PMID- 37989594
OWN - NLM
STAT- MEDLINE
DCOM- 20240112
LR  - 20240406
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 44
IP  - 2
DP  - 2024 Jan 10
TI  - Astrocyte beta-Adrenergic Receptor Activity Regulates NMDA Receptor Signaling of 
      Medial Prefrontal Cortex Pyramidal Neurons.
LID - 10.1523/JNEUROSCI.0990-23.2023 [doi]
LID - e0990232023
AB  - Glutamate spillover from the synapse is tightly regulated by astrocytes, limiting 
      the activation of extrasynaptically located NMDA receptors (NMDAR). The processes 
      of astrocytes are dynamic and can modulate synaptic physiology. Though 
      norepinephrine (NE) and beta-adrenergic receptor (beta-AR) activity can modify 
      astrocyte volume, this has yet to be confirmed outside of sensory cortical areas, 
      nor has the effect of noradrenergic signaling on glutamate spillover and neuronal 
      NMDAR activity been explored. We monitored changes to astrocyte process volume in 
      response to noradrenergic agonists in the medial prefrontal cortex of male and 
      female mice. Both NE and the beta-AR agonist isoproterenol (ISO) increased process 
      volume by  approximately 20%, significantly higher than changes seen when astrocytes had 
      G-protein signaling blocked by GDPbetaS. We measured the effect of beta-AR signaling on 
      evoked NMDAR currents. While ISO did not affect single stimulus excitatory 
      currents of Layer 5 pyramidal neurons, ISO reduced NMDAR currents evoked by 10 
      stimuli at 50 Hz, which elicits glutamate spillover, by 18%. After isolating 
      extrasynaptic NMDARs by blocking synaptic NMDARs with the activity-dependent 
      NMDAR blocker MK-801, ISO similarly reduced extrasynaptic NMDAR currents in 
      response to 10 stimuli by 18%. Finally, blocking beta-AR signaling in the astrocyte 
      network by loading them with GDPbetaS reversed the ISO effect on 10 stimuli-evoked 
      NMDAR currents. These results demonstrate that astrocyte beta-AR activity reduces 
      extrasynaptic NMDAR recruitment, suggesting that glutamate spillover is reduced.
CI  - Copyright (c) 2024 the authors.
FAU - Del Franco, Armani P
AU  - Del Franco AP
AD  - Department of Neuroscience, University of Minnesota, Minneapolis 55455, 
      Minnesota.
FAU - Newman, Eric A
AU  - Newman EA
AUID- ORCID: 0000-0002-9296-6237
AD  - Department of Neuroscience, University of Minnesota, Minneapolis 55455, Minnesota 
      ean@umn.edu.
LA  - eng
GR  - R01 NS126166/NS/NINDS NIH HHS/United States
PT  - Journal Article
DEP - 20240110
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 0 (Receptors, Adrenergic, beta)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Male
MH  - Female
MH  - *Receptors, N-Methyl-D-Aspartate/metabolism
MH  - *Astrocytes/metabolism
MH  - Pyramidal Cells/physiology
MH  - Prefrontal Cortex/physiology
MH  - Glutamic Acid/physiology
MH  - Receptors, Adrenergic, beta
MH  - Synapses/physiology
PMC - PMC10860478
OTO - NOTNLM
OT  - astrocyte
OT  - extrasynaptic NMDA receptors
OT  - glia modulation of synapses
OT  - norepinephrine
OT  - synaptic modulation
OT  - beta-adrenergic receptors
EDAT- 2023/11/22 00:42
MHDA- 2024/01/12 06:43
PMCR- 2024/07/10
CRDT- 2023/11/21 21:43
PHST- 2023/05/29 00:00 [received]
PHST- 2023/10/23 00:00 [revised]
PHST- 2023/11/13 00:00 [accepted]
PHST- 2024/07/10 00:00 [pmc-release]
PHST- 2024/01/12 06:43 [medline]
PHST- 2023/11/22 00:42 [pubmed]
PHST- 2023/11/21 21:43 [entrez]
AID - JNEUROSCI.0990-23.2023 [pii]
AID - jneuro-44-e0990232023 [pii]
AID - 10.1523/JNEUROSCI.0990-23.2023 [doi]
PST - epublish
SO  - J Neurosci. 2024 Jan 10;44(2):e0990232023. doi: 10.1523/JNEUROSCI.0990-23.2023.