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Corticotropin-releasing factor in the mouse central nucleus of the amygdala: ultrastructural distribution in NMDA-NR1 receptor subunit expressing neurons as well as projection neurons to the bed nucleus of the stria terminalis.
Exp Neurol 2013; 239:120-32EN

Abstract

Corticotropin-releasing factor (CRF) and glutamate are critical signaling molecules in the central nucleus of the amygdala (CeA). Central amygdala CRF, acting via the CRF type 1 receptor (CRF-R1), plays an integral role in stress responses and emotional learning, processes that are generally known to involve functional NMDA-type glutamate receptors. There is also evidence that CRF expressing CeA projection neurons to the bed nucleus of the stria terminalis (BNST) play an important role in stress related behaviors. Despite the potentially significant interactions between CRF and NMDA receptors in the CeA, the synaptic organization of these systems is largely unknown. Using dual labeling high resolution immunocytochemical electron microscopy, it was found that individual somata and dendrites displayed immunoreactivity for CRF and the NMDA-NR1 (NR1) subunit in the mouse CeA. In addition, CRF-containing axon terminals contacted postsynaptic targets in the CeA, some of which also expressed NR1. Neuronal profiles expressing the CRF type 1 receptor (CRF-R1), identified by the expression of green fluorescent protein (GFP) in bacterial artificial chromosome (BAC) transgenic mice, also contained NR1, and GFP immunoreactive terminals formed synapses with NR1 containing dendrites. Although CRF and GFP were only occasionally co-expressed in individual somata and dendritic profiles, contacts between labeled axon terminals and dendrites were frequently observed. A combination of tract tracing and immunocytochemistry revealed that a population of CeA CRF neurons projected to the BNST. It was also found that CRF, or GFP expressing terminals directly contacted CeA-BNST projection neurons. These results indicate that the NMDA receptor is positioned for the postsynaptic regulation of CRF expressing CeA neurons and the modulation of signals conveyed by CRF inputs. Interactions between CRF and NMDA receptor mediated signaling in CeA neurons, including those projecting to the BNST, may provide the synaptic basis for integrating the experience of stress and relevant environmental stimuli with behaviors that may be of particular relevance to stress-related learning and the emergence of psychiatric disorders, including drug addiction.

Authors+Show Affiliations

Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, NY 10065, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

23063907

Citation

Beckerman, Marc A., et al. "Corticotropin-releasing Factor in the Mouse Central Nucleus of the Amygdala: Ultrastructural Distribution in NMDA-NR1 Receptor Subunit Expressing Neurons as Well as Projection Neurons to the Bed Nucleus of the Stria Terminalis." Experimental Neurology, vol. 239, 2013, pp. 120-32.
Beckerman MA, Van Kempen TA, Justice NJ, et al. Corticotropin-releasing factor in the mouse central nucleus of the amygdala: ultrastructural distribution in NMDA-NR1 receptor subunit expressing neurons as well as projection neurons to the bed nucleus of the stria terminalis. Exp Neurol. 2013;239:120-32.
Beckerman, M. A., Van Kempen, T. A., Justice, N. J., Milner, T. A., & Glass, M. J. (2013). Corticotropin-releasing factor in the mouse central nucleus of the amygdala: ultrastructural distribution in NMDA-NR1 receptor subunit expressing neurons as well as projection neurons to the bed nucleus of the stria terminalis. Experimental Neurology, 239, pp. 120-32. doi:10.1016/j.expneurol.2012.10.009.
Beckerman MA, et al. Corticotropin-releasing Factor in the Mouse Central Nucleus of the Amygdala: Ultrastructural Distribution in NMDA-NR1 Receptor Subunit Expressing Neurons as Well as Projection Neurons to the Bed Nucleus of the Stria Terminalis. Exp Neurol. 2013;239:120-32. PubMed PMID: 23063907.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Corticotropin-releasing factor in the mouse central nucleus of the amygdala: ultrastructural distribution in NMDA-NR1 receptor subunit expressing neurons as well as projection neurons to the bed nucleus of the stria terminalis. AU - Beckerman,Marc A, AU - Van Kempen,Tracey A, AU - Justice,Nicholas J, AU - Milner,Teresa A, AU - Glass,Michael J, Y1 - 2012/10/12/ PY - 2012/07/20/received PY - 2012/09/21/revised PY - 2012/10/05/accepted PY - 2012/10/16/entrez PY - 2012/10/16/pubmed PY - 2013/3/1/medline SP - 120 EP - 32 JF - Experimental neurology JO - Exp. Neurol. VL - 239 N2 - Corticotropin-releasing factor (CRF) and glutamate are critical signaling molecules in the central nucleus of the amygdala (CeA). Central amygdala CRF, acting via the CRF type 1 receptor (CRF-R1), plays an integral role in stress responses and emotional learning, processes that are generally known to involve functional NMDA-type glutamate receptors. There is also evidence that CRF expressing CeA projection neurons to the bed nucleus of the stria terminalis (BNST) play an important role in stress related behaviors. Despite the potentially significant interactions between CRF and NMDA receptors in the CeA, the synaptic organization of these systems is largely unknown. Using dual labeling high resolution immunocytochemical electron microscopy, it was found that individual somata and dendrites displayed immunoreactivity for CRF and the NMDA-NR1 (NR1) subunit in the mouse CeA. In addition, CRF-containing axon terminals contacted postsynaptic targets in the CeA, some of which also expressed NR1. Neuronal profiles expressing the CRF type 1 receptor (CRF-R1), identified by the expression of green fluorescent protein (GFP) in bacterial artificial chromosome (BAC) transgenic mice, also contained NR1, and GFP immunoreactive terminals formed synapses with NR1 containing dendrites. Although CRF and GFP were only occasionally co-expressed in individual somata and dendritic profiles, contacts between labeled axon terminals and dendrites were frequently observed. A combination of tract tracing and immunocytochemistry revealed that a population of CeA CRF neurons projected to the BNST. It was also found that CRF, or GFP expressing terminals directly contacted CeA-BNST projection neurons. These results indicate that the NMDA receptor is positioned for the postsynaptic regulation of CRF expressing CeA neurons and the modulation of signals conveyed by CRF inputs. Interactions between CRF and NMDA receptor mediated signaling in CeA neurons, including those projecting to the BNST, may provide the synaptic basis for integrating the experience of stress and relevant environmental stimuli with behaviors that may be of particular relevance to stress-related learning and the emergence of psychiatric disorders, including drug addiction. SN - 1090-2430 UR - https://www.unboundmedicine.com/medline/citation/23063907/Corticotropin_releasing_factor_in_the_mouse_central_nucleus_of_the_amygdala:_ultrastructural_distribution_in_NMDA_NR1_receptor_subunit_expressing_neurons_as_well_as_projection_neurons_to_the_bed_nucleus_of_the_stria_terminalis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(12)00392-5 DB - PRIME DP - Unbound Medicine ER -