Two photon interrogation of hippocampal subregions CA1 and CA3 during spatial behaviour

The hippocampus is crucial for spatial navigation and episodic memory formation. Hippocampal place cells exhibit spatially selective activity within an environment and form the neural basis of a cognitive map of space which supports these mnemonic functions. Hebb’s (1949) postulate regarding the creation of cell assemblies is seen as the pre-eminent model of learning in neural systems. Investigating changes to the hippocampal representation of space during an animal’s exploration of its environment provides an opportunity to observe Hebbian learning at the population and single cell level. When exploring new environments animals form spatial memories that are updated with experience and retrieved upon re-exposure to the same environment, but how this is achieved by different subnetworks in hippocampal CA1 and CA3, and how these circuits encode distinct memories of similar objects and events remains unclear. To test these ideas, we developed an experimental strategy and detailed protocols for simultaneously recording from CA1 and CA3 populations with 2P imaging. We also developed a novel all-optical protocol to simultaneously activate and record from ensembles of CA3 neurons. We used these approaches to show that targeted activation of CA3 neurons results in an increasing excitatory amplification seen only in CA3 cells when stimulating other CA3 cells, and not in CA1, perhaps reflecting the greater number of recurrent connections in CA3. To probe hippocampal spatial representations, we titrated input to the network by morphing VR environments during spatial navigation to assess the local CA3 as well as downstream CA1 responses. To this end, we found CA1 and CA3 neural population responses behave nonlinearly, consistent with attractor dynamics associated with the two stored representations. We interpret our findings as supporting classic theories of Hebbian learning and as the beginning of uncovering the relationship between hippocampal neural circuit activity and the computations implemented by their dynamics. Establishing this relationship is paramount to demystifying the neural underpinnings of cognition

Infants' visual sustained attention is higher during joint play than solo play: is this due to increased endogenous attention control or exogenous stimulus capture?

Previous research has suggested that when a social partner, such as a parent, pays attention to an object, this increases the attention that infants pay to that object during spontaneous, naturalistic play. There are two contrasting reasons why this might be: first, social context may influence increases in infants' endogenous (voluntary) attention control; second, social settings may offer increased opportunities for exogenous attentional capture. To differentiate these possibilities, we compared 12-month-old infants' naturalistic attention patterns in two settings: Solo Play and Joint Play with a social partner (the parent). Consistent with previous research, we found that infants' look durations toward play objects were longer during Joint Play, and that moments of inattentiveness were fewer, and shorter. Follow-up analyses, conducted to differentiate the two above-proposed hypotheses, were more consistent with the latter hypothesis. We found that infants' rate of change of attentiveness was faster during Joint Play than Solo Play, suggesting that internal attention factors, such as attentional inertia, may influence looking behaviour less during Joint Play. We also found that adults' attention forwards-predicted infants' subsequent attention more than vice versa, suggesting that adults' behaviour may drive infants' behaviour. Finally, we found that mutual gaze did not directly facilitate infant attentiveness. Overall, our results suggest that infants spend more time attending to objects during Joint Play than Solo Play, but that these differences are more likely attributable to increased exogenous attentional scaffolding from the parent during social play, rather than to increased endogenous attention control from the infant

Infants' visual sustained attention is higher during joint play than solo play: is this due to increased endogenous attention control or exogenous stimulus capture?

Previous research has suggested that when a social partner, such as a parent, pays attention to an object, this increases the attention that infants pay to that object during spontaneous, naturalistic play. There are two contrasting reasons why this might be: first, social context may influence increases in infants' endogenous (voluntary) attention control; second, social settings may offer increased opportunities for exogenous attentional capture. To differentiate these possibilities, we compared 12‐month‐old infants' naturalistic attention patterns in two settings: Solo Play and Joint Play with a social partner (the parent). Consistent with previous research, we found that infants' look durations toward play objects were longer during Joint Play, and that moments of inattentiveness were fewer, and shorter. Follow‐up analyses, conducted to differentiate the two above‐proposed hypotheses, were more consistent with the latter hypothesis. We found that infants' rate of change of attentiveness was faster during Joint Play than Solo Play, suggesting that internal attention factors, such as attentional inertia, may influence looking behaviour less during Joint Play. We also found that adults' attention forwards‐predicted infants' subsequent attention more than vice versa, suggesting that adults' behaviour may drive infants' behaviour. Finally, we found that mutual gaze did not directly facilitate infant attentiveness. Overall, our results suggest that infants spend more time attending to objects during Joint Play than Solo Play, but that these differences are more likely attributable to increased exogenous attentional scaffolding from the parent during social play, rather than to increased endogenous attention control from the infant

