Neuroscientists at Ludwig-Maximillians-University of Munich have made new revelations about the development of cerebellar granule neurons. The smallest and most numerous type of neuron in the human brain, these cells transmit motor and sensory information to Purkinje cells, large neurons that are said to play a role in coordinating motor movement and are the sole source of output for the cerebellar cortex.

Human cerebellum section with silver staining. Image from the Iowa Virtual Slidebox

The scientists found that humans generate most cerebellar granule cells after birth (85 percent), a finding that contradicts previous studies, which say the majority of these cells are generated prenatally.

Using Stereo Investigator, the researchers conducted a stereological study of the cerebella of 14 infants who died before their first birthday. They used Optical Fractionator probe to estimate the number of Purkinje and granule cells in cresyl violet stained sections of each brain. Performing a statistical analysis with the information they acquired, they determined that the number of granule cells per Purkinje cell in the human cerebellum increases with age during the first year of life. According to the paper, the population of granule cells grows from approximately 485 per Purkinje cell in the first month after birth to approximately 2,700 at month 11.

“The results of the present study indicate that damaging events during the first year of life may affect the cerebellum and, therefore, motor control, attention, emotions, mood and social behaviors much more severely than generally thought,” the authors say in their paper, adding that more new research should be carried out on postnatal neurogenesis in the human brain.

Kiessling, M., Büttner, A., Butti, C., Müller-Starck, J., Milz, S., Hof, P., Frank, H., Schmitz, C. (2013). Cerebellar granule cells are generated postnatally in humans. Brain Structure and Function, 1-16. doi: 10.1007/s00429-013-0565-z.

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Mice with the NHE6 gene mutation show less dendritic branching. Using Neurolucida, researchers traced a GFP-labeled neuron reconstructed with confocal z stacks in a wild type mouse (left) and a mouse with a mutant NHE6 gene (right). Image courtesy of first author Qing Ouyang, PhD, Alpert Medical School, Brown University.

Children with the neurogenetic disorder Christianson Syndrome experience delays in language and learning; they may also have seizures, and display symptoms of autism. Scientists say these disorders are a result of stunted brain cell growth, which occurs because of a mutation in the gene that produces the protein NHE6—a protein also mutant in several forms of autism.

Neurons in human brains with the mutant gene don’t branch as robustly or form connections as well as neurons in normal brains. But researchers at Brown University may have found a way to restore the ability of these cells to grow properly.

In their study, published in the journal Neuron, senior author Dr. Eric Morrow and his team describe a signaling pathway for neuronal growth involving NHE6. Using a mouse model with an NHE6 gene mutation, they found that reduced levels of NHE6 combined with increased acidity in a cell’s endosome, results in a depletion of the receptor protein TrkB, a key player in the growth and branching of axons and dendrites.

To instigate branching, TrkB binds with another protein, BDNF. Hypothesizing that increased levels of BDNF would enhance TrkB signaling and rescue branching, the scientists directly injected the protein into cells. Using Neurolucida to trace wild type and mutant neurons treated with BDNF, they found branching of axons and dendrites in mutant cells increased to a level “approaching wild type levels.”

Specifically, the paper reports an increase in axonal branching from 16.7 branch points per cell to 27.7; dendritic branching increased from 20.3 branches per cell to 34.4; and primary dendrites increased from an average of 6.5 to 8.7.

“In this paper we show that BDNF signaling is attenuated in the mutant mice, but it’s not blocked,” Dr. Morrow told Brown University in a press release. “You can rescue the [neuronal growth] by turning up the signaling.”

Ouyang, Q., Lizarraga, SB., Schmidt, M., Yang, U., Gong, J., Ellisor, D., Kauer, JA, Morrow, EM. (2013). Christianson Syndrome Protein NHE6 Modulates TrkB Endosomal Signaling Required for Neuronal Circuit Development. Neuron. 2013 Oct 2;80(1):97-112. doi: 10.1016/j.neuron.2013.07.043

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To a child with autism the world is an intense place. Strangers unnerve. Surprises unsettle. To cope, the autistic child creates his own internal world. It’s placid, secure, and void of extremes.

Though autism is one of the most common childhood developmental disorders in existence, affecting an estimated one in 110 children, we know little about how it works. Most theories suggest a deficiency in the brain caused by some combination of genetics and environmental factors. But Drs. Kamila and Henry Markram of the Ecole Polytechnique Fédérale in Lausanne say it’s not a deficient brain that makes autistic people socially inept, linguistically challenged, and prone to obsession. It’s actually the opposite. The brains of autistic people are so supercharged, they say, that their life experiences overwhelm them.

In their paper “The Intense World Theory — a unifying theory of the neurobiology of autism” (Frontiers in Neuroscience, 2010), the Markrams explain how overly strong reactions make the autistic brain excessively selective. This phenomenon, they say, becomes more extreme with each experience until the autistic eventually disassociates him or herself from “a painfully intense world.”

The Markrams studied the valproic acid rat, an animal model of autism. Their analysis of the rats’ neocortex and amygdala revealed hyper-reactivity and hyper-plasticity of the neural microcircuits in these areas of the brain — an unusual physiology that results in hyper-perception, hyper-attention, hyper-memory and hyper-emotionality.

“Basically, our theory really says that most autistic people or people with Asperger’s are savants,” Kamila Markram told New Scientist. “But this is buried under social withdrawal and fear of new environments. Their resistance to interaction and fear may obscure the hypercapability that they have. It may well turn out that successful treatments could expose truly capable and highly gifted individuals.”

Read “The Intense World Theory — a unifying theory of the neurobiology of autism” at Frontiers in Human Neuroscience.

April is Autism Awareness Month. Learn more about autism and find out how you can help at autism-society.org.

{Markram K and Markram H (2010) The Intense World Theory – a unifying theory of the neurobiology of autism. Front. Hum. Neurosci. 4:224. doi: 10.3389/fnhum.2010.00224}

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