TY - JOUR
T1 - Glia determine the course of brain-derived neurotrophic factor-mediated dendritogenesis and provide a soluble inhibitory cue to dendritic growth in the brainstem
AU - Martin, J. L.
AU - Brown, A. L.
AU - Balkowiec, A.
N1 - Funding Information:
The authors thank Dr. Anke Vermehren-Schmaedick for valuable discussions during the course of these studies, Drs. Michael C. Andresen, Gary A. Banker, Matthew Frerking, and Beth A. Habecker for invaluable input on experimental design, Dr. Stefanie Kaech for expert advice with imaging, and Dr. Michael J. Meredith for helpful advice on regression analysis. This work was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health (award number R01 HL076113 to A.B.). J.L.M. was supported in part by an individual pre-doctoral fellowship from the American Heart Association Pacific Mountain Affiliate (award number 10PRE2610114 ) and the Tartar Trust Foundation. The authors declare no conflict of interest.
PY - 2012/4/5
Y1 - 2012/4/5
N2 - Cardiorespiratory control neurons in the brainstem nucleus tractus solitarius (NTS) undergo dramatic expansion of dendritic arbors during the early postnatal period, when functional remodeling takes place within the NTS circuitry. However, the underlying molecular mechanisms of morphological maturation of NTS neurons are largely unknown. Our previous studies point to the neurotrophin brain-derived neurotrophic factor (BDNF), which is abundantly expressed by NTS-projecting primary sensory neurons, as a candidate mediator of NTS dendritogenesis. In the current study, we used neonatal rat NTS neurons in vitro to examine the role of BDNF in the dendritic development of neurochemically identified subpopulations of NTS neurons. In the presence of abundant glia, BDNF promoted NTS dendritic outgrowth and complexity, with the magnitude of the BDNF effect dependent on neuronal phenotype. Surprisingly, BDNF switched from promoting to inhibiting NTS dendritogenesis upon glia depletion. Moreover, glia depletion alone led to a significant increase in NTS dendritic outgrowth. Consistent with this result, astrocyte-conditioned medium (ACM), which promoted hippocampal dendritogenesis, inhibited dendritic growth of NTS neurons. The latter effect was abolished by heat-inactivation of ACM, pointing to a diffusible astrocyte-derived negative regulator of NTS dendritic growth. Together, these data demonstrate a role for BDNF in the postnatal development of NTS neurons, and reveal novel effects of glia on this process. Moreover, previously documented dramatic increases in NTS glial proliferation in victims of sudden infant death syndrome (SIDS) underscore the importance of our findings and the need to better understand the role of glia and their interactions with BDNF during NTS circuit maturation. Furthermore, while it has previously been demonstrated that the specific effects of BDNF on dendritic growth are context-dependent, the role of glia in this process is unknown. Thus, our data carry important implications for mechanisms of dendritogenesis likely beyond the NTS.
AB - Cardiorespiratory control neurons in the brainstem nucleus tractus solitarius (NTS) undergo dramatic expansion of dendritic arbors during the early postnatal period, when functional remodeling takes place within the NTS circuitry. However, the underlying molecular mechanisms of morphological maturation of NTS neurons are largely unknown. Our previous studies point to the neurotrophin brain-derived neurotrophic factor (BDNF), which is abundantly expressed by NTS-projecting primary sensory neurons, as a candidate mediator of NTS dendritogenesis. In the current study, we used neonatal rat NTS neurons in vitro to examine the role of BDNF in the dendritic development of neurochemically identified subpopulations of NTS neurons. In the presence of abundant glia, BDNF promoted NTS dendritic outgrowth and complexity, with the magnitude of the BDNF effect dependent on neuronal phenotype. Surprisingly, BDNF switched from promoting to inhibiting NTS dendritogenesis upon glia depletion. Moreover, glia depletion alone led to a significant increase in NTS dendritic outgrowth. Consistent with this result, astrocyte-conditioned medium (ACM), which promoted hippocampal dendritogenesis, inhibited dendritic growth of NTS neurons. The latter effect was abolished by heat-inactivation of ACM, pointing to a diffusible astrocyte-derived negative regulator of NTS dendritic growth. Together, these data demonstrate a role for BDNF in the postnatal development of NTS neurons, and reveal novel effects of glia on this process. Moreover, previously documented dramatic increases in NTS glial proliferation in victims of sudden infant death syndrome (SIDS) underscore the importance of our findings and the need to better understand the role of glia and their interactions with BDNF during NTS circuit maturation. Furthermore, while it has previously been demonstrated that the specific effects of BDNF on dendritic growth are context-dependent, the role of glia in this process is unknown. Thus, our data carry important implications for mechanisms of dendritogenesis likely beyond the NTS.
KW - Astrocyte
KW - GAD67
KW - GFAP
KW - Nucleus tractus solitarius
KW - TH
KW - VGlut2
UR - http://www.scopus.com/inward/record.url?scp=84862809377&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862809377&partnerID=8YFLogxK
U2 - 10.1016/j.neuroscience.2012.01.013
DO - 10.1016/j.neuroscience.2012.01.013
M3 - Article
C2 - 22306205
AN - SCOPUS:84862809377
SN - 0306-4522
VL - 207
SP - 333
EP - 346
JO - Neuroscience
JF - Neuroscience
ER -