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Science Square (Issue 98)
Mar 1, 2014

Sequence Integration in the Brain

Basal ganglia subcircuits distinctively encode the parsing and concatenation of action sequences.
Jin et al. Nature Neuroscience, Jan 2014.

When we learn to play a musical instrument - say the guitar - first, we have to learn notes, scales and chords; only then we will be able to play a song. The very same rule applies to our basic functions. For example, when we learn how to read, we first learn the alphabet and the rules of grammar, and then we start making sense of sentences. Neuroscientists have been intrigued by this process for many years and they have wanted to understand how our brains efficiently perform complex cognitive functions by connecting separate elements to produce a unique meaningful sequence. A recent study shed some light on this very important question. Scientists found that a specific area of the brain, the basal ganglia, can signal the integration of individual elements into a behavioral sequence. Scientists designed an experiment where they first trained mice to perform gradually faster sequences of lever presses. This behavioral test is very similar to a person learning to play a guitar solo at an increasingly faster pace. Then, they recorded the neural activity in the basal ganglia of mice performing the task and discovered that basal ganglia neurons treat a whole sequence of actions as a single behavior. This mechanism is called "chunking," which allows the brain to efficiently organize memories and actions by integrating individual sequences. It seems like the basal ganglia implement the "chunking." The basal ganglia are known to include two major pathways, the direct and the indirect. Scientists found that these two pathways show similar activities during the initiation of movement, but show differential activations during the execution of behavioral sequences. Interestingly, basal ganglia circuits are implicated in Parkinson's and Huntington's disorders, in which learning of sequences are compromised. Further studies will reveal a more mechanistic understanding of sequence integration in the brain and potential interventions to enhance it in neurological disorders.

Single Gene Separates Queen from Workers

Ubx promotes corbicular development in Apis mellifera
Medved V. et al. Biology Letters, Jan 2014

In a hive of honey bees, the queen and worker bees have very different jobs. A new study shows that a single gene called Ultrbithrox (Ubx) separates a queen from worker bees. The Ubx gene was previously known to control leg and hindquarter development in bees. Interestingly, researchers now identified three functions for Ubx specific to worker bees. First, Ubx promotes the development of a smooth spot on the hind legs where the "pollen baskets" are located. Second, Ubx directs the formation of eleven perfectly spaced bristles on the section of the leg called the "pollen comb." Third, Ubx mediates the formation of the "pollen press" which is a protrusion that helps pack and transport pollen back to the hive. Essentially, the Ubx gene promotes the development of three different physical structures on worker bees so that they can collect and transport pollen. Researchers confirmed these findings by silencing the Ubx gene genetically in worker bees and found that specialized leg features, including pollen combs and pollen presses, completely disappeared in the absence of the Ubx gene. Moreover, analyses of other bee species in the region revealed that the size and complexity of pollen baskets are directly correlated with the social behaviors of the particular bee species, suggesting that pollen baskets have yet-to-be-identified roles on the social behaviors of bees. Furthermore, the pollination of 35 percent of the world's crops (with a $216 billion market value) depends on bees carrying pollen from one flower to another. This study might help us to develop new genetic approaches to make bees better, more efficient pollinators and to ultimately combat the worldwide pollination problem.

Molecular Switch in Aging Blood Cells Discovered

A canonical to non-canonical Wnt signaling switch in haematopoietic stem-cell ageing
Florian MC et al. Nature, October2013

Every single cell in our body ages over time. The aging of a cell is typically characterized by the progressive loss of physiological function and increased vulnerability to death. The aging of our cells/tissues/organs is the primary risk factor for any human diseases. One critical cell type that dramatically changes its properties during aging are blood stem cells, aka Hematopoietic Stem Cells (HSCs). Young HSCs have the capacity to differentiate into the diverse lineages of erythroid, lymphoid, and myeloid cells. Young HSCs are polarized (asymmetrical) cells, in which distinct cytoskeletal proteins (also called the "polarity complex") are asymmetrically distributed within. However, the aged HSCs are mostly apolarized (symmetrical) cells and they differentiate only into lineages of myeloid cells (including, red blood cells, macrophages and monocytes) rather than lymphocytes (white blood cells in the immune system). The molecular changes in aging HSCs have largely been unknown. A recent study published in Nature shed some light onto the molecular identity of the ageing HSCs. Scientists showed that ageing HSCs have higher levels of a secreted protein called WNT5a, whereas the young HSCs have almost no WNT5a protein expressed in the cell. Moreover, the increased levels of WNT5a are found to attenuate the levels of the "polarity complex" proteins in HSCs and thus result in apolarized cells, which resemble the aging HSCs. Furthermore, transplantation studies revealed that increased WNT5a levels cause aging-related phenotypes and low Wnt5a levels promote a rejuvenation process in mice. These findings show that Wnt5a is the key molecule that controls the shift between young and old HSCs. Therapeutic approaches using antagonists of the Wnt5a molecule could potentially alleviate aging-related pathologies in the patients with a variety of blood diseases.