Dentate gyrus

The dentate gyrus is part of the hippocampal formation. It is thought to contribute to new memories as well as other functional roles. It is notable as being one of a select few brain structures currently known to have high rates of neurogenesis in adult rats, (other sites include the olfactory bulb and cerebellum).

Structure
The dentate gyrus consists of three layers of neurons: molecular, granular, and polymorphic. The middle layer is most prominent and contains granule cells that project to the CA3 subfield of the hippocampus. These granule cells project mostly to interneurons, but also to pyramidal cells and are the principal excitatory neurons of the dentate gyrus. The major input to the dentate gyrus (the so-called perforant pathway) is from layer 2 of the entorhinal cortex, and the dentate gyrus receives no direct inputs from other cortical structures. The perforant pathway is divided into the medial perforant path and the lateral perforant path, generated, respectively, at the medial and lateral portions of the entorhinal cortex. The medial perforant path synapses onto the proximal dendritic area of the granule cells, whereas the lateral perforant path does so onto the distal dendrites of these same cells.

Development
The granule cells in the dentate gyrus are distinguished by their late time of formation during brain development. In rats, approximately 85% of the granule cells are generated after birth. In humans, it is estimated that granule cells begin to be generated during gestation weeks 10.5 to 11, and continue being generated during the second and third trimesters, after birth and all the way into adulthood. The germinal sources of granule cells and their migration pathways have been studied during rat brain development. The oldest granule cells are generated in a specific region of the hippocampal neuroepithelium and migrate into the primordial dentate gyrus around embryonic days (E) 17/18, and then settle as the outermost cells in the forming granular layer. Next, dentate precursor cells move out of this same area of the hippocampal neuroepithelium and, retaining their mitotic capacity, invade the hilus (core) of the forming dentate gyrus. This dispersed germinal matrix is the source of granule cells from that point on. The newly generated granule cells accumulate under the older cells that began to settle in the granular layer. As more granule cells are produced, the layer thickens and the cells are stacked up according to age - the oldest being the most superficial and the youngest being deeper. The granule cell precursors remain in a subgranular zone that becomes progressively thinner as the dentate gyrus grows, but these precursor cells are retained in adult rats. These sparsely scattered cells constantly generate granule cell neurons, which add to the total population. Thus, granule cells in the dentate gyrus are possibly the only known population of neurons in the brain that are constantly increasing their numbers. In 2010, it was shown that the balance between neural stem cells (NSCs) and neural progenitor cells (NPCs) is maintained by an interaction between the epidermal growth factor receptor signaling pathway and Notch signaling pathway.

Function


The dentate gyrus is thought to contribute to the formation of memories and to play a role in depression.

Memory
The dentate gyrus is one of the few regions of the adult brain where neurogenesis (i.e., the birth of new neurons) takes place. Neurogenesis is thought to play a role in the formation of new memories. New memories could preferentially utilize newly-formed dentate gyrus cell, providing a potential mechanism for distinguishing multiple instances of similar events or multiple visits to the same location. A Study at the Human Nutrition Research Center on Aging showed that feeding blueberry extract to older rats for a short time frame increases neurogenesis in the dentate gyrus. This increased neurogenesis is associated with improved spatial memory, as seen through performance in a maze.

Stress and Depression
The dentate gyrus may also have a functional role in stress and depression. For instance, neurogenesis has been found to increase in response to chronic treatment with antidepressants. On the contrary, however, the physiological effects of stress, often characterized by release of glucocorticoids such as cortisol, as well as activation of the sympathetic division of the autonomic nervous system, have been shown to inhibit the process of neurogenesis in primates. Both endogenous and exogenous glucocorticoids are known to cause psychosis and depression, implying that neurogenesis in the dentate gyrus may play an important role in modulating symptoms of stress and depression.

Other
Some evidence suggests that neurogenesis in the dentate gyrus increases in response to aerobic exercise.

Blood Sugar
Studies by researchers at Columbia University Medical Center indicate that poor glucose control can lead to deleterious effects on the dentate gyrus.