Familiarity with social sounds alters c-Fos expression in auditory cortex and interacts with estradiol in locus coeruleus

Abstract

When a social sound category initially gains behavioral significance to an animal, plasticity events presumably enhance the ability to recognize that sound category in the future. In the context of learning natural social stimuli, neuromodulators such as norepinephrine and estrogen have been associated with experience-dependent plasticity and processing of newly salient social cues, yet continued plasticity once stimuli are familiar could disrupt the stability of sensorineural representations. Here we employed a maternal mouse model of natural sensory cortical plasticity for infant vocalizations to ask whether the engagement of the noradrenergic locus coeruleus (LC) by the playback of pup-calls is affected by either prior experience with the sounds or estrogen availability, using a well-studied cellular activity and plasticity marker, the immediate early gene c-Fos. We counted call-induced c-Fos immunoreactive (c-Fos-IR) cells in both LC and physiologically validated fields within the auditory cortex (AC) of estradiol or blank-implanted virgin female mice with either 0 or 5-days prior experience caring for vocalizing pups. Estradiol and pup experience interacted both in the induction of c-Fos-IR in the LC, as well as in behavioral measures of locomotion during playback, consistent with the neuromodulatory center's activity being an online reflection of both hormonal and experience-dependent influences on arousal. Throughout core AC, as well as in a high frequency sub-region of AC and in secondary AC, a main effect of pup experience was to reduce call-induced c-Fos-IR, irrespective of estradiol availability. This is consistent with the hypothesis that sound familiarity leads to less c-Fos-mediated plasticity, and less disrupted sensory representations of a meaningful call category. Taken together, our data support the view that any coupling between these sensory and neuromodulatory areas is situationally dependent, and their engagement depends differentially on both internal state factors like hormones and external state factors like prior experience.

Social isolation improves the performance of rodents in a novel cognitive flexibility task

“…Thus, it is conceivable that inhibitory control deficits might be the neural basis for increases in novel exploration and subsequently for the improvement in unconstrained flexibility. Moreover, as gregarious animals, mice normally live in groups and are adapted to supporting and interacting with conspecific individuals [1–3, 46, 47]. However, isolation rearing would interrupt these relationships and individual mice would be forced to navigate their the complex surroundings and survival problems alone, which may increase investigation motivation to compensate for the absence of social support [12, 41].…”

Silence, Solitude, and Serotonin: Neural Mechanisms Linking Hearing Loss and Social Isolation

“…Multiple centralized neuromodulatory systems widely innervate sensory and integrative brain regions, and respond to changes in environmental conditions [ 64 ]. For example, noradrenergic neurons within the locus coeruleus are sensitive to behaviorally important information, such as social context or stress, are affected by social experience, influence connectivity in neural networks related to salience and affect, and alter performance on sensory and cognitive tasks [ 201 , 202 , 203 , 204 , 205 , 206 ]. These kinds of similarities in some of the aspects of how serotonergic, noradrenergic, and other neurochemical systems work have led to the view that these systems may cooperate in regulating integrative neural functions [ 74 , 207 ].…”

Capacities and neural mechanisms for auditory statistical learning across species

“…Importantly, it has recently been shown that oxytocin release during repetitive exposure to pup vocalizations induced long term cortical changes in non-maternal mice, such that cortical responses to calls were highly temporally precise, similar to the maternal brain (Marlin et al 2015). Finally, there is evidence that pup vocalizations activate the locus coeruleus, a subcortical nucleus synthesizing norepinephrine, in virgin and maternal mice (Moreno et al 2018). This demonstrates that vocalizations may themselves be able to activate neuromodulatory centers for the induction of plasticity, possibly increasing a dam's sensitivity to high-probability features defining stimulus category in the absence of external factors (Moreno et al 2018).…”

“…Finally, there is evidence that pup vocalizations activate the locus coeruleus, a subcortical nucleus synthesizing norepinephrine, in virgin and maternal mice (Moreno et al 2018). This demonstrates that vocalizations may themselves be able to activate neuromodulatory centers for the induction of plasticity, possibly increasing a dam's sensitivity to high-probability features defining stimulus category in the absence of external factors (Moreno et al 2018).…”