The Human Brain Project: Creating a European Research Infrastructure to Decode the Human Brain.

Decoding the human brain is perhaps the most fascinating scientific challenge in the 21st century. The Human Brain Project (HBP), a 10-year European Flagship, targets the reconstruction of the brain's multi-scale organization. It uses productive loops of experiments, medical, data, data analytics, and simulation on all levels that will eventually bridge the scales. The HBP IT architecture is unique, utilizing cloud-based collaboration and development platforms with databases, workflow systems, petabyte storage, and supercomputers. The HBP is developing toward a European research infrastructure advancing brain research, medicine, and brain-inspired information technology.

Isolation-induced vocalization in the infant rat depends on the nucleus accumbens.

Mammalian infants vocalize when socially isolated. Vocalization guides the return of the caregiver and thereby maintains an environment critical to the infant's survival. Although the role of the periaqueductal gray area (PAG) in these vocalizations is established, other aspects of the relevant neural circuitry remain under-studied. Here we report that output from the nucleus accumbens (Acb) is necessary for isolation-induced vocalizations of infant rats aged postnatal days (PND) 11-13. Local inhibition via infusion of the GABAA agonist muscimol (.8 µg/side) of the Acb, but not the dorsolateral striatum, blocked isolation-induced vocalizations, independent of whether the isolation was at room temperature, followed a brief reunion with the dam, or occurred in a cool (10 °C) environment. These findings highlight a possible anatomical area mediating the mammalian infant response to social separation and, more generally, to the development of social attachment.

Dopamine's role in social modulation of infant isolation-induced vocalization: I. Reunion responses to the dam, but not littermates, are dopamine dependent.

Rat pups' vocalization during social separation and the cessation of vocalization upon social reunion (contact quieting) model early life affiliative relationships. The present study examined the roles of dopamine (DA) receptors in regulating contact quieting. Contact quieting to the dam, but not to littermates, was disrupted by either blockade or exogenous stimulation of DA D1-like receptors. The D2 antagonist raclopride also prevented the quieting effect of reunion with the dam and had a lesser effect on the quieting properties of littermates. In contrast, the D2 agonist quinpirole permitted or enhanced contact quieting. Combined systemic and local striatal administration of D2 ligands showed that stimulation of striatal D2 receptors can enhance, but is not necessary for, contact quieting to the dam. These results are consistent with the literature linking the neural mechanisms of affiliation and reinforcement. This is also the first demonstration that the neurochemical substrates of an infant comfort response to dams differ from a behaviorally similar response to siblings.

Dopamine's role in social modulation of infant isolation-induced vocalization: II. Maternally modulated infant separation responses are regulated by D1- and D2-family dopamine receptors.

Mammalian infant behavior directed toward caregivers is critical to survival and may play a role in establishing social bonds. Most mammalian infants vocalize when isolated. Rat pups vocalize at a higher rate when isolated following an interaction with an adult female than after an interaction with littermates, a phenomenon termed maternal potentiation. We previously reported that the D2 receptor family agonist quinpirole disrupts maternal potentiation at a dose that does not alter vocalization rate following contact with littermates. Here we further examine the role of dopamine in maternal potentiation by testing effects of both D1 and D2 receptor family ligands, alone and in combination, on maternal potentiation. We tested the drugs' effects on isolation vocalization subsequent to littermate contact and then another isolation preceded by a brief "reunion" period of exposure either to the anesthetized dam or a handling-only "pickup" condition. D2 receptor stimulation blocked the increase in vocalizations following reunion with the dam. The D2 agonist effect in the dam-reunion condition was much larger than its small effect in the pickup condition, providing further evidence that D2 receptors exert a selective modulation of maternal potentiation. On the other hand, systemic administration of the D1 agonist SKF81297 reduced isolation vocalizations nonspecifically, across all the experimental conditions. Finally, the D1 and D2 receptor dual antagonist, alpha-flupenthixol, increased isolation vocalizations and disrupted potentiation, but at doses that also inhibited locomotion. We conclude that D2 receptor family activation has a more selective effect of disrupting maternal potentiation than D1 receptor family activation.

Ventral striatum dopamine D2 receptor activity inhibits rat pups' vocalization response to loss of maternal contact.

Most mammalian infants vocalize when isolated. The vocalization promotes caregiver proximity, which is critical to survival. If, before isolation, a rat pup has contact with its dam, its isolation vocalization rate is increased (maternal potentiation) relative to isolation preceded only by littermate contact. Prior work showed that systemic administration of a D2 receptor agonist blocks maternal potentiation at doses that do not alter baseline vocalization. In this study, infusion of quinpirole (2 microg/side) into the nucleus accumbens also blocks maternal potentiation. Infusion of the accumbens with the D2 antagonist raclopride (4 microg/side) prevents systemic quinpirole from blocking potentiation. Quinpirole infusion in the dorsal striatum did not affect maternal potentiation and infusion of raclopride in the dorsal striatum did not reverse the block of maternal potentiation by systemic quinpirole. Vocalization results after a second vehicle infusion on a given day are no different than the results following an initial vehicle infusion, so experimental design can not account for the effects of drug infusions. Because activity level was increased by both dorsal and ventral striatum infusions, activity level can not account for the results.

Maternally modulated infant separation responses are regulated by D2-family dopamine receptors.

Although dopamine is necessary for mammalian adult pair-bond formation and maternal behavior, its function in infant social behavior and attachment has been less thoroughly explored. The vocalization rate of an isolated rat pup is influenced by recent social contact. Interactions with the dam potentiate vocalization rate. Interactions with littermates or adult males do not. Systemic administration of the D2-family agonist quinpirole specifically blocked maternal potentiation at doses that did not alter vocalization rate in an isolation prior to dam contact. This result was not explained by quinpirole's effects on body temperature or locomotion. The results are consistent with a role for dopamine in infant social behavior.