Vocal Communication During Early Mother-Infant Interaction: Studies Using the Wistar-Kyoto Rat Model of Depression

Postpartum depression is a serious psychiatric condition that has deleterious effects on the mother and poses a risk for the mother-infant relationship and ultimately the infant’s development. Maternal anhedonia and social communication deficits are two major clinical features central to postpartum depression that likely contribute to deficits in parenting. The present study used Wistar-Kyoto (WKY) mother rats, an animal model of depression which we have developed to examine the postpartum disorder, to investigate the relationship between maternal anhedonia, social communication deficits and parenting disturbances. Rats produce ultrasonic vocalizations (USVs) in different social contexts, and USVs are becoming an increasingly valuable assay for behavioral phenotyping. Alterations of the ultrasound patterns have been reported in several models of neuropsychiatric disorders, including those associated with communicative/social deficits, and can also provide reliable insight into the affective state of the mother rat during social interactions with her litter. In the first study, WKY and control Sprague-Dawley (SD) postpartum females were examined for their affective responses to social cues from pups, as measured by their ultrasonic vocalizations (USVs) during a 30-minute maternal behavior test following 20 minutes of mother-litter separation. Total number of calls, acoustic frequency and duration of calls, and individual USV profiles were analyzed in conjunction with maternal behavior. Both WKY and SD mothers predominantly produced ~50 kHz USVs when interacting with the pups in the maternal behavior test. WKY mothers emitted more trill-type USVs as is compared with SD mothers. Similarly, WKY mothers exhibited substantial disturbances in theirmaternal behavior. A second experiment evaluated the therapeutic efficacy of adenosine A2A receptor antagonism as a novel treatment strategy for postpartum depression. Emerging evidence indicates that the neuromodulator adenosine, particularly through actions on adenosine A2A receptors, modulates behavioral functions associated with the mesocorticolimbic DA system, including cognitive and motivational processes. Results indicate that acute MSX-3 administration did not attenuate the parenting disturbances of WKY or affect the USV emissions of either strain. Taken together, these results provide evidence for the presence of maternal USVs during motherlitter interactions, and further suggest that variations in USVs produced by mothers during social interaction with their pups may function as an index of their affect. Rat USVs may be used to study the neurobiological mechanisms underlying maternal affect in animal models of postpartum disorders

Repeated mild traumatic brain injury triggers pathology in asymptomatic C9ORF72 transgenic mice

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are fatal neurodegenerative diseases that represent ends of the spectrum of a single disease. The most common genetic cause of FTD and ALS is a hexanucleotide repeat expansion in the C9orf72 gene. Although epidemiological data suggest that traumatic brain injury (TBI) represents a risk factor for FTD and ALS, its role in exacerbating disease onset and course remains unclear. To explore the interplay between traumatic brain injury and genetic risk in the induction of FTD/ALS pathology we combined a mild repetitive traumatic brain injury paradigm with an established bacterial artificial chromosome transgenic C9orf72 (C9BAC) mouse model without an overt motor phenotype or neurodegeneration. We assessed 8–10 week-old littermate C9BACtg/tg (n = 21), C9BACtg/− (n = 20) and non-transgenic (n = 21) mice of both sexes for the presence of behavioural deficits and cerebral histopathology at 12 months after repetitive TBI. Repetitive TBI did not affect body weight gain, general neurological deficit severity, nor survival over the 12-month observation period and there was no difference in rotarod performance, object recognition, social interaction and acoustic characteristics of ultrasonic vocalizations of C9BAC mice subjected to repetitive TBI versus sham injury. However, we found that repetitive TBI increased the time to the return of the righting reflex, reduced grip force, altered sociability behaviours and attenuated ultrasonic call emissions during social interactions in C9BAC mice. Strikingly, we found that repetitive TBI caused widespread microglial activation and reduced neuronal density that was associated with loss of histological markers of axonal and synaptic integrity as well as profound neuronal transactive response DNA binding protein 43 kDa mislocalization in the cerebral cortex of C9BAC mice at 12 months; this was not observed in non-transgenic repetitive TBI and C9BAC sham mice. Our data indicate that repetitive TBI can be an environmental risk factor that is sufficient to trigger FTD/ALS-associated neuropathology and behavioural deficits, but not paralysis, in mice carrying a C9orf72 hexanucleotide repeat expansion