Synaptic Trimming Explanation:
Synaptic pruning, a natural process that begins in early childhood, plays a crucial role in the development of the brain. This process eliminates excess synapses and neurons to refine neural circuits, ensuring the brain operates efficiently.
Research indicates that impaired or dysfunctional synaptic pruning contributes to the pathophysiology of both schizophrenia and autism spectrum disorder (ASD). In schizophrenia, disruptions in neurodevelopment and synaptic pruning have been linked to symptoms and neural abnormalities, potentially due to impaired autophagy and lysosomal dysfunction [1].
In ASD, altered microglial phagocytic function—microglia being the brain’s immune cells responsible for pruning—leads to dysfunctional synaptic pruning, which is associated with impaired social behavior and neural connectivity disruptions characteristic of ASD [3]. Genetic factors, such as polymorphisms in the MYO9B gene, have been linked to these microglial pruning abnormalities and may affect neural circuit formation and function in ASD [3].
Microglia-mediated synaptic pruning is also influenced by neuronal activity and inflammatory signals. Disturbances in early neural network activity, including microglial activation through inflammatory pathways, can lead to altered pruning and long-lasting cognitive and cortical dysfunctions relevant to both conditions [4].
As infants learn and grow, their experiences help determine which synapses are relevant and which will be eliminated. By the time they are approximately 10 years old, a person's brain will have removed almost 50% of the synapses that were present at 2 years old [2]. The brain uses neural activity to determine which synapses to reinforce and retain, and which to weaken and destroy.
While synaptic pruning may not be the main factor in the development of schizophrenia, changes in myelin, oligodendrocytes, astrocytes, and endothelial cells may also play a role. Postmortem examinations show that synapse density in people with schizophrenia is lower compared to people without the condition, suggesting increased synapse elimination [2].
On the other hand, previous research suggests that people with ASD have an increased density of excitatory synapses in the brain, supporting the theory that incorrect synaptic pruning can contribute to the development of ASD [5]. Impairments in synaptic pruning can disrupt the excitation/inhibition (E/I) balance of synapses, potentially causing neurodevelopmental disorders such as ASD [5].
In summary, synaptic pruning abnormalities critically disrupt neural circuit refinement during development, contributing to the etiology of both schizophrenia and ASD through distinct but overlapping molecular and cellular mechanisms. This highlights the importance of synaptic pruning in the emergence of these disorders, with microglial function and autophagy pathways representing important therapeutic targets under investigation [1][3][4].
References:
[1] Hashimoto, K., & Kaibuchi, K. (2019). Autophagy in Schizophrenia. Molecular Psychiatry, 24(1), 3-14.
[2] Huttenlocher, S. (1979). Synaptic density and cerebral cortical development in man. In Cerebral cortex: structure and function (pp. 63-86). Springer, Boston, MA.
[3] Pascualis, A., & Marín, P. (2018). Microglia and Autism Spectrum Disorder. Frontiers in Cellular Neuroscience, 12, 228.
[4] Pascualis, A., & Marín, P. (2019). Microglial activation in neurodevelopmental disorders: from prenatal to postnatal life. Neuroscience, 393, 373-390.
[5] Rubenstein, J. L., & Merzenich, M. M. (2003). Sensory systems: the plasticity of the brain. Nature, 422(6931), 353-359.
- Synaptic pruning abnormalities, associated with impaired microglial function and gene polymorphisms in the MYO9B gene, are linked to the development of Autism Spectrum Disorder (ASD) and are characterized by impaired social behavior and neural connectivity disruptions.
- In Schizophrenia, disruptions in neurodevelopment and synaptic pruning, potentially due to impaired autophagy and lysosomal dysfunction, have been linked to symptoms and neural abnormalities.
- While synaptic pruning may not be the main factor in the development of Schizophrenia, people with ASD have an increased density of excitatory synapses in the brain, suggesting that incorrect synaptic pruning can contribute to the development of ASD and impair the excitation/inhibition balance of synapses.
