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The Olfactory System is a useful place to study neural development:

    A) All Regions are highly organized and laminated, making subtle developmental changes easy to observe and quantify:

        
        B)  It never stops developing—both new sensory receptor neurons and central neurons are constantly added throughout life. As a result, all of the processes that characterize development: cell proliferation and differentiation, synaptogenesis and cell death occur throughout life

    C) The system has a very well studied wiring diagram; indeed since the time of Cajal we have had a good understanding of the general organization of the constiutent structures.  Interestingly, the organization seems to be very similar in animals as diverse as insects and people.

Olfactory bulb circuit
        D) It has an amazing wealth of neurotransmitters and neurochemical phenotypes


If you block airflow through one side of the nasal cavity (by closing the external nares (nostril), there is an immediate reduction in the activity of the principal neurons in the first central processing area of the olfactory system, the olfactory bulb.

Mitral cell activity in respiratory cycle

      (Philpot, Foster and Brunjes, J. Neurobiol. 33, 374 1997)

If you close a naris on the day after the day of birth in a rat (P1), and rear the animal until P30, the olfactory bulb on that side is 25 % smaller than that of a normal bulb.

Nissl section through olfactory bulbs

    (Brunjes, Brain Res. Reviews, 19, 146-160, 1994)

We know that the two bulbs are the same size on P1, but that decreased activity results in a huge difference by P30. How does this difference in the amount of input alter the pattern of development? Another way of saying this is to ask “Exactly how is it that ‘experience’ comes to affect the ways our brain grows?”

With over 2 decades of research we now know quite a bit about how growth differs in “experimental” vs normal control bulbs.

1)  Experimental bulbs are smaller because they contain fewer cells due to increased cell death. The death occurs primarily in interneuron populations (granule and periglomerular cells), the last added relay neurons (external tufted cells) and glia.

Tunel staining in olfactory bulb

        (e.g., Fiske and Brunjes, J. Comp. Neurol. 431, 311, 2001)

2) The decrease is not due to changes in the addition of new neurons (through the rostral migratory stream)

Rostral Migratry Stream P2 Rat

                 (Frazier-Cierpial and Brunjes, J. Comp. Neurol 289, 481, 1989.)

3) At least for one population (granule cells), the decrease is not due to changes in the size of cells.

Granule cell morphology by age

   (Frazier-Cierpial and Brunjes,. Developmental Brain Research 47, 129-136, 1989)

Not only can we cause the bulb to shrink in size by reducing input, we can cause it to return to normal size by reinstating normal activity. To our knowledge the olfactory bulb is the only area of the mammalian brain which can undergo a 25% reduction in size and then be rehabilitated back to normal solely though regulating its input.

Recovery is due to two things:

1) Increased cell survival in cells newly added to the bulb through the rostral migratory stream.  

brdu staining in olfactory bulb

  There are more BRDU labelled cells in the unplugged side (bottom, above)  than in a control bulb. (see Cummings, Henning and Brunjes, J. Neurosci. 17, 7433, 1997. )

2) Decreased cell death (Fiske and Brunjes, J. Comp. Neurol. 431, 311, 2001

brdu/calretinin double immunostaining


In sum, this line of research is designed to use the attractive properties of the olfactory bulb to ask some fundamental questions about how the brain development, including how function acts to modify how brains develop.

Relevant publications:

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