Efficacy of Web-Based Interventions on Depression and Anxiety in Cancer Caregivers: A Systematic Review and Meta-Analysis.

OBJECTIVE: This study aimed to evaluate the effectiveness of web-based interventions in depression and anxiety among informal caregivers of patients with cancer. METHODS: Databases such as PubMed, Cochrane, Web of Science, Embase, CINAHL, and PsycINFO were systematically searched from inception to April 15, 2024. Eligible studies encompassed randomized controlled trials (RCTs) focusing on web-based interventions tailored to informal caregivers of patients with cancer. The effect size was calculated as the standardized mean difference (SMD) with a 95% confidence interval (CI) utilizing a random effects model. The risk of bias was assessed independently utilizing Cochrane's Risk of Bias Tool (version 2.0) for RCTs. RESULTS: A total of 12 RCTs were incorporated into this meta-analysis. Web-based interventions demonstrated a significant effect in ameliorating depression among informal caregivers of patients with cancer compared to the control group (SMD = -0.21, 95% CI = -0.36 to -0.05, p < 0.01, I2 = 15%). Additionally, a significant effect was also observed in alleviating anxiety (SMD = -0.20, 95% CI = -0.36 to -0.05, p = 0.77, I2 = 0%). CONCLUSIONS: Web-based interventions might be effective in reducing depression and anxiety among informal caregivers of patients with cancer. Nevertheless, several studies with an overall high risk of bias were included. As a result of the limited number and heterogeneity of the studies included in the subgroup analysis, deriving definitive conclusions on the most effective intervention components was challenging. Therefore, further studies incorporating high-quality research are warranted.

Inequities Among Cancer Caregivers with Diverse Identities: A Review of the Literature and Future Directions.

PURPOSE OF REVIEW: The number of older adults with cancer relying on support from caregivers continues to increase. Health disparities in older adults with cancer often extend to their caregivers. This review aims to assess the state of cancer caregiving research in historically underrepresented diverse populations and provide recommendations for future research and policy. RECENT FINDINGS: Research on caregivers of older adults with cancer from diverse backgrounds has primarily been descriptive. Health disparities for historically underrepresented caregivers (LGBTQ + , BIPOC, rural, young adults, youth) exist across several dimensions (e.g., financial, mental, and physical health, and access to caregiver support). Few published studies have closely examined the unique experiences of these caregivers nor provided culturally appropriate tailored interventions. Health equity research within caregiving populations is in its infancy. Priorities for future work should focus on identifying modifiable targets for intervention, changing systems-level processes in acknowledging and supporting caregivers, and creating policies that reduce financial inequities of caregiving.

Perspectives of caregivers of older adults with acute myeloid leukemia during initial hypomethylating agents and venetoclax chemotherapy.

BACKGROUND: Older adults with AML commonly receive a hypomethylating agent (HMA) as first-line therapy. The addition of venetoclax (VEN) to HMAs has been shown to improve remission rates and overall survival. The use of combination therapy (HMA + VEN) requires frequent follow-up, results in longer infusion times, and likely increases caregiver responsibility at home. We describe experiences of informal caregivers (family/friends) providing care to older adults with AML receiving HMA + VEN. METHODS: Fourteen caregivers of older adults with AML receiving HMA + VEN (September 2020 to September 2021) were recruited as part of a control group of an ongoing NIH-funded clinical trial. Semi-structured interviews were conducted to gain initial insight into caregiver experiences at the start of HMA + VEN treatment. Two researchers analyzed the data using thematic content analysis. Data saturation occurred when no new themes were found in subsequent interviews, but all interviews were coded and synthesized. RESULTS: Of the 14 caregivers interviewed, the majority were spouses (n = 10), female (n = 13), and aged 45 to 83 (median age 65). We identified five themes: (1) the impact of an AML diagnosis in older adulthood, (2) care recipient condition changes, (3) perspectives of caregiving roles and tasks, (4) factors influencing caregiving experiences, and (5) support system roles. CONCLUSIONS AND IMPLICATIONS: Caregivers for older adults with AML report a range of experiences navigating health systems, caregiving responsibilities, and resource needs. The risk for caregiver burden and unmet needs should be addressed to improve caregivers' abilities to provide care.

