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An emergent neural coactivity code for dynamic memory.
Neural correlates of external variables provide potential internal codes that guide an animal's behavior. Notably, first-order features of neural activity, such as single-neuron firing rates, have been implicated in encoding information. However, the extent to which higher-order features, such as multineuron coactivity, play primary roles in encoding information or secondary roles in supporting single-neuron codes remains unclear. Here, we show that millisecond-timescale coactivity among hippocampal CA1 neurons discriminates distinct, short-lived behavioral contingencies. This contingency discrimination was unrelated to the tuning of individual neurons, but was instead an emergent property of their coactivity. Contingency-discriminating patterns were reactivated offline after learning, and their reinstatement predicted trial-by-trial memory performance. Moreover, optogenetic suppression of inputs from the upstream CA3 region during learning impaired coactivity-based contingency information in the CA1 and subsequent dynamic memory retrieval. These findings identify millisecond-timescale coactivity as a primary feature of neural firing that encodes behaviorally relevant variables and supports memory retrieval.
Integrating new memories into the hippocampal network activity space.
By investigating the topology of neuronal co-activity, we found that mnemonic information spans multiple operational axes in the mouse hippocampus network. High-activity principal cells form the core of each memory along a first axis, segregating spatial contexts and novelty. Low-activity cells join co-activity motifs across behavioral events and enable their crosstalk along two other axes. This reveals an organizational principle for continuous integration and interaction of hippocampal memories.
A Hippocampus-Accumbens Tripartite Neuronal Motif Guides Appetitive Memory in Space.
Retrieving and acting on memories of food-predicting environments are fundamental processes for animal survival. Hippocampal pyramidal cells (PYRs) of the mammalian brain provide mnemonic representations of space. Yet the substrates by which these hippocampal representations support memory-guided behavior remain unknown. Here, we uncover a direct connection from dorsal CA1 (dCA1) hippocampus to nucleus accumbens (NAc) that enables the behavioral manifestation of place-reward memories. By monitoring neuronal ensembles in mouse dCA1→NAc pathway, combined with cell-type selective optogenetic manipulations of input-defined postsynaptic neurons, we show that dCA1 PYRs drive NAc medium spiny neurons and orchestrate their spiking activity using feedforward inhibition mediated by dCA1-connected parvalbumin-expressing fast-spiking interneurons. This tripartite cross-circuit motif supports spatial appetitive memory and associated NAc assemblies, being independent of dorsal subiculum and dispensable for both spatial novelty detection and reward seeking. Our findings demonstrate that the dCA1→NAc pathway instantiates a limbic-motor interface for neuronal representations of space to promote effective appetitive behavior.
Optogenetic Methods to Study Lateralized Synaptic Function
This volume explores both simple and sophisticated techniques used in the study of different types of lateralization of brain and behavior.
Archaerhodopsin Selectively and Reversibly Silences Synaptic Transmission through Altered pH.
Tools that allow acute and selective silencing of synaptic transmission in vivo would be invaluable for understanding the synaptic basis of specific behaviors. Here, we show that presynaptic expression of the proton pump archaerhodopsin enables robust, selective, and reversible optogenetic synaptic silencing with rapid onset and offset. Two-photon fluorescence imaging revealed that this effect is accompanied by a transient increase in pH restricted to archaerhodopsin-expressing boutons. Crucially, clamping intracellular pH abolished synaptic silencing without affecting the archaerhodopsin-mediated hyperpolarizing current, indicating that changes in pH mediate the synaptic silencing effect. To verify the utility of this technique, we used trial-limited, archaerhodopsin-mediated silencing to uncover a requirement for CA3-CA1 synapses whose afferents originate from the left CA3, but not those from the right CA3, for performance on a long-term memory task. These results highlight optogenetic, pH-mediated silencing of synaptic transmission as a spatiotemporally selective approach to dissecting synaptic function in behaving animals.
Synaptic Plasticity and Memory: New Insights from Hippocampal Left-Right Asymmetries.
All synapses are not the same. They differ in their morphology, molecular constituents, and malleability. A striking left-right asymmetry in the distribution of different types of synapse was recently uncovered at the CA3-CA1 projection in the mouse hippocampus, whereby afferents from the CA3 in the left hemisphere innervate small, highly plastic synapses on the apical dendrites of CA1 pyramidal neurons, whereas those originating from the right CA3 target larger, more stable synapses. Activity-dependent modification of these synapses is thought to participate in circuit formation and remodeling during development, and further plastic changes may support memory encoding in adulthood. Therefore, exploiting the CA3-CA1 asymmetry provides a promising opportunity to investigate the roles that different types of synapse play in these fundamental properties of the CNS. Here we describe the discovery of these segregated synaptic populations in the mouse hippocampus, and discuss what we have already learnt about synaptic plasticity from this asymmetric arrangement. We then propose models for how the asymmetry could be generated during development, and how the adult hippocampus might use these distinct populations of synapses differentially during learning and memory. Finally, we outline the potential implications of this left-right asymmetry for human hippocampal function, as well as dysfunction in memory disorders such as Alzheimer's disease.
