Study identifies how adult brain circuits regulate new neuron production.

During neurodevelopment the brain creates an incredible number of neurons, which migrate to specific parts of the brain. Contrary to popular belief, neurogenesis doesn’t stop at birth or even in childhood; in a few select areas of the brain, it can continue throughout adulthood, and is believed to be vitally important for certain forms of learning and memory, as well as in mood regulation. However, just how neurogenesis is switched on and off is still not understood.  Now, a study from researchers at the UNC School of Medicine identifies a neurogenesis-controlling brain circuit which runs from near the front of the brain back to the hippocampus, a learning- and memory-related structure. The team state that the hippocampus is one of the major sites of neurogenesis in the adult human brain, and the circuit that they have identified regulates this neuron-producing process.  The study is published in the journal Cell Stem Cell.

Previous studies show that neurogenesis in the dentate gyrus (DG) occurs throughout adult life and supports crucial hippocampal functions, such as storing and retrieving memories; DG neurogenesis has been linked to mood as well.  Previous studies from the lab showed that special local hippocampal neurons, called parvalbumin (PV) interneurons, provide signals to DG newborn progeny which appear to be crucial for healthy neurogenesis.  The current study shows that hippocampal PV interneuron-signaling is regulated by a GABA circuit originating from the medial septum, a cluster of neurons near the front of the brain.

The current study shows that the medial septum GABA circuit works through the local PV interneurons in the hippocampus to instruct stem cells to become activated or to stay quiet.  Results show in mice that the medial septum-to-hippocampus circuit works to keep DG stem cells in this normal, low-activity state. Data findings show that it acts like a brake on DG stem cell activation, and helps to maintain a healthy DG stem cell population.

Results show that interfering with this circuit takes off the brake completely, allowing DG stem cells to become overactive. Data findings show that this DG stem cell over-activation caused a burst of newly made neurons and a massive depletion of the resident DG stem cell population.  The group stress that the new neurons produced in this excessive burst of neurogenesis appear unhealthy, and conclude that it’s likely the production of these abnormal neurons in the hippocampus could lead to learning and memory deficits.

The team surmise that their study identifies the circuit which controls the activity of stem cells in the part of the hippocampus where neurogenesis occurs throughout adulthood.  They go on to add that their findings could have implications for understanding and treating many brain disorders arising from aberrant hippocampal neurogenesis, including epilepsy, schizophrenia, depression, and Alzheimer’s disease.  For the future, the researchers are now studying the function of the medial septum-to-hippocampus circuit in the context of Alzheimer’s mouse models.

Source: UNC School of Medicine



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