Ethical Considerations of Social Media to Recruit Caregivers of Children With Cancer.

BACKGROUND: Social media platforms are useful for recruiting hard-to-reach populations, such as caregivers of children with cancer, for research. However, there are unique ethical considerations in using social media. OBJECTIVES: The aim of the study was to describe the methods used to recruit hard-to-reach caregivers (parents of children with cancer) for research and related ethical considerations. METHODS: We used The Belmont Report tenets (respect for persons, beneficence, and justice) as a guiding framework to identify issues relevant to social media recruitment of hard-to-reach populations and to describe how we addressed these issues in our study. RESULTS: We engaged leaders of two online communities that offer peer support for caregivers of children with cancer to help with recruitment to our study on financial effect of pediatric cancer. We identified issues in using social media for recruiting hard-to-reach populations in alignment with The Belmont Report, including risk for subject selection bias, privacy rights, protecting identity of participants, data security issues, and access to research. We addressed issues by deliberate study design decisions and engagement with online community advocates. DISCUSSION: Using social media to recruit hard-to-reach populations may be a successful way to engage them in research. Although researchers may remain compliant with the institutional review board of their facilities and are faithful to the tenets of The Belmont Report, unanticipated ethical issues may arise directly or indirectly as a result of using social media. This article identifies these issues and provides suggestions for dealing with them.

Positive psychological states and stress responses in caregivers of adults receiving an allogeneic bone marrow transplant: A study protocol.

AIMS: This protocol directs a study that aims to: (a) describe the caregiver's experience over 8-12 weeks after an index adult patient's allogeneic bone marrow transplant (BMT) for advanced cancer using a case-oriented approach and mixed methods, with qualitative methods in the foreground; and (b) explore networks of relationships among psycho-neurological symptoms, positive psychological states and caregiver health. DESIGN: Case-oriented longitudinal design using multiple data types and analytic approaches. METHODS: Data will be collected from 10-12 caregivers. The sample will be recruited from a large public hospital in the southeastern United States using maximum variation sampling (e.g., caregiver race/ethnicity, relationship to patient, age, education, and number of caregiving roles). Participants will be asked to complete weekly surveys, have their blood drawn bi-weekly and participate in an interview each month during the study period (~100 days). Aim 1 analysis will include directed content analysis and case-oriented visual analysis. Aim 2 analysis will include symptom network estimation of psycho-neurological symptoms, positive psychological states, and caregiver health. Institutional review board approval was obtained August 2018. DISCUSSION: Results will provide an in-depth description of caregivers' experiences in the 100 days after BMT. Findings will inform generation of hypotheses and identification of targets for interventions to improve caregiver's experiences after BMT. IMPACT: This in-depth multi-method longitudinal study to describe caregivers of adult patients receiving an allogeneic BMT is an essential step in understanding caregivers' complex responses to chronic stress and the role of positive psychological states. The results from this study will inform future research on chronic stress processes, intense caregiving, and intervention development.

Ventral tegmental area GABA projections pause accumbal cholinergic interneurons to enhance associative learning.

The ventral tegmental area (VTA) and nucleus accumbens (NAc) are essential for learning about environmental stimuli associated with motivationally relevant outcomes. The task of signalling such events, both rewarding and aversive, from the VTA to the NAc has largely been ascribed to dopamine neurons. The VTA also contains GABA (γ-aminobutyric acid)-releasing neurons, which provide local inhibition and also project to the NAc. However, the cellular targets and functional importance of this long-range inhibitory projection have not been ascertained. Here we show that GABA-releasing neurons of the VTA that project to the NAc (VTA GABA projection neurons) inhibit accumbal cholinergic interneurons (CINs) to enhance stimulus-outcome learning. Combining optogenetics with structural imaging and electrophysiology, we found that VTA GABA projection neurons selectively target NAc CINs, forming multiple symmetrical synaptic contacts that generated inhibitory postsynaptic currents. This is remarkable considering that CINs represent a very small population of all accumbal neurons, and provide the primary source of cholinergic tone in the NAc. Brief activation of this projection was sufficient to halt the spontaneous activity of NAc CINs, resembling the pause recorded in animals learning stimulus-outcome associations. Indeed, we found that forcing CINs to pause in behaving mice enhanced discrimination of a motivationally important stimulus that had been associated with an aversive outcome. Our results demonstrate that VTA GABA projection neurons, through their selective targeting of accumbal CINs, provide a novel route through which the VTA communicates saliency to the NAc. VTA GABA projection neurons thus emerge as orchestrators of dopaminergic and cholinergic modulation in the NAc.

