Presynaptic inhibition of gamma-aminobutyric acid release in the bed nucleus of the stria terminalis by kappa opioid receptor signaling.
BACKGROUND
The kappa opioid receptor (KOR) and its endogenous agonist, the neuropeptide dynorphin, are a critical component of the central stress system. Both dynorphin and KOR are expressed in the bed nucleus of the stria terminalis (BNST), a brain region associated with anxiety and stress. This suggests that KOR activation in this region may play a role in the regulation of emotional behaviors. To date, however, there has been no investigation of the ability of KOR to modulate synaptic transmission in the BNST.


METHODS
We used whole-cell patch-clamp recordings from acutely prepared mouse brain slices to examine the actions of KOR on inhibitory transmission in the BNST. Additionally, we used neurochemical and pathway-specific optogenetic manipulations to selectively stimulate gamma-aminobutyric acid (GABA)ergic fibers from the central nucleus of the amygdala (CeA) to the BNST.


RESULTS
We found that activation of KOR reduced GABAergic transmission through a presynaptic mechanism. Furthermore, we examined the signal transduction pathways that mediate this inhibition and provide the first functional information implicating extracellular signal-regulated kinase in KOR-mediated presynaptic modulation. Moreover, we found that at KOR signaling robustly reduced inhibitory synaptic transmission in the CeA to BNST pathway.


CONCLUSIONS
Together, these results demonstrate that KOR provides important inhibitory control over presynaptic GABAergic signaling within the BNST and provides the first direct functional demonstration of KOR-sensitive long-range GABAergic connections between the CeA and the BNST.
Curriculum in Neurobiology, School of Medicine, University of North Carolina-Chapel Hill, NC 27599, USA.
Chia
C
Li
Kristen E
KE
Pleil
Alice M
AM
Stamatakis
Steven
S
Busan
Linh
L
Vong
Bradford B
BB
Lowell
Garret D
GD
Stuber
Thomas L
TL
Kash
D000679:Amygdala / Q000378:metabolism; D000818:Animals; D004399:Dynorphins / Q000378:metabolism*; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D012686:Septal Nuclei / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D017473:Receptors, Opioid, kappa; D005680:gamma-Aminobutyric Acid; D004399:Dynorphins; D020928:Mitogen-Activated Protein Kinases