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Inducing Plasticity of Astrocytic Receptors by Manipulation of Neuronal Firing Rates
Published on: March 20, 2014
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Astrocyte β-Adrenergic Receptor Activity Regulates NMDA Receptor Signaling of Medial Prefrontal Cortex Pyramidal
Armani P Del Franco1, Eric A Newman2
1Department of Neuroscience, University of Minnesota, Minneapolis 55455, Minnesota.
Summary
Norepinephrine (NE) and beta-adrenergic receptor (β-AR) signaling in astrocytes increase their process volume. This astrocyte activity reduces glutamate spillover and extrasynaptic NMDA receptor (NMDAR) activation in the medial prefrontal cortex.
Area of Science:
- Neuroscience
- Cellular Biology
- Neuropharmacology
Background:
- Astrocytes regulate synaptic glutamate levels, controlling extrasynaptic NMDA receptor (NMDAR) activation.
- Norepinephrine (NE) and β-adrenergic receptors (β-ARs) influence astrocyte function, but their role in glutamate spillover and NMDAR activity outside sensory areas is unknown.
- Astrocyte process dynamics are crucial for modulating synaptic transmission.
Purpose of the Study:
- To investigate the effect of noradrenergic signaling on astrocyte process volume in the medial prefrontal cortex.
- To determine how β-AR activation in astrocytes impacts glutamate spillover and neuronal NMDAR activity.
- To explore the role of astrocyte β-ARs in regulating extrasynaptic NMDAR currents.
Main Methods:
- Monitored astrocyte process volume changes in response to NE and isoproterenol (ISO) in mouse medial prefrontal cortex.
- Measured evoked NMDAR currents in Layer 5 pyramidal neurons under various stimulation and drug conditions (ISO, GDPβS, MK-801).
- Assessed the impact of β-AR signaling blockade in astrocytes on NMDAR currents during high-frequency stimulation.
Main Results:
- Both NE and ISO significantly increased astrocyte process volume by approximately 20%.
- ISO reduced NMDAR currents evoked by high-frequency stimulation (10 stimuli at 50 Hz), which causes glutamate spillover, by 18%.
- This reduction in NMDAR currents was also observed for extrasynaptic NMDARs and was reversed by blocking astrocyte β-AR signaling.
Conclusions:
- Astrocyte β-AR activation modulates astrocyte process volume in the medial prefrontal cortex.
- Noradrenergic signaling via astrocyte β-ARs reduces glutamate spillover.
- This astrocyte-mediated mechanism limits the recruitment of extrasynaptic NMDARs, impacting neuronal excitability.
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