 supported by great deal of evidence from lesion and functional imaging studies in humans (Petersen and 4 Posner, 2012;Posner and Petersen, 1990); however, the dominance of the right PPC for sustained 5 attention in rodents, to our knowledge, has not previously been recognized. Our findings are consistent 6 with prior studies showing lateralization of other higher-order cortical function in mice as seen in 7 humans (Duboc et al, 2015), including right hippocampal dominance for visuospatial memory 8 (Shinohara et al, 2012) and left hemispheric dominance for vocalization expression and response 9 (Doran et al, 2015;Ehret, 1987;Levy et al, 2019). Altogether, our results join a growing body of data 10 positioning mice as a potential translational model of some higher order cognitive functions.…”

EMMPRIN/CD147 plays a detrimental role in clinical and experimental ischemic stroke

“…Thirty-micron sections were slide mounted and incubated in Normal Goat Serum (Sigma) with 0.15% TritonX in PBS as previously described [50]. Sections were incubated overnight with rat anti-CD147 (1:200, ABDserotec), and then incubated for 60 minutes with anti-host antibody conjugated with a fluorophore (1:1000), DAPI nuclear stain solution (1:1000; Invitrogen), and GFAP primary conjugated antibody (1:200, Invitrogen) as previously described in [51].…”

Mouse and rat ultrasonic vocalizations in neuroscience and neuropharmacology: State of the art and future applications

“…USVs are also studied in non‐genetic murine models, for instance, those of cerebral ischemia, as a behavioral marker of post‐traumatic recovery; indeed, speech impairments are often negative consequences of an ischemic event. Using the transient middle cerebral artery occlusion (MCAO) murine model, Doran et al (2015) demonstrated that injury to the left hemisphere reduced early vocalizations more profoundly than those to the right hemisphere. Also, neonatal hypoxic ischemia encephalopathy (HIE) leads to major deficits in language development; hypoxic ischemia induced by right common carotid artery transient ligation at PND 10 provokes a significant reduction in USV emission (Doran et al, 2019).…”