Scientific Understanding of Consciousness
Oxytocin Balances Cortical Inhibition with Excitation
Nature 520, 499–504 (23 April 2015)
Oxytocin enables maternal behaviour by balancing cortical inhibition
Bianca J. Marlin, et.al.
Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA
Neuroscience Institute, New York University School of Medicine, New York, New York 10016, USA
Department of Otolaryngology, New York University School of Medicine, New York, New York 10016, USA
Department of Neuroscience and Physiology, New York University School of Medicine, New York, New York 10016, USA
Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA
Department of Psychiatry, New York University School of Medicine, New York, New York 10016, USA
Center for Neural Science, New York University, New York, New York 10003, USA
Oxytocin neuropeptide neuromodulator hormone is important for social interactions and maternal behaviour. However, little is known about when, where and how oxytocin modulates neural circuits to improve social cognition. Here we show how oxytocin enables pup retrieval behaviour in female mice by enhancing auditory cortical pup call responses. Retrieval behaviour required the left but not right auditory cortex, was accelerated by oxytocin in the left auditory cortex, and oxytocin receptors were preferentially expressed in the left auditory cortex. Neural responses to pup calls were lateralized, with co-tuned and temporally precise excitatory and inhibitory responses in the left cortex of maternal but not pup-naive adults. Finally, pairing calls with oxytocin enhanced responses by balancing the magnitude and timing of inhibition with excitation. Our results describe fundamental synaptic mechanisms by which oxytocin increases the salience of acoustic social stimuli. Furthermore, oxytocin-induced plasticity provides a biological basis for lateralization of auditory cortical processing.
The neuropeptide oxytocin controls social behaviours such as pair bond formation, mating and parenting. Oxytocin is synthesized in the paraventricular nucleus (PVN) and supraoptic nucleus of the hypothalamus, and binds to a G-protein-coupled receptor with a single isoform. Peripheral release of oxytocin is important for parturition and lactation, whereas central release of oxytocin appears to have cognitive effects including increased interpersonal trust and enhanced salience of socially relevant sensory input. However, it remains unclear which neurons express oxytocin receptors, or how oxytocin interacts with experience to modify neural circuits and increase the salience of social information.
Here we examine how oxytocin is involved in pup retrieval, an important form of mammalian social behaviour. Mouse pups emit ultrasonic distress calls when separated from the nest, which experienced mothers (known as dams) use to locate and retrieve isolated pups. This behaviour relies on the auditory system, as pup calls played by speakers attract maternal animals. Physiologically, neural responses to pup calls in the mouse auditory cortex differ between dams and virgin females, with higher signal-to-noise ratios in maternal mice. Correspondingly, most inexperienced animals do not initially retrieve pups. Intriguingly, some virgin female rodents start retrieving pups after being co-housed with dam and pups or after central administration of oxytocin. An ethologically important form of plasticity in the auditory cortex might therefore be enabled by oxytocin in maternal animals, allowing them to recognize the behavioural significance of infant distress calls. Here we aim to show how these neural changes occur, and what role oxytocin has in experience-dependent pup retrieval by virgins.
Our results demonstrate a remarkable degree of functional lateralization in the mammalian brain and provide a molecular basis for this phenomenon. The left auditory cortex is specialized for recognizing the behavioural significance of infant distress calls and required for maternal retrieval of isolated pups. This is markedly similar to the asymmetry of speech processing in human temporal lobe, and supports earlier behavioural observations of auditory lateralization in maternal mice. We generated an antibody to the mouse oxytocin receptor, OXTR-2, and found more receptor expression in the left auditory cortex. A dedicated neural circuit, enriched for oxytocin receptors, might therefore be specialized for processing important social signals such as pup distress calls. This specialization would allow maternal animals to attend to their young and return pups to the nest rapidly and reliably. Furthermore, given the importance of olfactory signals in social behaviours including pup retrieval, it is likely that oxytocin also enhances olfaction in combination with other cues (for example, pup calls) to improve parenting behaviour synergistically.
Although many aspects of mammalian maternal behaviour may be innate, recognition of the behavioural importance of pup calls depends on experience. Several studies highlight differences between AI responses in maternal and pup-naive female mice. In particular, pup call responses have been found to be less reliable in pup-naive virgins. Our results directly demonstrate how oxytocin paired with pup calls rapidly changes brain state, transforming weaker virgin responses into more robust and temporally precise maternal-like responses. The predominant effect of oxytocin is to reduce cortical inhibition within seconds, followed by longer-term modifications over hours proposed to be essential for balancing inhibition with excitation, enhancing spiking and successful maternal care. These synaptic dynamics are analogous to the imbalance of excitation and inhibition for tone-evoked responses in AI during early development when animals have had limited acoustic exposure. After experience, however, tone-evoked excitation and inhibition become balanced over the first few weeks of life. Our findings complement recent studies of neural circuits involved in social behaviour by revealing how ethologically important behaviours with innate components can be quickly shaped and improved by experience. This may exemplify a general mechanism of neuromodulation for social behaviour.
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