Astrocytic Regulation of Neural Circuits Underlying Behaviors
Abstract
:1. Introduction
2. Olfactory Bulb
3. Prefrontal Cortex
4. Motor and Somatosensory Cortices
5. Anterior Cingulate Cortex
6. Hippocampus
7. Striatum
8. Amygdala
9. Thalamus
10. Hypothalamus
10.1. Arcuate Nucleus
10.2. Suprachiasmatic Nucleus
11. Midbrain
11.1. Ventral Tegmental Area
11.2. Periaqueductal Grey
12. Medulla Oblongata
13. Cerebellum
14. Spinal Cord
15. Concluding Remarks
Target Region | Manipulation | Change in Astrocytes | Consequence of Manipulation | Ref | |
---|---|---|---|---|---|
Circuit | Behavior | ||||
OB | Aldh1L1-cre mice/ GFAP: FLEX-hM3Dq | n.d. | Odor-evoked Ca2+ in M/Tsș↓ | Odor detection accuracy in Go/No-Go task↑ | [32] |
Aldh1L1-cre mice/ GFAP: FLEX-hM4Di | n.d. | Odor-evoked Ca2+ in M/Ts↑ | Odor detection accuracy in Go/No-Go task↓ | ||
PFC | WT mice/L-AAA (astrocyte-specific cytotoxin) | GFAP+ cells↓ | Progressive neuronal loss | Spatial memory in Morris water maze test↓ Reversal learning in attentional set-shifting task↓ | [35] |
WT mice/L-AAA | GFAP+ cells↓ | n.d. | Sucrose preference in SPT↓ Latency to feed in novelty suppressed feeding test↑ Immobility in FST↑ Escape latency in active avoidance test↑ | [25] | |
WT mice/DHK (GLT-1 inhibitor) | n.d. | n.d. | Intracranial self-stimulation threshold↑ Latency to begin drinking sucrose in sucrose intake test↑ | [26] | |
WT mice/ATP or ATP-γ-S | n.d. | n.d. | CSDS-induced social avoidance in SIT↓ CSDS-induced immobility in FST↓ CMS-induced fur condition↓ Post-CMS sucrose preference in SPT↑ | [24] | |
IP3R2−/− mice | ATP release↓ | n.d. | Immobility in FST↑ Fur condition↓ Sucrose consumption in SPT↓ | ||
GFAP-tTA;tetO-dnSNARE mice | ATP release↓ | n.d. | Immobility in FST↑ | ||
GFAP-tTA;tetO-MrgprA1 mice | ATP release↑ | n.d. | Immobility in FST↓ Social avoidance in SIT↓ | ||
WT mice/AAV GfaABC1D-hM3Dq | c-Fos+ cells↑ | n.d. | Ethanol consumption & preference↑ Locomotor activity (by low-dose ethanol)↑ Duration of LORR (by high-dose ethanol)↑ | [39] | |
WT mice/AAV GfaABC1D::hPMCA2w/b | c-Fos+ cells↓ | n.d. | Ethanol consumption, preference↓ Duration of LORR (high-dose ethanol)↓ | ||
MC | GLAST-creER;IP3R2fl/fl mice | Ca2+↓ | n.d. | Motor-skill learning in forelimb reaching task↓ | [40] |
WT mice/fluorocitrate (astrocyte metabolic inhibitor) | Ca2+↓ | LTP↓, GluA1↓ | Motor-skill learning in forelimb reaching task↓ | ||
SC | IP3R2−/− mice | Ca2+↓ | PSL-induced TSP-1 upregulation↓ | PSL-induced mechanical allodynia↓ | [41] |
WT mice/BAPTA-AM (Ca2+ chelator) | n.d. | PSL-induced mechanical allodynia↓ | |||
Fluoroacetate (astrocyte metabolic inhibitor) | n.d. | n.d. | PSL-induced mechanical allodynia↓ | ||
ACC | L-AAA | GFAP intensity↓ | n.d. | CFA-induced place escape/avoidance↓ | [27] |
GFAP-cre mice/ AAV CBA::FLEX-ChR2 | n.d. | n.d. | Non-rapid eye movement sleep↓ | [44] | |
WT mice/SNAP-5114 (GAT-3 inhibitor) | GAT-3 activity↓ | n.d. | PSL-induced sleep disturbance↓ | [45] | |
HP | WT mice/AAV GFAP::hM3Dq | Ca2+↑ | LTP↑ Neuronal c-Fos in CA1 (when learning is combined)↑ | Spatial memory in T-maze test↑ Contextual memory in fear conditioning test↑ | [47] |
WT mice/AAV GFAP::hM4Di | Ca2+↓ | CA3→CA1 synaptic transmission↓ CA1→ACC neuronal activity↓ | Remote contextual memory in fear conditioning test↓ | [48] | |
