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 identities1. 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 roles4.
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 thought2. In the human brain, 16 neuronal subtypes have been identified based on gene expression profiles, showing regional variations that define distinct cortical areas5. 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, respectively4. Additionally, GABAergic interneurons in the human neocortex exhibit distinct morphoelectric properties, which are crucial for understanding their roles in neural circuits and cognitive functions9.
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 cortex6. 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 evolution8. 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 cells2.
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
Single-cell morphological diversity in neurons reveals diverse ways in which different cell types and their individual members contribute to the configuration and function of their circuits.
Rigorous Journal
Highly CitedConserved cell types with divergent features in human versus mouse cortex
Human cortex reveals well-conserved cellular architecture and homologous cell types, but also exhibits extensive differences in proportions, laminar distributions, gene expression, and morphology compared to mouse brain.
In Vitro Study
Very Rigorous JournalHighly CitedNeuronal cell-type classification: challenges, opportunities and the path forward
Neuronal classification is crucial for understanding brain circuits, but faces technical and conceptual challenges.
Highly CitedThree Types of Cortical Layer 5 Neurons That Differ in Brain-wide Connectivity and Function
Cortical layer 5 neurons have distinct roles in visual perception and movement control, with CS neurons integrating information and generating responses more relevant to movement control.
In Vitro StudyHighly CitedNeuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain
Single-nucleus RNA sequencing identifies 16 neuronal subtypes and reveals regional identity and transcriptomic heterogeneity within the human brain.
Highly CitedSubstantial DNA methylation differences between two major neuronal subtypes in human brain
DNA methylation differences between GABA and glutamatergic neurons in the human brain suggest that functional differences between neuronal subtypes are linked to their epigenetic specification.
In Vitro StudyHighly CitedFrom Cell Types to an Integrated Understanding of Brain Evolution: The Case of the Cerebral Cortex.
Comparing neuron types across species, such as mammals, reptiles, and birds, helps integrate observations on neural development, neuroanatomy, circuit wiring, and physiology for an integrated understanding of brain evolution.
Signature morphoelectric properties of diverse GABAergic interneurons in the human neocortex
Patch-seq sampling reveals diverse morphoelectric properties and cellular differences in human neocortical GABAergic interneurons, aiding in understanding their role in cognitive function and disease.
In Vitro StudySpatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex
The developing human brain's cortex is shaped by topographical, typological, and temporal hierarchies, with distinct excitatory lineages emerging in rostral and caudal cerebral cortex.
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