Neural bases for addictive properties of benzodiazepines.

Benzodiazepines are widely used in clinics and for recreational purposes, but will lead to addiction in vulnerable individuals. Addictive drugs increase the levels of dopamine and also trigger long-lasting synaptic adaptations in the mesolimbic reward system that ultimately may induce the pathological behaviour. The neural basis for the addictive nature of benzodiazepines, however, remains elusive. Here we show that benzodiazepines increase firing of dopamine neurons of the ventral tegmental area through the positive modulation of GABA(A) (gamma-aminobutyric acid type A) receptors in nearby interneurons. Such disinhibition, which relies on alpha1-containing GABA(A) receptors expressed in these cells, triggers drug-evoked synaptic plasticity in excitatory afferents onto dopamine neurons and underlies drug reinforcement. Taken together, our data provide evidence that benzodiazepines share defining pharmacological features of addictive drugs through cell-type-specific expression of alpha1-containing GABA(A) receptors in the ventral tegmental area. The data also indicate that subunit-selective benzodiazepines sparing alpha1 may be devoid of addiction liability.

Firing modes of dopamine neurons drive bidirectional GIRK channel plasticity.

G-protein-coupled inwardly rectifying potassium (GIRK) channels contribute to the resting membrane potential of many neurons, including dopamine (DA) neurons in the ventral tegmental area (VTA). VTA DA neurons are bistable, firing in two modes: one characterized by bursts of action potentials, the other by tonic firing at a lower frequency. Here we provide evidence that these firing modes drive bidirectional plasticity of GIRK channel-mediated currents. In acute midbrain slices of mice, we observed that in vitro burst activation of VTA DA neurons potentiated GIRK currents whereas tonic firing depressed these currents. This plasticity was not specific to the metabotropic receptor activating the GIRK channels, as direct activation of GIRK channels by nonhydrolyzable GTP also potentiated the currents. The plasticity of GIRK currents required NMDA receptor and CaMKII activation, and involved protein trafficking through specific PDZ domains of GIRK2c and GIRK3 subunit isoforms. Prolonged tonic firing may thus enhance the probability to switch into burst-firing mode, which then potentiates GIRK currents and favors the return to baseline. In conclusion, activity-dependent GIRK channel plasticity may represent a slow destabilization process favoring the switch between the two firing modes of VTA DA neurons.

A Way Forward for Comprehensive Cancer Caregiver Support.

Family caregivers are integral to patient care. However, a combination of systemic forces places enormous pressure on family caregivers, while simultaneously devaluing them. Recently, more public attention has been paid to caregivers' importance, prevalence, and needs, generating supportive responses by government, employers, and the media. As of yet, there has not been a commensurate response by health care institutions. We identify four key challenges to building comprehensive cancer caregiver support and propose five necessary components for future programs that cancer centers and organizations can adopt. Comprehensive cancer caregiver support is attainable but national organizations need to lead the effort through standardization of guidelines and metrics for cancer centers.

Expanding Leadership and Professional Development Opportunities for Oncology Nurse Practitioners.