IL-1r−/− mice | n.d. | LTP↓ | Spatial memory in Morris water maze test↓ Contextual memory in fear conditioning test↓ | [50] | |
IL-1r−/− mice/transplantation of WT NPCs | n.d. | LTP↑ | Spatial memory in Morris water maze test↑ Contextual memory in fear conditioning test↑ | ||
GFAP-tTA;tetO-dnSNARE mice | n.d. | Sleep deprivation-induced LTP deficits↓ | Sleep deprivation-induced spatial memory impairment in SOR test↓ | [49] | |
WT mice/CPT (adenosine A1Rantagonist) | n.d. | Sleep deprivation-induced LTP deficits↓ | Sleep deprivation-induced spatial memory impairment in SOR test↓ | ||
AQP4−/− mice | n.d. | LTP↓ LTD↓ | Object recognition memory in object placement test↓ | [166] | |
GFAP-cre;Cx43fl/fl;Cx30−/− mice | Edema, vacuolation | Widespread edema, vacuolation (white matter) | Spatial memory in SOR test↓ Motor coordination in rotarod and balance beam assays↓ | [52] | |
STR | WT mice/AAV GfaABC1D::hPMCA2w/b | Ca2+↓ GAT-3↑ | Tonic GABA current↓ D1-MSN tonic inhibition↓ MSN excitability↓ | Duration of self-grooming↑ Travel distance in open field test↓ Time spent in center in open field test↓ | [55] |
WT mice/AAV GfaABC1D::hM4Di | Ca2+↑ TSP-1↑ | MSN EPSC↑ MSN firing↑ | Travel distance in open field test↑ Investigatory activity in light/dark open field test↓ Exploration of novel object in NOR test↓ | [56] | |
DRD1fl/fl mice/AAV GFAP::mCherry-cre | DA-evoked Ca2+↓ | DA-evoked synaptic depression↓ | Amphetamine-evoked locomotion enhancement↓ | [58] | |
IP3R2−/− mice | DA-evoked Ca2+↓ | DA-evoked synaptic depression↓ | Amphetamine-evoked locomotion enhancement↓ | ||
WT mice/AAV GFAP::hM3Dq | Intracellular Ca2+↑ ATP/adenosine release↑ | Synaptic depression↑ | n.d. | ||
AMY | WT mice/AAV GFAP::hM3Dq | Intracellular Ca2+↑ | BLA→CeM excitatory synaptic transmission↓(by A1R↑) CeL→CeM inhibitory synaptic transmission↑(by A2R↑) CeM neuronal firing↓ | Fear memory formation in fear conditioning tes↓ | [73] |
WT mice/DHK (GLT-1 inhibitor) | n.d. | n.d. | Intracranial self-stimulation threshold↑ Time spent in open arms in elevated plus maze test↓ Freezing behavior in fear conditioning test↑ | [74] | |
WT mice/TAT-Cx43L2 (Cx43-hemichannel blocker) | Cx43 activity↓ | No effects on synaptic release | Fear memory consolidation in fear conditioning test↓ | [75] | |
VB | WT mice/AAV Aldh1l1::cre and AAV pSico::DAO shRNA or AAV pSico::Aldh1a1 shRNA or AAV pSico::Best1 shRNA | Tonic GABA release↓ | Tonic GABA current↓ Temporal resolution↓ | Tactile discrimination in tactile-based NOR test↓ | [78] |
THIP (GABAAR agonist) | Intracellular Ca2+↑ Tonic GABA release↑ | Tonic GABA current↑ Temporal resolution of stimulation-evoked TC neuronal firing↑ | Tactile discrimination in tactile-based NOR test↑ | ||
LHb | WT rats/AAV GfaABC1D::Kir4.1 | RMP↓ | Extracellular K+↓ Neuronal RMP↓ Neuronal bursting↑ | Immobility in FST↑ Sucrose preference in SPT↓ | [79] |
WT rats/AAV H1::Kir4.1-shRNA or AAV GfaABC1D::dnKir4.1 | Neuronal bursting↓ | Immobility in FST↓ Bar pressing in learned helplessness test↑ Sucrose preference in SPT↑ | |||
