Oxytocin mediates early experience–dependent cross-modal plasticity in the sensory cortices

Abstract

Sensory experience is critical to development and plasticity of neural circuits. Here we report a new form of plasticity in neonatal mice, where early sensory experience cross-modally regulates development of all sensory cortices via oxytocin signaling. Unimodal sensory deprivation from birth through whisker deprivation or dark rearing reduced excitatory synaptic transmission in the correspondent sensory cortex and cross-modally in other sensory cortices. Sensory experience regulated synthesis and secretion of the neuropeptide oxytocin as well as its level in the cortex. Both in vivo oxytocin injection and increased sensory experience elevated excitatory synaptic transmission in multiple sensory cortices and significantly rescued the effects of sensory deprivation. Together, these results identify a new function for oxytocin in promoting cross-modal, experience-dependent cortical development. This link between sensory experience and oxytocin is particularly relevant to autism, where hypersensitivity or hyposensitivity to sensory inputs is prevalent and oxytocin is a hotly debated potential therapy.

Developmental Perspectives on Oxytocin and Vasopressin

“…This difference is consistent with in vivo results that vasopressin emerges earlier than oxytocin and is also consistent with the hypothesis that developmental oxytocin is activity dependent (Zheng et al, 2014). However, oxytocin mRNA levels in primary cultures derived from postnatal rat brains did not appear to be affected by lack of serum in the culture media or the presence of tetrodotoxin (Wray et al, 1991).…”

“…This consistent and direct neurodevelopmental translation of peak expression for both AVPR1A and OXTR suggests that mice will be very valuable models of the activity-dependent effects of oxytocin and vasopressin on neocortical development. The functional significance of the robust transient peak of OXTR in the neocortex of mice has recently been demonstrated by Zheng et al (2014), and will be discussed in much further detail below.…”

“…Methylation of DNA contributes to tissue-specific and dynamic or stimulus-evoked regulation of gene expression. Methylation of the mouse Oxtr gene is associated with brain region-specific (Zheng et al, 2014), copyright Nature Publishing Group. *Po0.05, **Po0.01, ***Po0.001.…”

“…Hypothesis in which development shines light on the 'Dark Matter of Social Neuroscience', or the unclarified neural mechanisms between social sensory inputs and social behavior outputs (Insel, 2010). (a) During developmental sensitive periods, parental nurturing (Kojima et al, 2012;Weisman et al, 2012) and/or sensory inputs (Zheng et al, 2014) drive the activity of the PVN resulting in increased release of oxytocin. This oxytocin can regulate multi-sensory plasticity in the neocortex.…”

Actin Aggregations Mark the Sites of Neurite Initiation

“…For live imaging experiments, the electroporated cortical hemisphere from P0 pups was cultured. To visualize GFP-actinin localization in brain slices, immunohistochemistry was carried out as previously described [54]. GFP antibody was used to enhance the GFP-actinin signal.…”