Neural circuitry for maternal oxytocin release induced by infant cries.

Oxytocin is a neuropeptide that is important for maternal physiology and childcare, including parturition and milk ejection during nursing1-6. Suckling triggers the release of oxytocin, but other sensory cues-specifically, infant cries-can increase the levels of oxytocin in new human mothers7, which indicates that cries can activate hypothalamic oxytocin neurons. Here we describe a neural circuit that routes auditory information about infant vocalizations to mouse oxytocin neurons. We performed in vivo electrophysiological recordings and photometry from identified oxytocin neurons in awake maternal mice that were presented with pup calls. We found that oxytocin neurons responded to pup vocalizations, but not to pure tones, through input from the posterior intralaminar thalamus, and that repetitive thalamic stimulation induced lasting disinhibition of oxytocin neurons. This circuit gates central oxytocin release and maternal behaviour in response to calls, providing a mechanism for the integration of sensory cues from the offspring in maternal endocrine networks to ensure modulation of brain state for efficient parenting.

Oxytocin promotes prefrontal population activity via the PVN-PFC pathway to regulate pain.

Neurons in the prefrontal cortex (PFC) can provide top-down regulation of sensory-affective experiences such as pain. Bottom-up modulation of sensory coding in the PFC, however, remains poorly understood. Here, we examined how oxytocin (OT) signaling from the hypothalamus regulates nociceptive coding in the PFC. In vivo time-lapse endoscopic calcium imaging in freely behaving rats showed that OT selectively enhanced population activity in the prelimbic PFC in response to nociceptive inputs. This population response resulted from the reduction of evoked GABAergic inhibition and manifested as elevated functional connectivity involving pain-responsive neurons. Direct inputs from OT-releasing neurons in the paraventricular nucleus (PVN) of the hypothalamus are crucial to maintaining this prefrontal nociceptive response. Activation of the prelimbic PFC by OT or direct optogenetic stimulation of oxytocinergic PVN projections reduced acute and chronic pain. These results suggest that oxytocinergic signaling in the PVN-PFC circuit constitutes a key mechanism to regulate cortical sensory processing.

Music Upper Limb Therapy-Integrated Provides a Feasible Enriched Environment and Reduces Post-stroke Depression: A Pilot Randomized Controlled Trial.

OBJECTIVE: This study's aims were to refine Music Upper Limb Therapy-Integrated (MULT-I) to create a feasible enriched environment for stroke rehabilitation and compare its biologic and behavioral effects with that of a home exercise program (HEP). DESIGN: This was a randomized mixed-methods study of 30 adults with post-stroke hemiparesis. Serum brain-derived neurotrophic factor and oxytocin levels measured biologic effects, and upper limb function, disability, quality of life, and emotional well-being were assessed as behavioral outcomes. Participant experiences were explored using semistructured interviews. RESULTS: MULT-I participants showed reduced depression from preintervention to postintervention as compared with HEP participants. Brain-derived neurotrophic factor levels significantly increased for MULT-I participants but decreased for HEP participants, with a significant difference between groups after excluding those with post-stroke depression. MULT-I participants additionally improved quality of life and self-perceived physical strength, mobility, activity, participation, and recovery from preintervention to postintervention. HEP participants improved upper limb function. Qualitatively, MULT-I provided psychosocial support and enjoyment, whereas HEP supported self-management of rehabilitation. CONCLUSIONS: Implementation of a music-enriched environment is feasible, reduces post-stroke depression, and may enhance the neural environment for recovery via increases in brain-derived neurotrophic factor levels. Self-management of rehabilitation through an HEP may further improve upper limb function.

Capacities and neural mechanisms for auditory statistical learning across species.

