TY  - JOUR
A1  - Wagner-Altendorf, Tobias Alexander
A1  - Fischer, Beatrice
A1  - Roeper, Jochen
T1  - Axonal projection-specific differences in somatodendritic α2 autoreceptor function in locus coeruleus neurons
T2  - European journal of neuroscience
N2  - The locus coeruleus (LC) contains the majority of central noradrenergic neurons sending wide projections throughout the entire CNS. The LC is considered to be essential for multiple key brain functions including arousal, attention and adaptive stress responses as well as higher cognitive functions and memory. Electrophysiological studies of LC neurons have identified several characteristic functional features such as low-frequency pacemaker activity with broad action potentials, transient high-frequency burst discharges in response to salient stimuli and an apparently homogeneous inhibition of firing by activation of somatodendritic α2 autoreceptors (α2AR). While stress-mediated plasticity of the α2AR response has been described, it is currently unclear whether different LC neurons projecting to distinct axonal targets display differences in α2AR function. Using fluorescent beads-mediated retrograde tracing in adult C57Bl6/N mice, we compared the anatomical distributions and functional in vitro properties of identified LC neurons projecting either to medial prefrontal cortex, hippocampus or cerebellum. The functional in vitro analysis of LC neurons confirmed their mostly uniform functional properties regarding action potential generation and pacemaker firing. However, we identified significant differences in tonic and evoked α2AR-mediated responses. While hippocampal-projecting LC neurons were partially inhibited by endogenous levels of norepinephrine and almost completely silenced by application of saturating concentrations of the α2 agonist clonidine, prefrontal-projecting LC neurons were not affected by endogenous levels of norepinephrine and only partially inhibited by saturating concentrations of clonidine. Thus, we identified a limited α2AR control of electrical activity for prefrontal-projecting LC neurons indicative of functional heterogeneity in the LC-noradrenergic system.
KW  - alpha receptor
KW  - hippocampus
KW  - noradrenaline
KW  - norepinephrine
KW  - prefrontal cortex
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63810
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-638107
SN  - 1460-9568
N1  - Research was supported by funding to JR (CRC1080, DFG and Gutenberg Research College).
N1  - The peer review history for this article is available at https://publons.com/publon/10.1111/EJN.14553.
VL  - 50
IS  - 11
SP  - 3772
EP  - 3785
PB  - Wiley
CY  - Oxford [u.a.]
ER  -