Nurse practitioner (NP) involvement in professional organizations improves clinical practice, patient outcomes, and health care policy. Results of a survey for a local professional nursing organization showed a need for more NP-level education and NP mentorship and leadership training. Findings were applied to develop a leadership initiative through an NP-led continuing education program. At the conclusion of the program, NP presenters completed a survey. The NP presenters agreed that participating in this program and the mentoring that was provided helped them prepare for their sessions, improve their leadership skills, and prepare for additional speaking engagements. Additionally, each session's attendees completed evaluation surveys. Results from program attendees indicated a high level of agreement about meeting learning objectives in sessions and the effectiveness of the NP presenters. This innovative program may be modeled across a variety of nursing specialties, settings, and organizations to enhance NP professional development and support nursing-led continuing education. [J Contin Educ Nurs. 2024;55(2):94-100.].

Positive emotions co-experienced with strangers and acquaintances predict COVID-19 vaccination intentions through prosocial tendencies.

BACKGROUND: The efficacy of vaccination depends on its widespread adoption, making vaccine uptake not just a personal health behavior but also a prosocial one. Previous research has shown that everyday moments of co-experienced positive emotions (positivity resonance) are associated with higher prosocial tendencies, and these moments, in turn, prospectively predict people's pandemic hygiene behaviors. Yet, limited research has explored how moments of positivity resonance may have predicted greater COVID-19 vaccine intentions during the early months of the pandemic. METHODS: We longitudinally surveyed a national U.S. sample across four weeks during the fall of 2020. We tested the hypothesis that positivity resonance with strangers and acquaintances indirectly predicts COVID-19 vaccine intentions, as statistically mediated by prosocial tendencies. We also aimed to replicate the indirect effects of positivity resonance on hygiene behaviors (such as mask wearing and hand washing), effects that have been demonstrated in previous research. RESULTS: In a pre-registered structural equation model, we found that perceived positivity resonance experienced with strangers and acquaintances prospectively predicted prosocial tendencies, which in turn amplified people's COVID-19 vaccine intentions (ß = 0.053) and hygiene behaviors - i.e., social distancing (ß = 0.032), mask wearing (ß = 0.027), hand washing (ß = 0.049). CONCLUSIONS: Understanding the effects of high-quality social interactions with strangers and acquaintances on vaccine intentions and hygiene behaviors is critical, particularly given the likelihood of emerging pandemics and novel vaccines. We discuss theoretical and practical implications related to perceived positivity resonance, prosocial tendencies, and vaccination uptake for novel vaccines.

Material, Psychological, and Behavioral Financial Hardship Among Lesbian, Gay, and Bisexual Cancer Survivors in the United States.

PURPOSE: Driven by anti-LGBTQ+ stigma, emerging literature suggests that lesbian, gay, and bisexual (LGB) cancer survivors experience financial hardship (FH) more frequently than heterosexual survivors. However, few studies have used nationally representative samples to estimate this inequity. METHODS: National Health Interview Survey data from 2019 to 2022 were pooled and weighted. Outcomes included material, psychological, and behavioral FH. The behavioral domain was further broken down into subdomains including medical care, prescription medications, and mental health care. Multivariable logit models controlling for a variety of factors were used to generate LGB and heterosexual predicted probabilities and differential effects for each FH outcome. Stratified estimates were generated by sex and age groups. RESULTS: A total of N = 374 LGB and N = 12,757 heterosexual cancer survivors were included in this analysis. In adjusted analyses, LGB cancer survivors had significantly higher material (19%, 95% CI, 15 to 24 v 12%, 95% CI, 11 to 13; P = .004), psychological (44%, 95% CI, 38 to 51 v 37%, 95% CI, 36 to 38; P = .035), and behavioral (23%, 95% CI, 18 to 28 v 13%, 95% CI, 13 to 14; P < .0001) FH than heterosexual survivors. LGB cancer survivors also had higher medical behavioral (11%, 95% CI, 7 to 15 v 7%, 95% CI, 6 to 7; P = .030), prescription medication behavioral (14%, 95% CI, 10 to 19 v 10%, 95% CI, 9 to 10; P = .032), and mental health behavioral (9%, 95% CI, 6 to 13 v 3%, 95% CI, 3 to 4; P < .0001) FH than heterosexual survivors. Stratified estimates revealed young LGB cancer survivors had the highest probability of each outcome (material: 31%, 95% CI, 23 to 40; psychological: 58%, 95% CI, 50 to 66; behavioral: 45%, 95% CI, 36 to 53). CONCLUSION: In this nationally representative analysis, LGB cancer survivors experience substantial inequities in all FH outcomes. It is crucial that future FH interventional work should prioritize populations at the highest risk of FH, such as LGB cancer survivors.

