Aversive memories are important for survival, and dopaminergic signaling in the hippocampus has been implicated in aversive learning. However, the source and mode of action of hippocampal dopamine remain controversial. Here, we utilize anterograde and retrograde viral tracing methods to label midbrain dopaminergic projections to the dorsal hippocampus. We identify a population of midbrain dopaminergic neurons near the border of the substantia nigra pars compacta and the lateral ventral tegmental area that sends direct projections to the dorsal hippocampus. Using optogenetic manipulations and mutant mice to control dopamine transmission in the hippocampus, we show that midbrain dopamine potently modulates aversive memory formation during encoding of contextual fear. Moreover, we demonstrate that dopaminergic transmission in the dorsal CA1 is required for the acquisition of contextual fear memories, and that this acquisition is sustained in the absence of catecholamine release from noradrenergic terminals. Our findings identify a cluster of midbrain dopamine neurons that innervate the hippocampus and show that the midbrain dopamine neuromodulation in the dorsal hippocampus is sufficient to maintain aversive memory formation.

Objective To describe and provide the rationale for a randomized controlled trial for depression or anxiety after moderate to severe traumatic brain injury (TBI), which will test 2 treatments based on behavioral activation (BA), a promising model to promote both positive mood and increased activity in this population. Design Randomized controlled trial with masked outcome assessment. Setting Outpatient catchment area of 1 TBI treatment center. Participants Community-dwelling persons (N=60) with moderate-severe TBI at least 6 months prior to enrollment and greater than mild depression or anxiety. Interventions Participants will be randomized 2:1 into an 8-session treatment, behavioral activation with technology, consisting of 6 face-to-face sessions and 2 via phone, with mood and activity monitoring conducted via ecological momentary assessment on a smartphone; or a single session incorporating BA principles followed by 8 weeks of activity reminders in the form of implementation intentions, delivered as text messages. Main Outcome Measures Brief Symptom Inventory-18 (primary outcome); Environmental Reward Observation Scale, Behavioral Activation for Depression Scale, Participation Assessment with Recombined Tools-Objective, Diener Satisfaction With Life Scale, Quality of Life after Brain Injury scale, Patient Global Impression of Change. Outcomes are measured midway through intervention, after treatment cessation (primary outcome), and at 2-month follow-up. A treatment enactment interview is administered after the follow-up to ascertain to what extent participants continue to engage in activities and use strategies promoted during trial participation. Results N/A. Conclusions N/A.

Purpose: To describe where, with whom, and how time was spent daily, and to characterize positive and negative affect, boredom, enjoyment, and perceived accomplishment as a function of time, activity, location, and social context, in people with chronic moderate-severe traumatic brain injury and depression/anxiety. Research Method: Participants (N = 23) responded to a smartphone app five times daily for approximately 2 weeks prior to treatment in a trial of Behavioral Activation. The app queried activity and physical/social context; concurrent positive and negative affect; and perceived boredom, enjoyment, and accomplishment. Descriptive statistics captured time use, and linear mixed models were used to analyze relations between affect and contextual factors. Results: Ecological Momentary Assessment (EMA) response rate was positively correlated with integrity of episodic memory and education. Participants spent most time at home versus elsewhere, and alone versus with others. The most frequent activity was watching TV. Mixed model results based on 17 participants with .33% response rate showed that positive affect was associated with being outside of home, and with other people; however, socializing was related to higher negative affect. TV watching was related to lower negative affect but also low accomplishment. Conclusions: EMA can provide unique information on the effects of social context and activity on mood in TBI. Clinicians should consider negative as well as positive affect associated with increasing social participation. Impact and ImplicationsEcological Momentary Assessment (EMA) is generally feasible for individuals with moderate-severe traumatic brain injury (TBI), but cognitive supports such as extra training and supervised practice might be needed to boost response rate for individuals with lower education or more severe memory impairment. Individuals with moderate-severe TBI may spend a large proportion of time alone and at home, and relatively little time engaged in outdoor activities and exercise. Positive affect is associated with productive activity such as working and doing chores. These findings point to the need for interventions that promote activity and community engagement after TBI. Spending time with others may be associated with both positive and negative emotional states, suggesting that clinicians might encourage a graded approach (beginning with lower-stress activities) to increasing socialization for people with moderate-severe TBI.

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