All-optical interrogation of neural circuits in behaving mice

Recent advances combining two-photon calcium imaging and two-photon optogenetics with computer-generated holography now allow us to read and write the activity of large populations of neurons in vivo at cellular resolution and with high temporal resolution. Such 'all-optical' techniques enable experimenters to probe the effects of functionally defined neurons on neural circuit function and behavioral output with new levels of precision. This greatly increases flexibility, resolution, targeting specificity and throughput compared with alternative approaches based on electrophysiology and/or one-photon optogenetics and can interrogate larger and more densely labeled populations of neurons than current voltage imaging-based implementations. This protocol describes the experimental workflow for all-optical interrogation experiments in awake, behaving head-fixed mice. We describe modular procedures for the setup and calibration of an all-optical system (~3 h), the preparation of an indicator and opsin-expressing and task-performing animal (~3-6 weeks), the characterization of functional and photostimulation responses (~2 h per field of view) and the design and implementation of an all-optical experiment (achievable within the timescale of a normal behavioral experiment; ~3-5 h per field of view). We discuss optimizations for efficiently selecting and targeting neuronal ensembles for photostimulation sequences, as well as generating photostimulation response maps from the imaging data that can be used to examine the impact of photostimulation on the local circuit. We demonstrate the utility of this strategy in three brain areas by using different experimental setups. This approach can in principle be adapted to any brain area to probe functional connectivity in neural circuits and investigate the relationship between neural circuit activity and behavior

Do Helpful Mothers Help? Effects of Maternal Scaffolding and Infant Engagement on Cognitive Performance.

Infants are highly social and much early learning takes place in a social context during interactions with caregivers. Previous research shows that social scaffolding - responsive parenting and joint attention - can confer benefits for infants' long-term development and learning. However, little previous research has examined whether dynamic (moment-to-moment) adaptations in adults' social scaffolding are able to produce immediate effects on infants' performance. Here we ask whether infants' success on an object search task is more strongly influenced by maternal behavior, including dynamic changes in response behavior, or by fluctuations in infants' own engagement levels. Thirty-five mother-infant dyads (infants aged 10.8 months, on average) participated in an object search task that was delivered in a naturalistic manner by the child's mother. Measures of maternal responsiveness (teaching duration; sensitivity) and infant engagement (engagement score; visual attention) were assessed. Mothers varied their task delivery trial by trial, but neither measure of maternal responsiveness significantly predicted infants' success in performing the search task. Rather, infants' own level of engagement was the sole significant predictor of accuracy. These results indicate that while parental scaffolding is offered spontaneously (and is undoubtedly crucial for development), in this context children's endogenous engagement proved to be a more powerful determinant of task success. Future work should explore this interplay between parental and child-internal factors in other learning and social contexts

Certified to make a difference’: the motivation and perceptions of newly qualified early years teachers in England

The last 20 years have brought numerous workforce reforms to the early years sector, enacted in the name of professionalisation, including the recent introduction of a new postgraduate qualification, the Early Years Teacher Status. This article features data from interviews with 22 participants who had just completed this award and situates their views in the relevant policy context and alongside a discussion of what it means to professionalise the early years sector and create a graduate led workforce. The data support findings from similar studies of Early Years Professionals, namely that the interviewees are passionate about working with young children. They view the sector as in need of change, and themselves as potential leaders and agents of change. The participants endorse the view that up-skilling the workforce is essential to the professionalisation of the sector and improving the quality of early years educatio

Erratum to: CASPER plus (CollAborative care in screen-positive EldeRs with major depressive disorder): study protocol for a randomised controlled trial

Published onlinePUBLISHED ERRATUMThe original article is available at http://hdl.handle.net/10871/18985.n/

Identifying perinatal depression with case-finding instruments : a mixed-methods study (BaBY PaNDA – Born and Bred in Yorkshire PeriNatal Depression Diagnostic Accuracy)

