What are the different types of neurons in the human brain?
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Types of Neurons in the Human Brain
Understanding the diversity of neurons in the human brain is crucial for comprehending its complex functions and susceptibility to various diseases. Neurons can be classified based on their morphology, molecular markers, connectivity, and functional properties. This article synthesizes recent research to provide an overview of the different types of neurons in the human brain.
Morphological Diversity of Neurons
Neurons exhibit a wide range of morphological features, which are essential for their classification. A comprehensive study identified 11 major projection neuron types with distinct morphological characteristics and corresponding transcriptomic identities. These types include various subtypes based on their axonal projections, dendritic structures, and regional specificity. For example, cortical layer 5 (L5) pyramidal neurons are divided into cortico-cortical (CC), cortico-subcortical (CS), and a newly identified cortico-cortical, non-striatal (CC-NS) subtype, each with unique connectivity and functional roles.
Molecular and Transcriptomic Classification
Single-nucleus RNA sequencing has revealed a highly diverse set of excitatory and inhibitory neuron types in the human cortex. These types are mostly sparse, with excitatory neurons being less layer-restricted than previously thought. In the human brain, 16 neuronal subtypes have been identified based on gene expression profiles, showing regional variations that define distinct cortical areas. This method allows for the identification of previously unknown neuronal subtypes and provides insights into their regional identity and transcriptomic heterogeneity.
Functional Classification of Neurons
Functional properties are another critical aspect of neuronal classification. Neurons can be grouped based on their roles in encoding sensory stimuli and their responses to various inputs. For instance, L5 CS neurons are more direction-selective and prefer faster stimuli compared to CC neurons, suggesting specialized roles in movement control and visual perception, respectively. Additionally, GABAergic interneurons in the human neocortex exhibit distinct morphoelectric properties, which are crucial for understanding their roles in neural circuits and cognitive functions.
Epigenetic Differences Between Neuronal Subtypes
Epigenetic modifications, such as DNA methylation, play a significant role in shaping and maintaining neuronal identity. Major differences in CpG, non-CpG, and hydroxymethylation (hCpG) have been observed between GABAergic interneurons and glutamatergic (GLU) projection neurons in the human prefrontal cortex. These epigenetic differences are linked to functional distinctions between neuronal subtypes and are enriched for schizophrenia risk loci, highlighting their importance in brain function and disease.
Evolutionary Perspective on Neuronal Diversity
Comparative studies across species have shown that the mammalian cerebral cortex is a mosaic of conserved and recently evolved neuron types. This evolutionary perspective helps reconcile observations on neural development, neuroanatomy, circuit wiring, and physiology, providing an integrated understanding of brain evolution. For example, homologous neuron types in humans and mice exhibit differences in proportions, laminar distributions, gene expression, and morphology, emphasizing the need for direct studies on human brain cells.
Conclusion
The human brain comprises a vast array of neuron types, each with unique morphological, molecular, functional, and epigenetic characteristics. Advances in high-throughput techniques, such as single-nucleus RNA sequencing and Patch-seq, have significantly enhanced our understanding of this diversity. These insights are crucial for unraveling the complexities of brain function and for developing targeted therapies for neurological diseases.
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Most relevant research papers on this topic
Morphological diversity of single neurons in molecularly defined cell types
Conserved cell types with divergent features in human versus mouse cortex
Neuronal cell-type classification: challenges, opportunities and the path forward
Three Types of Cortical Layer 5 Neurons That Differ in Brain-wide Connectivity and Function
Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain
Substantial DNA methylation differences between two major neuronal subtypes in human brain
Toward Functional Classification of Neuronal Types
From Cell Types to an Integrated Understanding of Brain Evolution: The Case of the Cerebral Cortex.
Signature morphoelectric properties of diverse GABAergic interneurons in the human neocortex
Spatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex
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