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Stress promotes negative affective states, which include anhedonia and passive coping. While these features are in part mediated by neuroadaptations in brain reward circuitry, a comprehensive framework of how stress-induced negative affect may be encoded within key nodes of this circuit is lacking. Here, we show in a mouse model for stress-induced anhedonia and passive coping that these phenomena are associated with increased synaptic strength of ventral hippocampus (VH) excitatory synapses onto D1 medium spiny neurons (D1-MSNs) in the nucleus accumbens medial shell (NAcmSh), and with lateral hypothalamus (LH)-projecting D1-MSN hyperexcitability mediated by decreased inwardly rectifying potassium channel (IRK) function. Stress-induced negative affective states are prevented by depotentiation of VH to NAcmSh synapses, restoring Kir2.1 function in D1R-MSNs, or disrupting co-participation of these synaptic and intrinsic adaptations in D1-MSNs. In conclusion, our data provide strong evidence for a disynaptic pathway controlling maladaptive emotional behavior.

New neurons born in the adult brain undergo a critical period soon after migration to their site of incorporation. During this time, the behavior of the animal may influence the survival or culling of these cells. In the songbird song system, earlier work suggested that adult-born neurons may be retained in the song motor pathway nucleus HVC with respect to motor progression toward a target song during juvenile song learning, seasonal song restructuring, and experimentally manipulated song variability. However, it is not known whether the quality of song per se, without progressive improvement, may also influence new neuron survival. To test this idea, we experimentally altered song acoustic structure by unilateral denervation of the syrinx, causing a poor quality song. We found no effect of aberrant song on numbers of new neurons in HVC, suggesting that song quality does not influence new neuron culling in this region. However, aberrant song resulted in the loss of left-side dominance in new neurons in the auditory region caudomedial nidopallium (NCM), and a bilateral decrease in new neurons in the basal ganglia nucleus Area X. Thus new neuron culling may be influenced by behavioral feedback in accordance with the function of new neurons within that region. We propose that studying the effects of singing behaviors on new neurons across multiple brain regions that differentially subserve singing may give rise to general rules underlying the regulation of new neuron survival across taxa and brain regions more broadly.

Posttraumatic stress disorder (PTSD) is one of the most commonly diagnosed psychiatric disorders in the United States and has been linked to suicidal thoughts and behaviors, yet the role of a PTSD diagnosis on functional impairment among suicidal individuals remains unknown. This study examined the association between PTSD status and functional impairment among military psychiatric inpatients admitted for acute suicide risk (N = 166) with a lifetime history of at least one suicide attempt. Measures of functionality included: (1) alcohol use, (2) sleep quality, (3) social problem-solving, and (4) work and social adjustment. Thirty-eight percent of the sample met criteria for PTSD. Women were more likely than men to meet criteria for PTSD (p = 0.007), and participants who met PTSD criteria had significantly more psychiatric diagnoses (p &lt, 0.001). Service members who met PTSD criteria reported more disturbed sleep (p = 0.003) and greater difficulties with work and social adjustment (p = 0.004) than those who did not meet PTSD criteria. However, functionality measures were not significantly associated with PTSD status after controlling for gender and psychiatric comorbidity. Gender and number of psychiatric comorbidities other than PTSD were significant predictors of PTSD in logistic regression models across four functionality measures. Future studies should assess the additive or mediating effect of psychiatric comorbidities in the association between impaired functioning and PTSD. Clinicians are encouraged to assess and address functionality during treatment with suicidal individuals, paying particular attention to individuals with multiple psychiatric diagnoses.

Psychiatric hospitalization for a suicide attempt (SA), rather than suicide ideation (SI) alone, is a stronger risk indicator for eventual suicide death. Yet, little is known about demographic and clinical characteristics differentiating those admitted for SA versus SI. Understanding these differences has implications for assessment and treatment. A retrospective review of electronic medical records (EMRs) was performed on service members (n = 955) admitted for SA or SI at the Walter Reed Army Medical Center between 2001&ndash, 2006. Service members hospitalized for SA were younger compared to those hospitalized for SI. The proportion of women admitted for SA was significantly higher than those admitted for SI whereas their male counterparts showed the opposite pattern. Patients admitted for SA, versus SI, had significantly higher prevalence of adjustment disorder with mixed disturbance of emotion and conduct (MDEC), personality disorder not otherwise specified (PDNOS), and borderline personality disorder (BPD). Patients admitted for SI had significantly higher prevalence of adjustment disorder with depressed mood and deferred Axis II diagnosis, compared to those admitted for SA. There were no significant between-group differences in the average or median number of documented prior suicide attempts. Findings highlight the need for more standardized assessment, diagnostic decision-making, and documentation practices for all patients.

Fear learning is a fundamental behavioral process that requires dopamine (DA) release. Experience-dependent synaptic plasticity occurs on DA neurons while an organism is engaged in aversive experiences. However, whether synaptic plasticity onto DA neurons is causally involved in aversion learning is unknown. Here, we show that a stress priming procedure enhances fear learning by engaging VTA synaptic plasticity. Moreover, we took advantage of the ability of the ATPase Thorase to regulate the internalization of AMPA receptors (AMPARs) in order to selectively manipulate glutamatergic synaptic plasticity on DA neurons. Genetic ablation of Thorase in DAT+ neurons produced increased AMPAR surface expression and function that lead to impaired induction of both long-term depression (LTD) and long-term potentiation (LTP). Strikingly, animals lacking Thorase in DAT+ neurons expressed greater associative learning in a fear conditioning paradigm. In conclusion, our data provide a novel, causal link between synaptic plasticity onto DA neurons and fear learning.