Circuit dynamics of the olfactory pathway during olfactory learning.
The olfactory system plays crucial roles in perceiving and interacting with their surroundings. Previous studies have deciphered basic odor perceptions, but how information processing in the olfactory system is associated with learning and memory is poorly understood. In this review, we summarize recent studies on the anatomy and functional dynamics of the mouse olfactory learning pathway, focusing on how neuronal circuits in the olfactory bulb (OB) and olfactory cortical areas integrate odor information in learning. We also highlight in vivo evidence for the role of the lateral entorhinal cortex (LEC) in olfactory learning. Altogether, these studies demonstrate that brain regions throughout the olfactory system are critically involved in forming and representing learned knowledge. The role of olfactory areas in learning and memory, and their susceptibility to dysfunction in neurodegenerative diseases, necessitate further research.
Zhang YJ
,Lee JY
,Igarashi KM
《Frontiers in Neural Circuits》
Dynamic Field Theory of Executive Function: Identifying Early Neurocognitive Markers.
In this Monograph, we explored neurocognitive predictors of executive function (EF) development in a cohort of children followed longitudinally from 30 to 54 months of age. We tested predictions of a dynamic field model that explains development in a benchmark measure of EF development, the dimensional change card sort (DCCS) task. This is a rule-use task that measures children's ability to switch between sorting cards by shape or color rules. A key developmental mechanism in the model is that dimensional label learning drives EF development. Data collection began in February 2019 and was completed in April 2022 on the Knoxville campus of the University of Tennessee. Our cohort included 20 children (13 female) all of whom were White (not Hispanic/Latinx) from an urban area in southern United States, and the sample annual family income distribution ranged from low to high (most families falling between $40,000 and 59,000 per year (note that we address issues of generalizability and the small sample size throughout the monograph)). We tested the influence of dimensional label learning on DCCS performance by longitudinally assessing neurocognitive function across multiple domains at 30 and 54 months of age. We measured dimensional label learning with comprehension and production tasks for shape and color labels. Simple EF was measured with the Simon task which required children to respond to images of a cat or dog with a lateralized (left/right) button press. Response conflict was manipulated in this task based on the spatial location of the stimulus which could be neutral (central), congruent, or incongruent with the spatial lateralization of the response. Dimensional understanding was measured with an object matching task requiring children to generalize similarity between objects that matched within the dimensions of color or shape. We first identified neural measures associated with performance and development on each of these tasks. We then examined which of these measures predicted performance on the DCCS task at 54 months. We measured neural activity with functional near-infrared spectroscopy across bilateral frontal, temporal, and parietal cortices. Our results identified an array of neurocognitive mechanisms associated with development within each domain we assessed. Importantly, our results suggest that dimensional label learning impacts the development of EF. Neural activation in left frontal cortex during dimensional label production at 30 months of age predicted EF performance at 54 months of age. We discussed these results in the context of efforts to train EF with broad transfer. We also discussed a new autonomy-centered EF framework. The dynamic field model on which we have motivated the current research makes decisions autonomously and various factors can influence the types of decisions that the model makes. In this way, EF is a property of neurocognitive dynamics, which can be influenced by individual factors and contextual effects. We also discuss how this conceptual framework can generalize beyond the specific example of dimensional label learning and DCCS performance to other aspects of EF and how this framework can help to understand how EF unfolds in unique individual, cultural, and contextual factors. Measures of EF during early childhood are associated with a wide range of development outcomes, including academic skills and quality of life. The hope is that broad aspects of development can be improved by implementing interventions aimed at facilitating EF development. However, this promise has been largely unrealized. Previous work on EF development has been limited by a focus on EF components, such as inhibition, working memory, and switching. Similarly, intervention research has focused on practicing EF tasks that target these specific components of EF. While performance typically improves on the practiced task, improvement rarely generalizes to other EF tasks or other developmental outcomes. The current work is unique because we looked beyond EF itself to identify the lower-level learning processes that predict EF development. Indeed, the results of this study identify the first learning mechanism involved in the development of EF. Although the work here provides new targets for interventions in future work, there are also important limitations. First, our sample is not representative of the underlying population of children in the United States under the age of 5. This is a problem in much of the existing developmental cognitive neuroscience research. We discussed challenges to the generalizability of our findings to the population at large. This is particularly important given that our theory is largely contextual, suggesting that children's unique experiences with learning labels for visual dimensions will impact EF development. Second, we identified a learning mechanism to target in future intervention research; however, it is not clear whether such interventions would benefit all children or how to identify children who would benefit most from such interventions. We also discuss prospective lines of research that can address these limitations, such as targeting families that are typically underrepresented in research, expanding longitudinal studies to examine longer term outcomes such as school-readiness and academic skills, and using the dynamic field (DF) model to systematically explore how exposure to objects and labels can optimize the neural representations underlying dimensional label learning. Future work remains to understand how such learning processes come to define the contextually and culturally specific skills that emerge over development and how these skills lay the foundation for broad developmental trajectories.
McCraw A
,Sullivan J
,Lowery K
,Eddings R
,Heim HR
,Buss AT
... -
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Early adversity causes sex-specific deficits in perforant pathway connectivity and contextual memory in adolescent mice.
Early life adversity impairs hippocampal development and function across diverse species. While initial evidence indicated potential variations between males and females, further research is required to validate these observations and better understand the underlying mechanisms contributing to these sex differences. Furthermore, most of the preclinical work in rodents was performed in adult males, with only few studies examining sex differences during adolescence when such differences appear more pronounced. To address these concerns, we investigated the impact of limited bedding (LB), a mouse model of early adversity, on hippocampal development in prepubescent and adolescent male and female mice.
RNA sequencing, confocal microscopy, and electron microscopy were used to evaluate the impact of LB and sex on hippocampal development in prepubescent postnatal day 17 (P17) mice. Additional studies were conducted on adolescent mice aged P29-36, which included contextual fear conditioning, retrograde tracing, and ex vivo diffusion magnetic resonance imaging (dMRI).
More severe deficits in axonal innervation and myelination were found in the perforant pathway of prepubescent and adolescent LB males compared to LB female littermates. These sex differences were due to a failure of reelin-positive neurons located in the lateral entorhinal cortex (LEC) to innervate the dorsal hippocampus via the perforant pathway in males, but not LB females, and were strongly correlated with deficits in contextual fear conditioning.
LB impairs the capacity of reelin-positive cells located in the LEC to project and innervate the dorsal hippocampus in LB males but not female LB littermates. Given the critical role that these projections play in supporting normal hippocampal function, a failure to establish proper connectivity between the LEC and the dorsal hippocampus provides a compelling and novel mechanism to explain the more severe deficits in myelination and contextual freezing found in adolescent LB males.
Islam R
,White JD
,Arefin TM
,Mehta S
,Liu X
,Polis B
,Giuliano L
,Ahmed S
,Bowers C
,Zhang J
,Kaffman A
... -
《Biology of Sex Differences》