Proper brain function relies on the establishment and maintenance of complex neuronal circuits. Developmental genetic programs largely determine the brain's initial wiring diagram, but synaptic input ultimately sculpts its final form, function, and plasticity. Amazingly, the adult mammalian brain has evolved the ability to maintain and modify certain neural circuits through ongoing neurogenesis. This neurogenic potential is primarily restricted to the hippocampus and olfactory bulb, and is influenced by environmental enrichment, sensory stimulation, and even neurological disease. Although the sites and timing of adult neurogenesis have been well characterized, many ofthe cellular and molecular mechanisms that govern synapse and circuit formation in response to neural activity remain unknown. One hurdle that has limited our knowledge of this process has been the lack of precise control over neuronal activities. To address this we have initiated a series of cell biological, electrophysiological, and genetic experiments directed towards manipulating the activity of neuronal subsets in the olfactory bulb while investigating the cell-specific effects on synapse and circuit formation. Using natural odor stimulation and a mouse model that expresses the lightgated ion channel Channelrhodopsin-2 in subsets of neurons in the brain, we have found that mitral cell activation promotes newborn granule cell synaptogenesis and adult-born neuron survival. To better understand the cellular mechanisms of activity-dependent newborn neuron circuit integration, we have also begun to investigate the roles of NMDA receptor signaling. Preliminary data show that NMDA receptor function is important for proper dendrite and spine morphogenesis, synaptic function, and neuronal survival. The broad goal of the proposed research is to better understand how synaptic input intersects with developmental genetic programs to guide synapse formation and cell survival.

Public Health Relevance

Many neurological diseases, disorders, or traumas result in the selective loss of neuronal subsets. Investigating the natural phenomenon of neurogenesis in the adult mammalian brain presents a unique opportunity to better understand how synaptic activity and developmental genetics merge to drive functional circuit formation. Mechanistic knowledge gained on this dynamic relationship may prove useful towards neural stem cell based therapies.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Transition Award (R00)
Project #
Application #
Study Section
Special Emphasis Panel (NSS)
Program Officer
Owens, David F
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Baylor College of Medicine
Schools of Medicine
United States
Zip Code
Herman, Alexander M; Huang, Longwen; Murphey, Dona K et al. (2014) Cell type-specific and time-dependent light exposure contribute to silencing in neurons expressing Channelrhodopsin-2. Elife 3:e01481
Huang, Longwen; Garcia, Isabella; Jen, Hsin-I et al. (2013) Reciprocal connectivity between mitral cells and external plexiform layer interneurons in the mouse olfactory bulb. Front Neural Circuits 7:32
Garcia, Isabella; Kim, Cynthia; Arenkiel, Benjamin R (2013) Revealing neuronal circuitry using stem cell-derived neurons. Curr Protoc Stem Cell Biol Chapter 2:Unit 2D.15
Chen, Qian; Cichon, Joseph; Wang, Wenting et al. (2012) Imaging neural activity using Thy1-GCaMP transgenic mice. Neuron 76:297-308
Ung, Kevin; Arenkiel, Benjamin R (2012) Fiber-optic implantation for chronic optogenetic stimulation of brain tissue. J Vis Exp :e50004
Garcia, Isabella; Huang, Longwen; Ung, Kevin et al. (2012) Tracing synaptic connectivity onto embryonic stem cell-derived neurons. Stem Cells 30:2140-51
Wulff, Peer; Arenkiel, Benjamin R (2012) Chemical genetics: receptor-ligand pairs for rapid manipulation of neuronal activity. Curr Opin Neurobiol 22:54-60
G├╝ler, Ali D; Rainwater, Aundrea; Parker, Jones G et al. (2012) Transient activation of specific neurons in mice by selective expression of the capsaicin receptor. Nat Commun 3:746
Selever, Jennifer; Kong, Jian-Qiang; Arenkiel, Benjamin R (2011) A rapid approach to high-resolution fluorescence imaging in semi-thick brain slices. J Vis Exp :
Arenkiel, Benjamin R (2011) Genetic approaches to reveal the connectivity of adult-born neurons. Front Neurosci 5:48

Showing the most recent 10 out of 11 publications