Building on and tailoring to: Adapting a cancer caregiver psychoeducational intervention for rural settings.

INTRODUCTION: Rural cancer caregivers experience obstacles in accessing services, obtaining respite, and ensuring their care recipients receive quality care. These challenges warrant opportunities to participate in evidence-based behavioral intervention trials to fill support gaps. Adaptation to rural settings can facilitate appropriate fit, given higher caregiver service needs and unique challenges. We present findings from the adaptation process of a psychoeducational intervention designed to support cancer caregivers in rural settings. METHODS: We adapted Reblin's CARING intervention, designed for neuro-oncology, to target caregivers of rural cancer patients across cancer sites. First, we conducted formative work to determine the unmet social and supportive care needs rural cancer caregivers faced. We used the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS) to guide the modifications. To conduct the adaptation, we elicited feedback through qualitative interviews of seven caregivers and three cancer hospital staff and thematic analysis to inform intervention modifications. Our qualitative study was guided by the Consolidated Criteria for Reporting Qualitative Research (COREQ). RESULTS: Interviews revealed that service access was a pressing need, along with financial (e.g., treatment costs, employment challenges) and geographic barriers (e.g., distance to treatment, road conditions). We modified content, training, and context using the FRAME-IS steps. Changes enhanced fit through the following adaptations: changes to social support domains, session content, interventionist training, resource offerings, screening and recruitment processes, and virtual delivery. DISCUSSION: Challenges to establishing successful psychosocial oncology interventions may be improved through participant-centered approaches and implementation science. Additional systemic challenges, including lack of systematic documentation of caregivers, persist and may especially disadvantage under-represented and underserved groups, such as rural dwellers. The enCompass intervention is undergoing ongoing single-arm pilot of rural cancer patient/caregiver dyads targeting caregiver coping self-efficacy and patient/caregiver distress (Clinical Trials #NCT05828927).

Caring for Children in Relation to Financial Hardship, Advance Care Planning, and Genetic Testing Among Adolescent and Young Adults with Cancer.

Purpose: When a cancer diagnosis coincides with caring for children, it may influence the financial impacts of cancer and decisions to pursue advance care planning (ACP) or genetic testing. We examined associations between caring for children and financial hardship, ACP, and genetic testing among female adolescent and young adult (AYA) cancer survivors in North Carolina and California. Methods: Participants were diagnosed at ages 15-39 years with breast, melanoma, gynecologic, lymphoma, or thyroid cancer during 2004-2016. We estimated adjusted prevalence differences (aPDs) and ratios (aPRs) for each outcome by child caring status using marginal structural binomial regression models. Results: Among 1595 women ages 19-54 years at survey (median = 7 years since diagnosis), 819 (51.3%) reported that they were caring for children at diagnosis. Women caring for children had a higher prevalence of material financial hardship (e.g., medical debt; 30% vs. 21.9%; aPD = 9%, 95% confidence interval [CI]: 3 to 14; aPR = 1.39, 95% CI: 1.12 to 1.72) but similar levels of psychological financial hardship compared to noncaregivers. Women caring for children were more likely to complete ACPs (42.2% vs. 30.7%; aPD = 9%, 95% CI: 3 to 16; aPR = 1.30, 95% CI: 1.08 to 1.57). Among the 723 survivors of breast, endometrial, and ovarian cancer, the prevalence of genetic testing was higher among women caring for children (89%) than noncaregivers (81%); this difference was not statistically significant. Conclusion: Women caring for children at diagnosis may be at elevated risk for adverse financial outcomes and may benefit from additional financial navigation support. Childcare responsibilities may further complicate health decision-making for AYAs diagnosed with cancer.

Integrating Family Caregivers Into Cancer Care: Implementation of Evidence-Based Caregiver Protocols Into Gynecologic Oncology Practice.