ARH | GFAP-creERT2;Leprfl/fl mice | Number and length of projection↓ | Number of synapses onto POMC neurons↑ Glial coverage on the perikaryal membranes of POMC↓ mIPSC in POMC and AgRP neurons↑ mEPSC in AgRP neurons↑ | Leptin-induced suppression of food intake↓ Fasting- and ghrelin-induced food intake↑ | [84] |
WT mice/AAV GFAP::hM3Dq | n.d. | Activity of AgRP neurons↓ | Ghrelin-induced food intake↓ Leptin-induced suppression of food intake↓ | [85] | |
WT mice/AAV GFAP::hM4Di | n.d. | n.d. | Ghrelin-induced food intake↑ Leptin-induced suppression of food intake↓ | ||
WT mice/DPCPX (adenosine A1R antagonist) | n.d. | Activity of AgRP neurons↑ | Ghrelin-induced food intake↑ | ||
SCN | Aldh1L1-cre;Bmal1fl/fl mice | n.d. | Altered circadian oscillation | Altered circadian wheel-running activity | [89] |
GLAST-creERT2;Bmal1fl/fl mice | GAT-1, GAT-3↓ | Extracellular GABA level↑ Altered circadian oscillations of clock genes in neurons | Altered circadian wheel-running activity Cognitive deficits in NOR and SOL tests↑ | [90] | |
Cry1/2−/− mice/AAV GFAP::cre + AAV Cry1:: FLEX-Cry1 | Recovery of TTFL | Recovery of circadian oscillation of extracellular glutamate | Recovery of circadian locomotor activity | [91] | |
VTA | WT mice/AAV GfaABC1D::ChR2 | Na+, H+↑ K+↓ | GABAergic neuronal activity↑ Dopaminergic neuronal activity↓ | Real-time avoidance behavior in RTPP assay↑ Learned avoidance behavior in CPA assay↑ | [95] |
GLT-1fl/fl mice/ AAV GfaABC1D::ChR2 + AAV GfaABC1D::cre | n.d. | ChR2-induced increase in GABAergic neuronal activity↓ Dopaminergic neuronal activity↑ | ChR2-induced increase in learned avoidance behavior in CPA assay↓ | ||
PAG | WT mice/L-AAA (astrocytic cytotoxin) or SP600125 (JNK inhibitor) | BCP-induced GFAP upregulation↓ | n.d. | BCP-induced mechanical allodynia↓ | [98] |
PreBötC | WT rats/AAV sGFAP::hM3Dq | Intracellular Ca2+↑ Vesicle fusion events↑ ATP release↑ | n.d. | Resting respiratory rate↑ Frequency of sighs↑ | [110] |
WT rats/AAV sGFAP::dnSNARE or Tetanus toxin light chain (exocytosis inhibitor) | Vesicle fusion events↓ | n.d. | Resting respiratory rate↓ Frequency of sighs↓ | ||
CB | GLAST-creERT2; Gria1fl/fl;Gria4fl/fl mice | BG process retraction | EPSC frequency of PC↓ PF-PC synapse density↓ | Fine motor coordination in ELT and PECT↓ | [120] |
Best1−/− mice or MAOB−/− mice or WT mice/selegiline (MAOB inhibitor) | Tonic GABA release↓ | Excitability of GCs↑ PF-PC synaptic transmission↑ | Motor coordination in rotarod test↑ | [121] | |
GFAP-MAOB TG mice | Tonic GABA release↑ | Excitability of GCs↓ PF-PC synaptic transmission↓ | Motor coordination in rotarod test↓ | ||
Spinal cord | GFAP-cre;Stat3fl/fl mice or WT mice/AG490 (JAK inhibitor) | DCP-induced GFAP upregulation↓ DCP-induced LCN2 upregulation↓ | DCP-induced neuronal excitation↓ | DCP-induced scratching↓ | [122] |
Hoxb8-cre;GLT-1fl/fl mice | n.d. | n.d. | PSL-induced mechanical allodynia↑ | [124] | |
WT rats/AAV GfaABC1D::ChR2 | ATP release↑ | Adenosine A1R↑ Excitability of GABAergic interneurons↓ Excitability of NK1R+ projection neurons↑ | Mechanical allodynia↑ Thermal hyperalgesia↑ SNI-induced mechanical allodynia↑ | [128] |
Behavior | Target Region | Manipulation | Major Phenotype | Ref |
---|---|---|---|---|
Cognition | PFC | WT mice/L-AAA (astrocyte-specific cytotoxin) | Spatial memory in Morris water maze test↓ Reversal learning in attentional set-shifting task↓ | [35] |