Statistical learning has been proposed as a possible mechanism by which individuals can become sensitive to the structures of language fundamental for speech perception. Since its description in human infants, statistical learning has been described in human adults and several non-human species as a general process by which animals learn about stimulus-relevant statistics. The neurobiology of statistical learning is beginning to be understood, but many questions remain about the underlying mechanisms. Why is the developing brain particularly sensitive to stimulus and environmental statistics, and what neural processes are engaged in the adult brain to enable learning from statistical regularities in the absence of external reward or instruction? This review will survey the statistical learning abilities of humans and non-human animals with a particular focus on communicative vocalizations. We discuss the neurobiological basis of statistical learning, and specifically what can be learned by exploring this process in both humans and laboratory animals. Finally, we describe advantages of studying vocal communication in rodents as a means to further our understanding of the cortical plasticity mechanisms engaged during statistical learning. We examine the use of rodents in the context of pup retrieval, which is an auditory-based and experience-dependent form of maternal behavior.

Long-term recording reliability of liquid crystal polymer µECoG arrays.

OBJECTIVE: The clinical use of microsignals recorded over broad cortical regions is largely limited by the chronic reliability of the implanted interfaces. APPROACH: We evaluated the chronic reliability of novel 61-channel micro-electrocorticographic (µECoG) arrays in rats chronically implanted for over one year and using accelerated aging. Devices were encapsulated with polyimide (PI) or liquid crystal polymer (LCP), and fabricated using commercial manufacturing processes. In vitro failure modes and predicted lifetimes were determined from accelerated soak testing. Successful designs were implanted epidurally over the rodent auditory cortex. Trends in baseline signal level, evoked responses and decoding performance were reported for over one year of implantation. MAIN RESULTS: Devices fabricated with LCP consistently had longer in vitro lifetimes than PI encapsulation. Our accelerated aging results predicted device integrity beyond 3.4 years. Five implanted arrays showed stable performance over the entire implantation period (247-435 d). Our regression analysis showed that impedance predicted signal quality and information content only in the first 31 d of recordings and had little predictive value in the chronic phase (>31 d). In the chronic phase, site impedances slightly decreased yet decoding performance became statistically uncorrelated with impedance. We also employed an improved statistical model of spatial variation to measure sensitivity to locally varying fields, which is typically concealed in standard signal power calculations. SIGNIFICANCE: These findings show that µECoG arrays can reliably perform in chronic applications in vivo for over one year, which facilitates the development of a high-density, clinically viable interface.

Dynamics of auditory cortical activity during behavioural engagement and auditory perception.

Behavioural engagement can enhance sensory perception. However, the neuronal mechanisms by which behavioural states affect stimulus perception remain poorly understood. Here we record from single units in auditory cortex of rats performing a self-initiated go/no-go auditory task. Self-initiation transforms cortical tuning curves and bidirectionally modulates stimulus-evoked activity patterns and improves auditory detection and recognition. Trial self-initiation decreases the rate of spontaneous activity in the majority of recorded cells. Optogenetic disruption of cortical activity before and during tone presentation shows that these changes in evoked and spontaneous activity are important for sound perception. Thus, behavioural engagement can prepare cortical circuits for sensory processing by dynamically changing sound representation and by controlling the pattern of spontaneous activity.

Long-term modification of cortical synapses improves sensory perception.

Synapses and receptive fields of the cerebral cortex are plastic. However, changes to specific inputs must be coordinated within neural networks to ensure that excitability and feature selectivity are appropriately configured for perception of the sensory environment. We induced long-lasting enhancements and decrements to excitatory synaptic strength in rat primary auditory cortex by pairing acoustic stimuli with activation of the nucleus basalis neuromodulatory system. Here we report that these synaptic modifications were approximately balanced across individual receptive fields, conserving mean excitation while reducing overall response variability. Decreased response variability should increase detection and recognition of near-threshold or previously imperceptible stimuli. We confirmed both of these hypotheses in behaving animals. Thus, modification of cortical inputs leads to wide-scale synaptic changes, which are related to improved sensory perception and enhanced behavioral performance.