Coma and vegetative states: state of the art and proposal of a novel approach combining existing coma scales.

Brain damage of various aetiologies can lead to different disorders of consciousness (DOC), varying from coma to vegetative, to minimally conscious states. Each state is characterised by a different degree of wakefulness, awareness, pain sensitivity and is differentially handled with respect to treatment, ethical considerations and end-oflife decisions. Thus, its correct identification is crucial while devising or modulating appropriate treatment strategies. Actually, the main coma scales cannot always accurately determine the state of consciousness of an individual, while other tools (e.g. imaging techniques) present a certain degree of uncertainty. A complementary approach may be constituted by a 24-hour observation of patients, for a sufficient period of days, using an ad hoc behavioural scale, further correlated with physiological and pharmacological parameters measured on patients. The method herein described might help recognising the presence of consciousness of the different DOC patients, and thus discerning a vegetative from a minimally conscious state.

The richness of social stimuli shapes developmental trajectories: Are laboratory mouse pups impoverished?

The early environment is crucial for brain and behavior development. In particular, social experiences involving the mother and the peers are critical in shaping the adult individual. Though animal models of psychiatric disorders have widely investigated the relevance of the mother-offspring interaction, the peer interaction has so far been rarely studied. The communal nest (CN) is an innovative experimental strategy that favors a more comprehensive investigation of the long-term effects of both components. CN is a rearing condition employed by up to 90% of mouse females in naturalistic settings and consists of a single nest where two or more mothers keep their pups together and share care-giving. In a CN, the developing pup is exposed to high levels of both maternal care and interaction with peers. At adulthood, these mice display relevant changes in bran function and behavior, including high levels of neural plasticity markers, such as BDNF, and elaborate adult social competences. Overall, on the one hand, CN is an experimental approach complementary to the ones currently used that allows to investigate how the early environment determines developmental trajectories. On the other, it may represent a strategy to improve the study of animal models of psychiatric disorders characterized by social dysfunction, such as major depression, autism and attention deficit hyperactivity disorder. Indeed, the more elaborate social competences shown by these mice at adulthood may allow to better characterize deficits in the social domain induced by genetic and/or environmental manipulations.

Early life influences on emotional reactivity: evidence that social enrichment has greater effects than handling on anxiety-like behaviors, neuroendocrine responses to stress and central BDNF levels.

During the early post-natal phases the brain is experience-seeking and provided by a considerable plasticity which allows a fine tuning between the external environment and the developing organism. Since the early work of Seymour Levine, an impressive amount of research has clearly shown that stressful experiences exert powerful effects on the brain and body development. These effects can last throughout the entire life span influencing brain function and increasing the risk for depression and anxiety disorders. The mechanisms underlying the effects of early stress on the developing organism have been widely studied in rodents through experimental manipulations of the post-natal environment, such as handling, which have been shown to exert important effects on the emotional phenotype and the response to stress. In the present paper we review the relevant literature and present some original data indicating that, compared to handling, which imposes an external manipulation on the mother-infant relationship, social enrichment, in the form of communal rearing, in mice has very profound effects on animal's emotionality and the response to stress. These effects are also accompanied by important changes in central levels of brain-derived neurotrophic factor. The present data indicate that communal rearing has more pervasive effects than handling, strengthening previous data suggesting that it is a good animal model of reduced susceptibility to depression-like behavior. Overall, the availability of ever more sophisticated animal models represents a fundamental tool to translate basic research data into appropriate interventions for humans raised under traumatic or impoverished situations.

Moderate neonatal stress decreases within-group variation in behavioral, immune and HPA responses in adult mice.

BACKGROUND: The significance of behavioral neuroscience and the validity of its animal models of human pathology largely depend on the possibility to replicate a given finding across different laboratories. Under the present test and housing conditions, this axiom fails to resist the challenge of experimental validation. When several mouse strains are tested on highly standardized behavioral test batteries in different laboratories, significant strain x lab interactions are often detected. This limitation, predominantly due to elevated within-group variability observed in control subjects, increases the number of animals needed to address fine experimental questions. Laboratory rodents display abnormal stress and fear reactions to experimental testing, which might depend on the discrepancy between the stability of the neonatal environment and the challenging nature of the adult test and housing conditions. METHODOLOGY/PRINCIPAL FINDINGS: Stimulating neonatal environments (e.g. brief maternal separations, increased foraging demands or maternal corticosterone supplementation) reduce stress and fear responses in adulthood. Here we tested whether reduced fearfulness associated with experimental testing would also reduce inter-individual variation. In line with our predictions, we show that a moderate elevation in neonatal corticosterone through maternal milk significantly reduces fear responses and inter-individual variability (average 44%) in adult mouse offspring. CONCLUSIONS/SIGNIFICANCE: We observed reduced variation in pain perception, novelty preference, hormonal stress response and resistance to pathogen infection. This suggests that the results of this study may apply to a relatively broad spectrum of neuro-behavioral domains. Present findings encourage a reconsideration of the basic principles of neonatal housing systems to improve the validity of experimental models and reduce the number of animals used.

Methods in the analysis of maternal behavior in the rodent.

The aim of this unit is to provide a set of fundamental protocols to assess maternal behavior in rats and mice. Parental behavior in rodents is characterized by a rather complex set of behavioral items, which are described in great detail. A special emphasis has been placed on listing the many intervening variables that can bias the correct assessment of maternal behavior and the modifications to that behavior resulting from exposure to drugs or toxic compounds. Because changes in maternal behavior can be very subtle, the accuracy of the protocols can enhance the likelihood of detecting minor differences in behavior resulting from the experimental procedures. In addition, some suggestions are given on the most appropriate methods of data collection and their statistical analysis.