PURPOSE: Family caregivers (CGs) of individuals with cancer are increasingly relied upon to provide long-term, sometimes intense care, although their integration into clinical cancer care remains minimal. The Caregiver Advocacy, Research, and Education (CARE) Center is a novel nurse-led academic-clinical partnership to support family CGs of individuals with gynecologic cancer. This study aims to describe the implementation of the Center protocols and report metrics of CG needs and Center support. MATERIALS AND METHODS: The Center's goals are to identify, assess, and provide tailored support to CGs. Initially, Center protocols included assessment of CGs' self-identified distress (distress thermometer, 0 = no distress to 10 = extreme distress) and needs (yes or no). Tailored support on the basis of CG distress was provided by in-person and remote staff who provided complementary, concurrent support based on CG need: evidence-based self-management guides, self-management support, referral to specialty services. Center documentation was analyzed to describe Center reach and CG distress. RESULTS: From November 2019 to June 2023, CGs (N = 1,250) were identified through referrals, new patient outreach, and inpatient visits. Seven hundred and six CGs (56.5%) were assessed through a needs-based assessment, and 515 (41.2%) CGs received tailored support. CGs were mostly men (53.0%) and the mean distress was 4.4/10 (standard deviation, 3.1). CG distress was moderately associated with CG needs including maintaining emotional (ρ = 0.40; P < .001) and physical (ρ = 0.31; P < .001) health and managing patient symptoms (ρ = 0.33; P < .001). CONCLUSION: Center protocols facilitate identification of high-need CGs within a cancer clinic. Future research will longitudinally evaluate the impact of Center protocols on CG and patient outcomes, incorporating updated assessment tools.

"A strong reason why I enjoy coming to work": Clinician acceptability of a palliative and supportive care intervention (PACT) for older adults with acute myeloid leukemia and their care partners.

INTRODUCTION: Studies about clinician acceptability of integrative palliative care interventions in the inpatient and outpatient cancer settings are limited. In this study, we examined clinician acceptability of a NIH-funded interdisciplinary PAlliative and Supportive Care inTervention (PACT) for older adults with acute myeloid leukemia (AML) and their care partners that transcends both inpatient and outpatient settings. MATERIALS AND METHODS: Data was collected using semi-structured interviews with clinicians who were directly involved in PACT. The domains of the Theoretical Framework of Acceptability were used to guide the qualitative analysis. RESULTS: The clinicians consisted of occupational therapists (37%), physical therapists (25%), registered nurses (25%), and a clinical rehabilitation manager (13%). Five themes were identified in the thematic analysis: (1) Emotions and affect towards the intervention, (2) Intervention coherence and self-efficacy, (3) Barriers, burden, and opportunity costs of delivering the intervention, (4) Usefulness and effectiveness of the intervention, and (5) Recommendations to improve intervention delivery. DISCUSSION: All clinicians found the PACT intervention highly acceptable and expressed the positive impact of the intervention on job fulfillment and satisfaction. Our findings provide evidence to inform the delivery and implementation of future large scale integrative palliative care intervention trials.

Piloting HealthScore: Feasibility and acceptability of a clinically integrated health coaching program for people living with cancer.

