The cellular basis of depressive disorders is poorly understood1. Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected positive reward or receives a stimulus that predicts aversive conditions (i.e. disappointment or anticipation of a negative outcome)2, 3, 4. LHb neurons project to and modulate dopamine-rich regions such as the ventral-tegmental area (VTA)2, 5 that control reward-seeking behavior6 and participate in depressive disorders7. Here we show in two learned helplessness models of depression that excitatory synapses onto LHb neurons projecting to the VTA are potentiated. Synaptic potentiation correlates with an animal’s helplessness behavior and is due to an enhanced presynaptic release probability. Depleting transmitter release by repeated electrical stimulation of LHb afferents, using a protocol that can be effective on depressed patients8, 9, dramatically suppresses synaptic drive onto VTA-projecting LHb neurons in brain slices and can significantly reduce learned helplessness behavior in rats. Our results indicate that increased presynaptic action onto LHb neurons contributes to the rodent learned helplessness model of depression.

Positron emission tomography (PET) neuroimaging and behavioral assays in rodents are widely used in neuroscience. PET gives insights into the molecular processes of neuronal communication, and behavioral methods analyze the actions that are associated with such processes. These methods have not been directly integrated, because PET studies in animals have until now required general anesthesia to immobilize the subject, which precludes behavioral studies. We present a method for imaging awake, behaving rats with PET that allows the simultaneous study of behavior. Key components include the 'rat conscious animal PET' or RatCAP, a miniature portable PET scanner that is mounted on the rat's head, a mobility system that allows considerable freedom of movement, radiotracer administration techniques and methods for quantifying behavior and correlating the two data sets. The simultaneity of the PET and behavioral data provides a multidimensional tool for studying the functions of different brain regions and their molecular constituents.

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Disgust may be a key emotion and target for psychotherapeutic interventions in borderline personality disorder (BPD) and posttraumatic stress disorder (PTSD) at explicit and implicit-automatic levels. However, automatically activated disgust reactions in individuals with these disorders have not been studied. Disgust and its correlation with childhood abuse were assessed in women with BPD, but without PTSD; women with PTSD, but without BPD; women with BPD and PTSD; and healthy women. Disgust sensitivity, anxiety and depression were measured by self-report. Implicit disgust-prone (relative to anxiety-prone) self-concept was assessed using the Implicit Association Test. Women with BPD and/or PTSD reported more disgust sensitivity than controls. The implicit self-concept among patients was more disgust-prone (relative to anxiety-prone) than in controls. Women with BPD, with PTSD, or BPD and PTSD did not differ significantly in self-reported disgust levels or implicit disgust-related self-concept. Among women with BPD and/or PTSD, current psychiatric comorbidity (major depression, anxiety disorder, eating disorder, or substance-related disorder) did not affect disgust-related variables. More severe physical abuse in childhood was associated with a more anxiety-prone (less disgust-prone) implicit self-concept. Independent of psychiatric comorbidity, disgust appears to be elevated at implicit and explicit levels in trauma-related disorders. Psychotherapeutic approaches to address disgust should take implicit processes into account.

In 28- to 30-month-old rats, in vitro short-term and long-term potentiation (STP and LTP) were measured in area CA1 of the hippocampus in seven superior and seven inferior learners, that were selected from a pool of 40 rats based on water maze escape performance over a period of 9 days. The aim was to examine whether levels of STP and LTP could account for group differences in learning of water maze escape, spatial preference and wall (thigmotaxis)-avoidance and in short-term retention of an inhibitory avoidance task. There was no significant group difference in open-field exploration, i.e. the number of rearings. In contrast to expectation, the superior and inferior learners did not differ significantly from each other in levels of STP and LTP. However, variability in escape and spatial learning, but not thigmotaxis-avoidance learning, was significantly predicted by variability in STP and LTP in the superior group. Also, open-field exploratory rearings were significantly correlated with STP and LTP as well as with maze escape learning in the superior group. The results show that, in the aged superior group, levels of CA1 STP and LTP coincided with residual water maze escape and spatial preference learning as well as open-field exploration, i.e. behavioural expressions known to be related to hippocampal functioning, but not with learning to avoid thigmotaxis in the maze. The lack of such correlations in the inferior group may be due to the severe impairment in escape and spatial preference learning and/or the influence of yet unknown third variables on these relationships.