[Published 16th November 2010 02:30 PM GMT]

Novel touch stimuli can stimulate neurogenesis in the spinal cord of mice, according to a study published online today (16 November) in Molecular Psychiatry, suggesting that neurogenesis may be an important component of touch sensation.

Image: Wikimedia commons, Aaron Logan

"This is a very interesting and unexpected result," said neuroscientist Pierre-Marie Lledo of the Institut Pasteur in France, who was not involved in the research. Neurogenesis in the spinal cord has predominately only been documented in vitro, he said. "To see indeed you have neurogenesis in vivo in the dorsal horn of the spinal cord is rather puzzling and very interesting," and suggests a new mechanism by which organisms may be able to process complex tactile environments, Lledo noted. 


Recently, however, neuroimmunologist Michal Schwartz of The Weizmann Institute of Science and her colleagues discovered proliferating neural progenitor cells in the dorsal horn of the mouse spinal cord. Because this part of the spinal cord is known to be composed of predominately sensory neurons, "it gave us an idea that [these new neurons] are participating in pain and/or touch sensation," Schwartz said. 

To test this idea, the team placed mice in enriched cages containing sandpaper, gravel, or sponge substrates, or a combination, for 2 hours and measured new cell production in the spinal cord. Just 2 hours after exposure to the enriched environments, the mice showed a dramatic increase in the number of new cells in the dorsal horn. The amount of neurogenesis was greater in mice exposed to environments with a combination of substrate types, suggesting that cell proliferation may be a response not only to the novelty of an environment, but to its diversity as well. 

"We had not expected to have such an amazing effect," said Ravid Shechter, a graduate student in Schwartz's lab who helped execute the experiments. "It was a very fast response to the environment." 

"It was a huge surprise," agreed neuroimmunologist and coauthor Asya Rolls, a prior member of the Schwartz lab and a current postdoc at Stanford University. "[Neurogenesis is] an additional component that was never even suggested in this field [of touch sensation]." 

To test the role of neurogenesis in habituation to stimuli, the team exposed the mice to the environments repeatedly over a 7-day period, or permanently housed them in the enriched cages. In contrast to the single exposure experiments, repeated exposures did not result in increased neurogenesis, and continuous exposure even seemed to inhibit the process. Further analysis of the cells revealed that instead of proliferating, the newly formed cells had begun to differentiate, mostly into GABAergic immature neurons. As inhibitory neurons, these GABAergic cells may play a role in habituation. 

The immature neurons tended to die within just four weeks, however, Lledo noted. What drives neuronal death is unclear, but even at a young age, these neurons can be active. "The same category of neurons the same age in the olfactory bulb, we have been able to demonstrate about one week after birth these newborn neurons indeed release GABA." Thus, even though the neurons fail to mature, they may still have functional consequences, he said. 

Indeed, the findings show a striking similarity to the process of adult neurogenesis in the olfactory bulb, said Lledo, where exposure to different odors has been found to stimulate cell proliferation. "If you look at the brain of a mouse living in a very clean and boring cage, the number of neurons is quite reduced," he said. "But as soon as you change the odorants every day, you stimulate the neurons two or three [fold]." Thus, the process of neurogenesis and differentiation may be "a more general phenomenon of plasticity in the sensory organs," he said. 

The finding that neurogenesis may be an integral component of touch sensation may have implications for pain management and the treatment of pain diseases, Lledo added. Because these new GABAergic neurons, which are known to be inhibitory, are generated where pain fibers terminate in the spinal cord, "more newborn neurons located here will provide more inhibition to these nocioceptive fibers, and therefore will change the threshold of pain." 

Furthermore, the results may provide some answers with regard to touch treatments used in alternative medicine, Schwartz said, for which the mechanisms are currently a bit of a mystery. "In this regard, [our results] may give a scientific basis to unexplained effects of touch treatment." 

R. Shechter, et al., "Touch gives new life: mechanosensation modulates spinal cord adult neurogenesis," Molecular Psychiatry, 1-11, 2010. 

While researchers agree that the birth of new neurons plays an important role in the adult brain, they have long debated to which aspects of learning, memory and behavior the process contributes. A new study published today (January 30) in Nature has used a gene knockout approach to link adult neurogenesis to spatial learning. 

The paper showed that adult mice that were deficient for a neurogenesis-linked gene , Tlx, had diminished learning and memory capabilities compared to their wild-type counterparts. The researchers, led by Ronald Evans at the Salk Intsitute for Biological Studies, demonstrated that knock-out mice took, in some cases, 10% longer than the controls to navigate a water maze. 

