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

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.

VDR Potentiation and NMDA R Inhibition Facilitates Axo-Dendritic Process Formation in Melanocyte Model for Pigmented Cells in Parkinsonism

“…Most of the effects of the VDRA were restricted to process formation around the cell body; this is similar to the microtubule cytoskeletal system found in the dendritic nucleation assembly. This finding confirms the presence of VDR and its likely restriction to d cell body plus its role in facilitating short dendrite like process formation while NMDA R is located on the processes and facilitates long process formation; similar to the findings of Beckerman et al [37].…”

Stress increases GABAergic neurotransmission in CRF neurons of the central amygdala and bed nucleus stria terminalis

“…This study directly measured these 16 parameters and compared them to CRF-R1 lacking neurons (eGFP -). Our results 17 suggest that many CRF + neurons share some of these properties with CRF-R1 neurons 18 suggesting a partial overlap in these populations of genetically identified neurons 19(Beckerman et al, 2013). 20 CRF release in the extended amygdala has typically been associated with high-21 frequency, long duration firing of neurons; along with modulatory actions through G-22 protein coupled receptors (Rainnie et al, 1992; Yu and Shinnick-Gallagher, 1998)that the CRF-R1 antagonist, antalarmin, failed to affect light evoked IPSCs 1 in CRF -neurons in BnST and CeA.…”

Grin1 deletion in CRF neurons sex-dependently enhances fear, sociability, and social stress responsivity

“…Further, we and others have reported that CRF antagonism in the bed nucleus of the stria terminalis (BNST) can block the behavioral expression of social defeat (Cooper and Huhman, 2005;Jasnow et al, 2004b). This brain region receives heavy innervation from the CeA by neurons co-expressing CRF and Grin1 (glutamate receptor, ionotropic N-methyl-D-aspartate 1; NR1) receptor subunits (Beckerman et al, 2013). Blockade of this CRF-ergic projection also attenuates the behavioral effects of social defeat (Jasnow et al, 2004b).…”