ACC | GFAP-cre mice/ AAV CBA::FLEX-ChR2 | Non-rapid eye movement sleep↓ | [44] | |
HP | WT mice/AAV GFAP::hM3Dq | Spatial memory in T-maze test↑ Contextual memory in fear conditioning test↑ | [47] | |
WT mice/AAV GFAP::hM4Di | Remote contextual memory in fear conditioning test↓ | [48] | ||
IL-1r−/− mice | Spatial memory in Morris water maze test↓ Contextual memory in fear conditioning test↓ | [50] | ||
IL-1r−/− mice/transplantation of WT NPCs | Spatial memory in Morris water maze test↑ Contextual memory in fear conditioning test↑ | [50] | ||
GFAP-tTA;tetO-dnSNARE mice | Sleep deprivation-induced spatial memory impairment in SOR test↓ | [49] | ||
WT mice/CPT (adenosine A1 receptor antagonist) | Sleep deprivation-induced spatial memory impairment in SOR test↓ | [49] | ||
AQP4−/− mice | Object recognition memory in object placement test↓ | [166] | ||
GFAP-cre;Cx43fl/fl;Cx30−/− mice | Spatial memory in SOR test↓ | [52] | ||
AMY | WT mice/AAV GFAP::hM3Dq | Fear memory formation in fear conditioning test↓ | [73] | |
WT mice/DHK (GLT-1 inhibitor) | Freezing behavior in fear conditioning test↑ | [74] | ||
WT mice/TAT-Cx43L2 (Cx43-hemichannel blocker) | Fear memory consolidation in fear conditioning test↓ | [75] | ||
SCN | GLAST-creERT2;Bmal1fl/fl mice | Altered circadian wheel-running activity Cognitive deficits in NOR and SOL tests↑ | [90] | |
VTA | WT mice/AAV GfaABC1D::ChR2 | Real-time avoidance behavior in RTPP assay↑ Learned avoidance behavior in CPA assay↑ | [95] | |
GLT-1fl/fl mice/ AAV GfaABC1D: ChR2 + AAV GfaABC1D: cre | ChR2-induced increase in learned avoidance behavior in CPA assay↓ | [95] | ||
Circadian rhythm | SCN | Aldh1L1-cre;Bmal1fl/fl mice | Altered circadian wheel-running activity | [89] |
GLAST-creERT2;Bmal1fl/fl mice | Altered circadian wheel-running activity | [90] | ||
Cry1/2−/− mice/AAV GFAP::cre + AAV Cry1:: FLEX-Cry1 | Recovery of circadian locomotor activity | [91] | ||
Emotion | PFC | WT mice/L-AAA | Sucrose preference in SPT↓ Latency to feed in novelty suppressed feeding test↑ Immobility in FST↑ Escape latency in active avoidance test↑ | [25] |
WT mice/DHK (GLT-1 inhibitor) | Intracranial self-stimulation threshold↑ Latency to begin drinking sucrose in sucrose intake test↑ | [26] | ||
WT mice/ATP or ATP-γ-S | CSDS-induced social avoidance in SIT↓ CSDS-induced immobility in FST↓ CMS-induced fur condition↓ Post-CMS sucrose preference in SPT↑ | [24] | ||
IP3R2−/− mice | Immobility in FST↑ Fur condition↓ Sucrose consumption in SPT↓ | [24] | ||
GFAP-tTA;tetO-dnSNARE mice | Immobility in FST↑ | [24] | ||
GFAP-tTA;tetO-MrgprA1 mice | Immobility in FST↓ Social avoidance in SIT↓ | [24] | ||
STR | WT mice/AAV GfaABC1D::hPMCA2w/b | Duration of self-grooming↑ Travel distance in open field test↓ Time spent in center in open field test↓ | [55] | |
WT mice/AAV GfaABC1D::hM4Di | Travel distance in open field test↑ Investigatory activity in light/dark open field test↓ Exploration of novel object in NOR test↓ | [56] | ||
AMY | WT mice/DHK (GLT-1 inhibitor) | Intracranial self-stimulation threshold↑ Time spent in open arms in elevated plus maze test↓ | [74] | |
LHb | WT rats/AAV GfaABC1D::Kir4.1 | Immobility in FST↑ Sucrose preference in SPT↓ | [79] | |
