| dc.description.abstract | The mammalian adult dentate gyrus generates new neurons. In a process called
adult neurogenesis neural stem cells give rise to new neurons that mature and
integrate into the existing neural network. By their addition and integration to the
existing network, the new neurons form new circuits. In their immature stages the
neurons are distinct in their morphology, physiology and protein expression from
mature neurons in the dentate gyrus. Several lines of evidence implicate the
immature neurons in learning and memory as well as other brain functions. Chapter
two of this thesis summarizes the involvement of new neurons in memory
formation during a critical period of their maturation. During this critical period the
newly formed neurons are thought to play a unique role in supporting hippocampal
function.
The proliferation of neural stem cells is the first step of circuit formation by new
neurons. This step of circuit formation by new neurons is regulated by several
factors. Amongst them is activity of surrounding neurons. However, not all cellular
players regulating proliferation in this fashion have been identified. To find out
which cell types play which roles in the regulation of proliferation, optogenetics is
suited. Optogenetics offers a method that can control specific cell types and
thereby investigate their individual role in adult neurogenesis. Chapter three and
four of this thesis focus on the practical aspects of implementing optogenetic
methods.
Chapter five of this thesis describes a study indicating a novel mechanism of
control, namely how activity of spatially modulated cells (place cells) and granule
cells may affect adult neurogenesis in the dentate gyrus. We found that place cell
activity anatomically correlates with doublecortin expressing cells while this
relationship was not present for interneurons. This supports the idea that place cell
activity locally increases neurogenesis. When we optogenetically induced activity
in granule cells, we found that proliferation increases significantly. Taken together,
the results from the in vivo recordings and optogenetic activation of granule cells,
we suggest that place cell activity induces proliferation of neuronal progenitor cells.
Activity dependent control of neurogenesis supports the notion that new neurons
are added when they are needed. The anticipated need is decided by activity, and
this may be a way to add the minimal amount of new neurons to still allow the
dentate gyrus to function with the best possible efficacy. Besides this, activity
dependent control may regulate specifically in which anatomical loci new neurons are added. Specific addition of new neurons supports the idea that new neurons
form specific new circuits, which are functionally relevant.
In my thesis work I have implemented a technique that can be used to activate
specific types of neurons and elucidate the involvement of granule cells in adult
neurogenesis. We went on to use this technique to show that granule cell activity
can induce increases in proliferation of progenitor cells in the dentate gyrus. This
leads to increased neurogenesis. We show a previously undescribed mechanism of
regulating adult neurogenesis. This new mechanism suggests new neurons are
added in specific anatomical loci, allowing the formation of circuits that are suited
to represent specific information. | nb_NO |
