During neurodevelopment, the brain fabricates an incredible number of neurons which then migrate to specific parts of the brain. The development of new neurons is active all the way through infancy and childhood, continuing in a few select areas of the brain in adulthood to affect learning and memory, as well as mood regulation. However, just how this neurogenesis is switched on and off is still not understood.  Now, a study from researchers at the UNC School of Medicine identifies a brain circuit regulating the creation of neurons, running from near the front of the brain back to the hippocampus, a learning, and memory-related structure. The team states their data suggests the hippocampus is one of the major sites of neurogenesis in the adult human brain and the circuit identified is the regulator of this neuron-producing process.  The study is published in the journal Cell Stem Cell.

Previous studies show neurogenesis in the dentate gyrus (DG) occurs throughout adult life and supports crucial hippocampal functions, such as storing and retrieving memories. and regulating mood.  Previous studies from the lab showed special localized hippocampal neurons, known as parvalbumin (PV) interneurons, provide signals to newborn progeny in the DG linked to healthy neurogenesis.  The current study shows 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 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 in mice show the medial septum-to-hippocampus circuit works to keep DG stem cells in this normal, low-activity state. Data findings show the circuit acts as a brake on DG stem cell activation and helps to maintain a healthy DG stem cell population.

Results show interfering with this circuit takes off the brake completely, allowing DG stem cells to become overactive. Data findings show 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 stresses new neurons produced in this excessive burst of neurodevelopment appear unhealthy and conclude it’s likely the production of these abnormal neurons in the hippocampus could lead to learning and memory deficits.

The team surmises their study identifies the circuit controlling the activity of stem cells in the part of the hippocampus where neurogenesis occurs throughout adulthood.  For the future, the researchers are now studying the function of the newly discovered circuit using Alzheimer’s mouse models.

Source: UNC School of Medicine

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