Genomes and Genes
Novel signaling between striatal neurons and postnatal neural progenitors
Principal Investigator: Stephanie Young
Abstract: DESCRIPTION (provided by applicant): Neurogenesis in the subventricular zone (SVZ) of mammals is known to occur post-natally and continues into late adulthood. The SVZ is made up of GFAP-positive stem cells and neuronal precursors that migrate from the SVZ to the olfactory bulb to become interneurons. In order to understand how these cells proliferate, migrate, and differentiate, it is necessary to elucidate cell-cell signaling in the SVZ, as well as examine the influence of mature networks on the SVZ. Mature neurons are known to surround the SVZ. Despite the proximity of neurons in the striatum to the SVZ, research indicating contact and functional communication behween striatal neurons and progenitors residing in the SVZ is lacking. The majority of neurons in the striatum are GABA-ergic and are a potential source of signals regulating SVZ cells. GABA has been shown to mediate proliferation and migration (Nguyen et al., 2003, Wang et al., 2003, Bolteus &Bordey, 2004). The main objective of this proposal is to look at the interaction between striatal neurons and SVZ cells using dye-filling, calcium imaging, and patch clamp techniques. Aim 1 proposes to determine the presence of striatal neuron processes in the SVZ and characterize neuronal subtype using morphology and electrophysiology. My preliminary data show GABA-ergic spiny neurons from the striatum have processes projecting into the SVZ. Aim 2 proposes to examine functional signaling between striatal neurons and SVZ neuroblasts and astrocytes using calcium imaging and electrophysiology on SVZ cells while stimulating striatal neurons. Stimulation of striatal neurons should increase calcium transients as well as increase GABA-ergic conductance as detected by patch clamp. The proposed research will investigate one potential mechanism by which striatal networks can signal to SVZ stem cells and neuroblasts. Medial temporal lobe epilepsy (MTLE) with tonic-clonic seizures is thought to begin in the piriform or olfactory cortex, and seizures have been shown to increase neurogenesis in the SVZ (Parent et al., 2002). In addition, GABA-ergic striatal networks can not only be affected by epilepsy, but also by anti-epileptic treatments that increase GABA- ergic tone (Calabresi, 1999, Fink et al., 2000). However, the mechanism for increased neurogenesis due to seizure is still unknown. Relevance: This proposal and its findings will demonstrate how neurons signaling to progenitor cells may contribute to postanatal neurogenesis under physiological conditions, and implicate a pathway by which neurogenesis can be altered in a diseased brain through electrical connectivity. This novel pathway may be useful in modulating neurogenesis in the treatment of epilepsy and other neurological disorders.
Funding Period: ----------------2009 - ---------------2011-
more information: NIH RePORT
- NKCC1 knockdown decreases neuron production through GABA(A)-regulated neural progenitor proliferation and delays dendrite developmentStephanie Z Young
Department of Neurosurgery, Yale University, New Haven, Connecticut 06520 8082, USA
J Neurosci 32:13630-8. 2012..Thus, dysregulation in GABA(A) depolarizing activity delayed dendritic development and reduced NPC proliferation resulting in decreased neuronal density...
- GABA's control of stem and cancer cell proliferation in adult neural and peripheral nichesStephanie Z Young
Department of Neurosurgery, Yale University, New Haven, Connecticut, USA
Physiology (Bethesda) 24:171-85. 2009..Here, we will discuss GABA's presence as a near-universal signal that may be altered in tumor cells resulting in modified mitotic activity...
- Neurotransmitters couple brain activity to subventricular zone neurogenesisStephanie Z Young
Department of Neurosurgery, Yale University School of Medicine, 333 Cedar Street, FMB 422, New Haven, CT 06520 8082, USA
Eur J Neurosci 33:1123-32. 2011....