ReviewTranslating the Habenula—From Rodents to Humans
Section snippets
Rodents
Most knowledge on Hb connectivity, as well as structural characteristics and neurochemistry of Hb neurons, stems from studies in animals. In brief, retrograde and anterograde tracing studies in rodents (4, 16) and electrophysiological studies in nonhuman primates (5) have provided a detailed description of afferent and efferent connections of the Hb complex, summarized in Figure 1. Because of their distinct input/output structures, the LHb and MHb seem to form parallel channels, regulating the
Rodents
In animal research, the notion that LHb hyperactivity is associated with depressive-like symptoms, whereas LHb inhibition improves depressive-like behaviors, is well established [reviewed in (12)]. In the late 1980s, a first rat study showed elevated deoxyglucose metabolism in LHb across three behavioral models of depression (27, 28). Among main further findings, an LHb lesion study showed reduced depressive-like behaviors and increased 5-HT turnover in the dorsal raphe nucleus of rats
Rodents
In addiction research, animal studies have been extraordinarily productive to demonstrate the importance of Hb in neuroadaptations to drugs of abuse and negative consequences of drug dependence. Here, we summarize current knowledge with emphasis on recent studies.
Several rodent studies have proposed a role for LHb in cocaine reward and dependence. In a mouse model of cocaine conditioned place preference, c-fos immunohistochemistry showed increased neuronal activation in the LHb of mice
Schizophrenia
Because of the complex connectivity of the Hb to multiple forebrain and hindbrain circuits, similar in rodents, nonhuman primates, and humans, it is anticipated that Hb activity affects multiple dimensions of normal behavior, with implications for disease beyond depression and addiction. Here, we focus on the possible role of the Hb in schizophrenia.
Tightly linked to predicting errors are decision-making processes, and rat studies have demonstrated causal implication of the LHb in subjective
Challenges and Future Directions
In this review, we have organized rodent and human data in three major psychiatric disease areas: depression, drug dependence, and other potential disease areas of psychiatry, notably schizophrenia. We have also added a section on pain in the Supplement. Table 1 summarizes functional consequences of Hb manipulations in both rodents and humans within the four categories.
Basic research in laboratory animals has revealed the Hb as a core integration center, which influences many aspects of
Acknowledgments and Disclosures
This work was supported by the Canada Research Chairs, the Monique H. Bourgeois Chair in Pervasive Developmental Disorders (McGill University), and the National Institutes of Health Grant Nos. NIH-NIAAA 16658 and NIH-NIDA 005010.
We thank Maria Osikowicz for comments and careful reading of the manuscript.
The authors report no biomedical financial interests or potential conflicts of interest.
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