Spatial learning sculpts the dendritic arbor of adult-born hippocampal neurons

Dendrites are the extensions of neurons that receive incoming information. Neurons have primary dendrites that further split off into secondary and tertiary dendritic branches. On each of these branches are thousands of synaptic connections with axons of neurons carrying incoming information. The result is a dendritic tree that is capable of receiving and integrating a wide array of information within a single neuron. This is one of the neurobiological mechanisms by which different components of a memory are thought to be joined.

Neurons are not born with dendrites and spines – they are acquired during a developmental process that takes many weeks (see here & here). During early development, the pattern of formation of dendrites and spines are sculpted by experience, as might be expected if dendrites and spines are anatomical structures involved in processing and storing sensory information. While a body of work has emerged suggesting adult-born neurons are involved in memory and behavior, no one has yet investigated whether experience is capable of altering the dendritic development of these new neurons. This paper by Tronel et al. is therefore very important because it is the first to look at this phenomenon. They show a dramatic acceleration of dendritic development in response to learning, suggesting a potentially powerful role for new neurons in storing and processing information.

It has been 10+ years since Gould et al. and Kempermann et al. showed that learning and enriched environments can enhance the survival of new neurons. These findings are logical precursors to the current study since, if these new neurons have all the necessary components,  they suggest experience could add to the mnemonic functions of the hippocampus. But subsequent studies indicated that experience could also decrease the survival of new neurons. So perhaps structural changes to new neurons that are more relevant to learning might be worth investigating. For example, in many of my own experiments, I have failed to observe learning-induced changes in the number of new neurons but, if the number of dendrites or spines is increased, then there could still be an enhanced ability to process information. Or there could be the removal of some spines and the formation of others, suggesting a transformation in the type of information processed by new neurons. To get at these possibilities, Tronel et al. used doublecortin (DCX) staining and retroviral-GFP labeling to visualize the dendritic structure of newborn neurons in rats that had either remained in their cage (non-learners) or had learned a spatial memory task, the Morris water maze.

Since the authors had previously shown that water maze learning enhances the survival of 1-week-old cells, they first examined whether water maze learning would also alter the dendritic structure of this same population of neurons. Training rats for 6 days and examining new BrdU+/DCX+ neurons the following day (i.e. when new neurons were 14-days-old) they found that the dendritic length and the number of dendritic branches was doubled compared to rats that sat in their home cage.

More remarkable is the duration that the increased dendritic complexity persisted. To get at this question a GFP retrovirus was used to label new neurons born 1 week before learning, since DCX is eventually downregulated and cannot be used to examine dendritic morphology in neurons more than ~2 weeks old.  They found that even 3 months after learning, maze-trained rats had longer dendrites, more branch points, and more dendritic ends. The differences were not trivial either – maze-trained rats had ~70% increases for all of these measures. The number of spines (and therefore putative synapses) was also elevated, 3-fold, and the proportion of spines that showed a mature, mushroom-shaped morphology was 6-fold greater than naive, untrained rats. Since the dendritic morphology of developmentally-born hippocampal neurons can be altered by learning, physiological changes in hormones, and exercise, it is also worth noting that in this study learning did not affect the dendritic complexity of mature granule neurons (though spines were not analyzed in mature neurons and it is possible that learning caused retraction and formation of spines in mature neurons with no overall effect in spine numbers or morphology), suggesting adult-born neurons are particularly sensitive to learning-related activity.

They go on to show that these structural changes in adult-born neurons are even more pronounced when rats learn a more challenging version of the water maze task, where the spatial location of the escape platform moves on a daily basis. They also show these effects require NMDA receptors, which are required for many forms of hippocampal-dependent memory. These additional experiments are notable but it is the basic finding – the magnitude and duration of the structural changes – that is most interesting to me. Here are some of the reasons why:

• previous studies have suggested that adult-born neurons reach a plateau in their functional development by ~8+ weeks of age. These data suggest that new neurons still have a long way to go before they become fully mature.
• the 8w developmental plateau in earlier studies could be normal for animals that have not had any significant life experience (what does this mean when the majority of scientific studies of the brain use naive, deprived animals as models?)
• when experience accelerates the dendritic development of new neurons, are those neurons now less plastic and less likely to contribute to future behaviors? In trying to understand why some studies report behavior deficits after neurogenesis ablation whereas others do not, I’m imagining that 6 weeks of neurogenesis ablation could have major effects on behavior if older (>6w) adult-born neurons are less plastic, perhaps because experience (experimenter handling, group housing, previous learning) accelerated maturation in the way Tronel et al. report. In contrast, if animals have been deprived of learning experiences, 6 weeks of neurogenesis ablation might not have any effects on behavior, because older neurons are still relatively immature and able to compensate.
• depending on how you look at it, it is valid to wonder how a relatively small population of new neurons can be important for behavior. If you now consider the fact that 3-month-old cells still have significant amounts of untapped storage capacity, the cumulative numbers of new neurons generated over 3 months no longer seems so small and insignificant

Reference

Tronel S, Fabre A, Charrier V, Oliet SH, Gage FH, & Abrous DN (2010). Spatial learning sculpts the dendritic arbor of adult-born hippocampal neurons. Proceedings of the National Academy of Sciences of the United States of America, 107 (17), 7963-8 PMID: 20375283