BACKGROUND: Cancer supportive care interventions often have limited generalizability, goal misalignment, and high costs. We developed and piloted a health coaching intervention, UNC HealthScore, in patients undergoing cancer treatment (ClinicalTrials.gov identifier NCT04923997). We present feasibility, acceptability, and preliminary outcome data. METHODS: HealthScore is a six-month, theory-based, multicomponent intervention delivered through participant-driven coaching sessions. For the pilot study, participants were provided a Fitbit, responded to weekly symptom and physical function digital surveys, and met with a health coach weekly to develop and monitor goals. Coaching notes were discussed in weekly interdisciplinary team meetings and provided back to the treating oncology team. Symptom alerts were monitored and triaged through a study resource nurse to relevant supportive care services. Feasibility was determined based on intervention enrollment and completion. Acceptability was based on satisfaction with coaching and Fitbit-wearing and was informed by semistructured exit interviews. Outcomes evaluated for signs of improvement included several PROMIS (Patient-Reported Outcomes Measurement Information System) measures, including the primary intervention target, physical function. RESULTS: From May 2020 to March 2022, 50 participants completed the single-arm pilot. Feasibility was high: 66% enrolled and 71% completed the full intervention. Participants reported an average of 4.8 and 4.7 (out of 5) on the acceptability of coaching calls and using the Fitbit, respectively. Physical function scores rose 3.1 points (SE = 1.1) from baseline to 3 months, and 4.3 (SE = 1.0) from baseline to 6 months, above established minimal clinically important difference (MCID). Improvements above MCID were also evident in anxiety and depression, and smaller improvements were demonstrated for emotional support, social isolation, cognitive function, symptom burden, and self-efficacy. DISCUSSION: HealthScore shows feasibility, acceptability, and promising preliminary outcomes. Randomized studies are underway to determine the efficacy of preserving physical function in patients with advanced cancer.

Zona incerta subpopulations differentially encode and modulate anxiety.

Despite recent clinical observations linking the zona incerta (ZI) to anxiety, little is known about whether and how the ZI processes anxiety. Here, we subject mice to anxious experiences and observe an increase in ZI c-fos­labeled neurons and single-cell calcium activity as well as an efficient effect of ZI infusion of diazepam, a classical anxiolytic drug. We further identify that somatostatin (SOM)­, calretinin (CR)­, and vesicular glutamate transporter-2 (Vglut2)­expressing cells display unique electrophysiological profiles; however, they similarly respond to anxiety-provoking stimuli and to diazepam. Optogenetic manipulations reveal that each of these ZI neuronal populations triggers specific anxiety-related behavioral phenotypes. Activation of SOM-expressing neurons induced anxiety, while photoactivation of CR-positive cells and photoinhibition of Vglut2-expressing neurons produce anxiolysis. Furthermore, activation of CR- and Vglut2-positive cells provokes rearing and jumps, respectively. Our findings provide the first experimental evidence that ZI subpopulations encode and modulate different components of anxiety.

Lateral ventral tegmental area GABAergic and glutamatergic modulation of conditioned learning.

The firing activity of dorso-medial-striatal-cholinergic interneurons (dmCINs) is a neural correlate of classical conditioning. Tonically active, they pause in response to salient stimuli, mediating acquisition of predictive cues/outcome associations. Cortical and thalamic inputs are typical of the rather limited knowledge about underlying circuitry contributing to this function. Here, we dissect the midbrain GABA and glutamate-to-dmCIN pathways and evaluate how they influence conditioned behavior. We report that midbrain neurons discriminate auditory cues and encode the association of a predictive stimulus with a footshock. Furthermore, GABA and glutamate cells form selective monosynaptic contacts onto dmCINs and di-synaptic ones via the parafascicular thalamus. Pathway-specific inhibition of each sub-circuit produces differential impairments of fear-conditioned learning. Finally, Vglut2-expressing cells discriminate between CSs although Vgat-positive neurons associate the predictive cue with the outcome. Overall, these data suggest that each component of the network carries information pertinent to sub-domains of the behavioral strategy.

Release of stem cells from quiescence reveals gliogenic domains in the adult mouse brain.

Quiescent neural stem cells (NSCs) in the adult mouse ventricular-subventricular zone (V-SVZ) undergo activation to generate neurons and some glia. Here we show that platelet-derived growth factor receptor beta (PDGFRß) is expressed by adult V-SVZ NSCs that generate olfactory bulb interneurons and glia. Selective deletion of PDGFRß in adult V-SVZ NSCs leads to their release from quiescence, uncovering gliogenic domains for different glial cell types. These domains are also recruited upon injury. We identify an intraventricular oligodendrocyte progenitor derived from NSCs inside the brain ventricles that contacts supraependymal axons. Together, our findings reveal that the adult V-SVZ contains spatial domains for gliogenesis, in addition to those for neurogenesis. These gliogenic NSC domains tend to be quiescent under homeostasis and may contribute to brain plasticity.