Continued neurogenesis represents a remarkable means of cellular and structural neural plasticity in adult brain tissue, and elucidating the fundamental mechanisms that support and guide this phenomenon holds promise towards developing future approaches towards repairing damaged or diseased nervous tissue. Data have shown that numerous extrinsic physiological and pathological processes directly influence adult neurogenesis and synaptic integration of newborn neurons. Notably, increased neural activity enhances adult neurogenesis, synaptogenesis, and circuit remodeling, whereas decreased or altered neural activity compromises newborn neuron survival and integration. To date however, the identities of inputs that convey activity-dependent changes to newborn neurons, and the nature of their signaling in response to activity manipulations are only now beginning to be revealed. In the previous granting period of this award, we have identified previously unknown sources of input, and revealed novel neuromodulatory signaling mechanisms that contribute towards the activity- dependent wiring of newborn neurons in the adult brain. Here we will expand upon these findings to better understand the cellular mechanisms that promote the formation and stabilization of new synapses in adult brain tissue, and further assay how manipulating these pathways affects the formation and/or remodeling of new brain circuits.
We have recently uncovered that cholinergic neurons from the basal forebrain provide GABAergic input to adult-born neurons as they form new connections in adult brain tissue. Interestingly, signaling from the basal forebrain has been implicated in learning, reward, and reinforcement, all of which are physiological states that influence the survival and synaptic integration of adult-born neurons within neural circuits. Using a combination of conditional genetic, optogenetic, in vivo imaging, electrophysiology, and transcriptional profiling approaches, we will set out to determine the role for the cholinergic basal forebrain towards rewiring adult brain tissue.
|McClard, Cynthia K; Arenkiel, Benjamin R (2018) Neuropeptide Signaling Networks and Brain Circuit Plasticity. J Exp Neurosci 12:1179069518779207|
|Liu, Gary; Patel, Jay M; Tepe, Burak et al. (2018) An Objective and Reproducible Test of Olfactory Learning and Discrimination in Mice. J Vis Exp :|
|McClard, Cynthia K; Kochukov, Mikhail Y; Herman, Isabella et al. (2018) POU6f1 Mediates Neuropeptide-Dependent Plasticity in the Adult Brain. J Neurosci 38:1443-1461|
|Quast, Kathleen B; Ung, Kevin; Froudarakis, Emmanouil et al. (2017) Developmental broadening of inhibitory sensory maps. Nat Neurosci 20:189-199|
|Hanson, Elizabeth; Swanson, Jessica; Arenkiel, Benjamin R (2017) Sensory experience shapes the integration of adult-born neurons into the olfactory bulb. J Nat Sci 3:|
|Liu, Gary; McClard, Cynthia K; Tepe, Burak et al. (2017) Olfactory Cued Learning Paradigm. Bio Protoc 7:|
|Garcia, Isabella; Bhullar, Paramjit K; Tepe, Burak et al. (2016) Local corticotropin releasing hormone (CRH) signals to its receptor CRHR1 during postnatal development of the mouse olfactory bulb. Brain Struct Funct 221:1-20|
|Herman, Alexander M; Ortiz-Guzman, Joshua; Kochukov, Mikhail et al. (2016) A cholinergic basal forebrain feeding circuit modulates appetite suppression. Nature 538:253-256|
|Huang, Longwen; Ung, Kevin; Garcia, Isabella et al. (2016) Task Learning Promotes Plasticity of Interneuron Connectivity Maps in the Olfactory Bulb. J Neurosci 36:8856-71|
|Justice, Nicholas J; Huang, Longwen; Tian, Jin-Bin et al. (2015) Posttraumatic stress disorder-like induction elevates ?-amyloid levels, which directly activates corticotropin-releasing factor neurons to exacerbate stress responses. J Neurosci 35:2612-23|
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