In the past, researchers have irradiated the hippocampus or used drugs that blocked neurogenesis to observe the outcome on behavior in animal models. But using a genetic approach adds a lot of power to the study, Elizabeth Gould of Princeton University, who was not involved in the study, told The Scientist; those other methods may have in fact prompted neurogenesis to compensate for the impairment, Gould added. 

But Martin Wojtowicz's group at the University of Toronto has shown conflicting results . His studies suggest that neurogenesis does not play a role in spatial learning, but instead strongly affected contextual fear conditioning (a learned fear response to a place). "It's puzzling why they got the opposite results," Wojtowicz told The Scientist, but added that differences in methodology -- Wojtowicz used irradiation, not genetics -- and the choice of which gene to knock out could all yield varying results. While the current paper used mice, the Wojtowicz group's work used rats, which may account for differences in the water maze test, but not the fear conditioning test; rats are better swimmers than mice, but both rats and mice easily learn to be afraid of a specific place. 

"The problem is different methods are being used, many different time points are being examined, different learning paradigms used, and the results are not consistent across studies," said Gould. There is no debate that neurogenesis does play some role in the adult brain, she said, but exactly what that role is remains to be seen.

 

[Published 15th February 2007 05:05 PM GMT]

Neurogenesis indeed occurs in the human adult brain, according to a new paper in this week's Science. The findings provide new evidence for the long-controversial theory, and suggest that neurogenesis occurs in the olfactory bulb and follows the same pattern as in other mammalian brains. 

The new paper "disproves the dogma that the human brain doesn't have similar pathways of neurogenesis to that found in other mammalian brains," author Richard L.M. Faull of the University of Auckland said in an Email. 

"The data are very nice and very clear, just what we'd expect based on rodent work," agreed Heather Cameron, of the National Institute of Mental Health in Bethesda, MD, who is not connected to the study. 

Many vertebrates create new central nervous system neurons at all stages of life. This talent is linked to the ability to regenerate after CNS injury, so is most common in fish and amphibians. For most of the 20th century, conventional wisdom held that neurogenesis in mammals happened exclusively during embryonic and early postnatal life. Only within the last decade have researchers come to accept that adult neurogenesis does occur in selected mammalian brain regions, notably the hippocampus and olfactory system. However, neurogenesis in the human adult olfactory bulb has remained controversial. 

Faull and his colleagues found that baby neurons called neuroblasts, born in the subventricular zone (SVZ), reach the human adult olfactory bulb, and do it via the rostral migratory stream (RMS). Rodents use an RMS too, although it differs anatomically from the human RMS. Using MRI, cell-specific markers, and electron microscopy, the researchers found progenitor cells with migratory characteristics, and also cells that become mature neurons in the olfactory bulb, in the adult human RMS. 

However, Arturo Alvarez-Buylla at the University of California-San Francisco said he is not convinced by the findings. "It is an interesting work, but it does not demonstrate neurogenesis and much less migration along the RMS," he said in an Email." Indeed, the findings appear to contradict a 2004 Naturepaper he co-authored, which found no migrating neuroblasts in the human SVZ or in the pathway to the olfactory bulb. 

Fred Gage, of the Salk Institute for Biological Studies in La Jolla, CA, who was not connected with the study, said he expected the new paper to cite 2004 work by Andr￩anne Bedard and Andr￩ Parent, which also offered evidence of newly generated neurons in the human olfactory bulb. (Indeed, Princeton'sElizabeth Gould said in an Email she was "pleased to see these authors have corroborated and extended the work of Bedard and Parent.") The newest paper uses more technology, focuses more on the RMS, and in general provides more evidence, but "they do come to a very similar conclusion," Gage said in an Email. 

Parent himself said he admired the latest findings, but was "disappointed" the authors did not mention his work. "We have the very highest respect for Dr Parent's work and we very much apologize for this oversight," Faull responded. 

Questions remain, however, as to what those new neurons can actually do, given that the function of neurogenesis remains somewhat of a mystery. Seizures stimulate neuron increase in the hippocampus, "but we don't know whether [neurogenesis] is trying to compensate" for damaged neurons, Cameron told The Scientist. There's some evidence new neurons may combat depression, she noted, but increasing neuron number would not necessarily be helpful in all conditions. 

According to Faull, he and his colleagues have preliminary unpublished evidence that SVZ neural precursors don't just move to the olfactory bulb, but also leave the RMS and head for adjacent regions of the basal ganglia and cerebral cortex. In experimental rat models of diseases like Parkinson's, migratory neuroblasts replace neurons lost in the basal ganglia, suggesting this neural migration could have therapeutic benefits, he said.