Harmonising flavours: How arousing music and sound influence food perception and emotional responses
This study aims to provide a novel understanding of how music and sound varying in arousal can affect temporal changes in food perception and the corresponding emotional responses, measured through both subjective and objective (i.e., electrophysiological) methods. Exciting conditions are associated with low valence and high arousal, whereas calm conditions are associated with high valence and low arousal. Calm music (CM), calm sound (CS), and a combination of calm music and sound (CMCS) evoked emotions such as joy, relaxation, calmness, pleasantness, and at ease, and were correlated with the perception of sweetness and creaminess. Conversely, exciting music (EM) increased arousal, evoked emotions such as, activity, enthusiasm, energy, and excitement, and amplified the perception of roasted and bitter flavours. Exciting sounds (ES) and combined exciting music and exciting sound (EMES) conditions were positively correlated with anxiety, fatigue, unease, unhappiness, difficulty concentrating, irritation, and restlessness, as well as enhancing the perception of roasted and bitter flavours. Furthermore, the EM and EMES conditions gave rise to significantly higher skin conductance and respiration rate, with corresponding correlations with the perception of roasted and bitter flavours. The ES and EMES conditions demonstrated significantly higher heart rate and respiration rate. The CM condition showed significantly higher heart rate and emotional responses while the CS condition showed significantly higher skin conductance. The findings of this study indicate that sensory attributes are closely associated with the emotions and physiological responses evoked when consuming ice cream under different music and sound conditions.
Audiovisual Associations in Saint-Saëns’ Carnival of the Animals: A Cross-Cultural Investigation on the Role of Timbre
Several studies have investigated crossmodal associations involving audiovisual stimuli. To date, however, far fewer studies have explored the relationship between musical timbre and visual features (e.g., soft/harsh timbres with blue/red colours). To fill this gap in the literature, 249 participants were invited to judge the match between different coloured images and musical excerpts. The images depicted seven characters from Saint-Saëns’ “Carnival of the Animals”; the audio stimuli consisted of the music the composer created to represent each character. To test the effect of timbre and culture, the audio stimuli were presented either in the original orchestral version or in the piano transcription, while the participants were recruited from various countries, encompassing both Western and non-Western nationalities. The results demonstrate that timbre influences crossmodal associations between musical excerpts and drawings, while these associations remain consistent across cultures, languages, and levels of musical background.
Adopting Quality for School Readiness (AQSR): A Heuristic Framework using Recommended Practice and Professional Knowledge to Support Oral Language in Multilingual Classrooms
Quality oral language interventions support children’s readiness for formal literacy instruction and yet a framework for multilingual classrooms is not available. To address this gap, we drew on the empirical literature on linguistically diverse learners, classroom linguistic environments, and usage-based theories to identify principles for recommended pedagogical practices. We next examined how teachers explained their oral language teaching and what they said after delivering an intervention based on recommended practice. Using a reflexive approach to qualitative interview and questionnaire data, we found some convergence but also areas of limited overlap between recommended practice and teacher professional knowledge. Supporting child talk was seen to serve a motivational-affective purpose more than the cognitive-linguistic purposes implicit in research-informed recommended practices. Based on insights from specialized literature and distillations of professional knowledge, we propose a heuristic framework named Adopting Quality for School Readiness (AQSR). We also discuss uses for the AQSR framework and outstanding questions for future research.
Feasibility of an undergraduate academic fellowship in global health system development.
BACKGROUND: Despite increasing student interest in global health, undergraduate opportunities remain limited and often lack practical, multidisciplinary experiences. To address professional gaps for future healthcare professionals and global health workers, it is crucial to incorporate resource management, business practices, and leadership into undergraduate volunteer service-learning programs. METHODS: Lay First Responders (LFR) International's Fellowship Program in Emergency Medical Care and Innovation (ECMI) trains undergraduates to develop community-based emergency medical services in low- and middle-income countries, focusing on global capacity building, service leadership, and cultural competency. The year-long program guides fellows through a three-stage process of skill-development, design, and project implementation. The curriculum encompasses four main educational components: (1) professional development and networking, (2) global health education, (3) scientific research, and (4) internationally engaged collaboration. Program assessment was conducted through thematic analysis of open-ended survey responses from fellows at the beginning and end of their fellowship year. RESULTS: Since 2019, 22 fellows have completed the program, acquiring skills in research, teaching, and writing publications and grants. Surveys of the 2022 and 2023 cohorts revealed that all nine participants accomplished their intended goals during the fellowship, with over half expressing a desire to continue working with LFR International. The program's success is further evidenced by the fellows contributing to 17 academic outputs, securing $31,000 in funding, and their placement in advanced degree programs. CONCLUSIONS: The EMCI Fellowship has been well received and effective in addressing gaps in global health education. This model could be replicated by comparable global health non-governmental organizations to implement programs while immersing undergraduate students in hands-on international collaboration and operational management experiences. Future development should expand fellowship concentrations to additional global health fields and assess the long-term impacts of the program.
Quantifying CIE alpha-opic signals in the indoor built environment
As humans spend more time in mixed-illuminant “built” environments, it is important to quantify how light in indoor spaces differs from naturalistic scenes. Previous studies have quantified light across many natural environments and shown regularities in the chromatic variation across different seasons, times of day, and weather patterns. This study measures light in a typical mixed-illuminant office space in the northern hemisphere (51.76°N, −1.27∘W) and finds that it shares some regularities of chromatic variation with naturalistic scenes. In this dataset, such regularities are primarily conveyed through outdoor light entering through east- and north-facing windows and reflected by surfaces inside the office, rather than by light directly imaged through the north-facing window that was visible in the camera field-of-view. Built environments that combine natural daylight and artificial light to create mixed-illuminant spaces can share many of the statistical regularities that have been found in natural environments.