Current Best Practices for Analysis of Dendritic Spine Morphology and Number in Neurodevelopmental Disorder Research

Abstract

Quantitative methods for assessing neural anatomy have rapidly evolved in neuroscience and provide important insights into brain health and function. However, as new techniques develop, it is not always clear when and how each may be used to answer specific scientific questions posed. Dendritic spines, which are often indicative of synapse formation and neural plasticity, have been implicated across many brain regions in neurodevelopmental disorders as a marker for neural changes reflecting neural dysfunction or alterations. In this Perspective we highlight several techniques for staining, imaging, and quantifying dendritic spines as well as provide a framework for avoiding potential issues related to pseudoreplication. This framework illustrates how others may apply the most rigorous approaches. We consider the cost-benefit analysis of the varied techniques, recognizing that the most sophisticated equipment may not always be necessary for answering some research questions. Together, we hope this piece will help researchers determine the best strategy toward using the ever-growing number of techniques available to determine neural changes underlying dendritic spine morphology in health and neurodevelopmental disorders.

Effect of Human Infant Gut Microbiota on Mouse Behavior, Dendritic Complexity, and Myelination

“…Another question that remains is whether these structural changes have functional consequences not captured by our behavioral tests. Dendritic arbors receive most synaptic inputs while dendritic spines represent the most important parts of excitatory synapses in the hippocampus, neocortex, and other brain regions (90)(91)(92). Consequently, the alterations we observed could affect synaptic transmission and plasticity such that HUM1 mice have a more active PFC and nucleus accumbens than HUM2 animals.…”

Dysfunction of specific auditory fibers impacts cortical oscillations, driving an autism phenotype despite near‐normal hearing

“…Reduced cortical inhibition, leading to E/I imbalance in neuropsychiatric diseases, was associated with changes in GABAergic proteins and spine maturation patterns, for example, in the HC (e.g., 53–55 ).…”

Between neurons and networks: investigating mesoscale brain connectivity in neurological and psychiatric disorders

“…The image processing routine for analyzing dendritic spines involves a five-step pipeline: (i) data pre-processing as described before, (ii) spine location detection, (iii) segmentation to isolate them, (iv) quantification of morphological characteristics, and (v) classification or clustering based on their morphology ( Li et al, 2023 ).…”