Background: Perinatal depression is well recognised as a mental health condition but < 50% of cases are identified in routine practice. A case-finding strategy using the Whooley questions is currently recommended by the National Institute for Health and Care Excellence. Objectives: To determine the diagnostic accuracy, acceptability and cost-effectiveness of the Whooley questions and the Edinburgh Postnatal Depression Scale (EPDS) to identify perinatal depression. Design: A prospective diagnostic accuracy cohort study, with concurrent qualitative and economic evaluations. Setting: Maternity services in England. Participants: A total of 391 pregnant women. Main outcome measures: Women completed the Whooley questions, EPDS and a diagnostic reference standard (Clinical Interview Schedule – Revised) during pregnancy (20 weeks) and postnatally (3–4 months). Qualitative interviews were conducted with health professionals (HPs) and a subsample of women. Results: Diagnostic accuracy results: depression prevalence rates were 10.3% during pregnancy and 10.5% postnatally. The Whooley questions and EPDS (cut-off point of ≥ 10) performed reasonably well, with comparable sensitivity [pregnancy: Whooley questions 85.0%, 95% confidence interval (CI) 70.2% to 94.3%; EPDS 82.5%, 95% CI 67.2% to 92.7%; postnatally: Whooley questions 85.7%, 95% CI 69.7% to 95.2%; EPDS 82.9%, 95% CI 66.4% to 93.4%] and specificity (pregnancy: Whooley questions 83.7%, 95% CI 79.4% to 87.4%; EPDS 86.6%, 95% CI 82.5% to 90.0%; postnatally: Whooley questions 80.6%, 95% CI 75.7% to 84.9%; EPDS 87.6%, 95% CI 83.3% to 91.1%). Diagnostic accuracy of the EPDS (cut-off point of ≥ 13) was poor at both time points (pregnancy: sensitivity 45%, 95% CI 29.3% to 61.5%, and specificity 95.7%, 95% CI 93.0% to 97.6%; postnatally: sensitivity 62.9%, 95% CI 44.9% to 78.5%, and specificity 95.7%, 95% CI 92.7% to 97.7%). Qualitative evaluation: women and HPs were supportive of screening/case-finding for perinatal depression. The EPDS was preferred to the Whooley questions by women and HPs, mainly because of its ‘softer’ wording. Whooley question 1 was thought to be less acceptable, largely because of the terms ‘depressed’ and ‘hopeless’, leading to women not revealing their depressive symptoms. HPs identified a ‘patient-centred’ environment that focused on the mother and baby to promote discussion about mental health. Cost-effectiveness results: screening/case-finding using the Whooley questions or the EPDS alone was not the most cost-effective strategy. A two-stage strategy, ‘Whooley questions followed by the Patient Health Questionnaire’ (a measure assessing depression symptomatology), was the most cost-effective strategy in the range between £20,000 and £30,000 per quality-adjusted life-year in both the prenatal and postnatal decision models. Limitations: Perinatal depression diagnosis was not cross-referenced with women’s medical records so the proportion of new cases identified is unknown. The clinical effectiveness and cost-effectiveness of screening/case-finding strategies was not assessed as part of a randomised controlled trial. Conclusions: The Whooley questions and EPDS had acceptable sensitivity and specificity, but their use in practice might be limited by low predictive value and variation in their acceptability. A two-stage strategy was more cost-effective than single-stage strategies. Neither case-finding instrument met National Screening Committee criteria. Future work: The yield of screening/case-finding should be established with reference to health-care records. The clinical effectiveness and cost-effectiveness of screening/case-finding for perinatal depression needs to be tested in a randomised controlled trial. Funding: The National Institute for Health Research Health Services and Delivery Research programme

Do Helpful Mothers Help? Effects of Maternal Scaffolding and Infant Engagement on Cognitive Performance.

Infants are highly social and much early learning takes place in a social context during interactions with caregivers. Previous research shows that social scaffolding - responsive parenting and joint attention - can confer benefits for infants' long-term development and learning. However, little previous research has examined whether dynamic (moment-to-moment) adaptations in adults' social scaffolding are able to produce immediate effects on infants' performance. Here we ask whether infants' success on an object search task is more strongly influenced by maternal behavior, including dynamic changes in response behavior, or by fluctuations in infants' own engagement levels. Thirty-five mother-infant dyads (infants aged 10.8 months, on average) participated in an object search task that was delivered in a naturalistic manner by the child's mother. Measures of maternal responsiveness (teaching duration; sensitivity) and infant engagement (engagement score; visual attention) were assessed. Mothers varied their task delivery trial by trial, but neither measure of maternal responsiveness significantly predicted infants' success in performing the search task. Rather, infants' own level of engagement was the sole significant predictor of accuracy. These results indicate that while parental scaffolding is offered spontaneously (and is undoubtedly crucial for development), in this context children's endogenous engagement proved to be a more powerful determinant of task success. Future work should explore this interplay between parental and child-internal factors in other learning and social contexts