WT rats/AAV H1::Kir4.1-shRNA or AAV GfaABC1D::dnKir4.1 | Immobility in FST↓ Bar pressing in learned helplessness test↑ Sucrose preference in SPT↑ | [79] | ||
Motor skill | MC | GLAST-creER;IP3R2fl/fl mice | Motor-skill learning in forelimb reaching task↓ | [40] |
WT mice/fluorocitrate (astrocyte metabolic inhibitor) | Motor-skill learning in forelimb reaching task↓ | [40] | ||
HP | GFAP-cre;Cx43fl/fl;Cx30−/− mice | Motor coordination in rotarod and balance beam assays↓ | [52] | |
CB | GLAST-creERT2;Gria1fl/fl;Gria4fl/fl mice | Fine motor coordination in ELT and PECT↓ | [120] | |
Best1−/− mice or MAOB−/− mice or WT mice/selegiline (MAOB inhibitor) | Motor coordination in rotarod test↑ | [121] | ||
GFAP-MAOB TG mice | Motor coordination in rotarod test↓ | [121] | ||
Sensory processing | OB | Aldh1L1-cre mice/ AAV GFAP::FLEX-hM3Dq | Odor detection accuracy in Go/No-Go task↑ | [32] |
Aldh1L1-cre mice/ AAV GFAP::FLEX-hM4Di | Odor detection accuracy in Go/No-Go task↓ | [32] | ||
SC | IP3R2−/− mice | PSL-induced mechanical allodynia↓ | [41] | |
WT mice/BAPTA-AM (Ca2+ chelator) | PSL-induced mechanical allodynia↓ | [41] | ||
Fluoroacetate (astrocyte metabolic inhibitor) | PSL-induced mechanical allodynia↓ | [41] | ||
ACC | L-AAA | CFA-induced place escape/avoidance↓ | [27] | |
WT mice/SNAP-5114 (GAT-3 inhibitor) | PSL-induced sleep disturbance↓ | [45] | ||
VB | WT mice/AAV Aldh1l1::cre and AAV pSico::DAO shRNA or AAV pSico::Aldh1a1 shRNA or AAV pSico::Best1 shRNA | Tactile discrimination in tactile-based NOR test↓ | [78] | |
THIP (GABAAR agonist) | Tactile discrimination in tactile-based NOR test↑ | [78] | ||
PAG | WT mice/L-AAA (astrocytic cytotoxin) or SP600125 (JNK inhibitor) | BCP-induced mechanical allodynia↓ | [98] | |
Spinal cord | GFAP-cre;Stat3fl/fl mice or WT mice/AG490 (JNK inhibitor) | DCP-induced scratching↓ | [122] | |
Hoxb8-cre;GLT-1fl/fl mice | PSL-induced mechanical allodynia↑ | [124] | ||
WT rats/AAV GfaABC1D::ChR2 | Mechanical allodynia Thermal hyperalgesia SNI-induced mechanical allodynia↑ | [128] | ||
Appetite | ARH | GFAP-creERT2;Leprfl/fl mice | Leptin-induced suppression of food intake↓ Fasting- and ghrelin-induced food intake↑ | [84] |
WT mice/AAV GFAP::hM3Dq | Ghrelin-induced food intake↓ Leptin-induced suppression of food intake↑ | [85] | ||
WT mice/AAV GFAP::hM4Di | Ghrelin-induced food intake↑ Leptin-induced suppression of food intake↓ | [85] | ||
WT mice/DPCPX (adenosine A1R antagonist) | Ghrelin-induced food intake↑ | [85] |
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Hwang, S.-N.; Lee, J.S.; Seo, K.; Lee, H. Astrocytic Regulation of Neural Circuits Underlying Behaviors. Cells 2021, 10, 296. https://doi.org/10.3390/cells10020296
Hwang S-N, Lee JS, Seo K, Lee H. Astrocytic Regulation of Neural Circuits Underlying Behaviors. Cells. 2021; 10(2):296. https://doi.org/10.3390/cells10020296
Chicago/Turabian StyleHwang, Sun-Nyoung, Jae Seung Lee, Kain Seo, and Hyosang Lee. 2021. "Astrocytic Regulation of Neural Circuits Underlying Behaviors" Cells 10, no. 2: 296. https://doi.org/10.3390/cells10020296
APA StyleHwang, S.-N., Lee, J. S., Seo, K., & Lee, H. (2021). Astrocytic Regulation of Neural Circuits Underlying Behaviors. Cells, 10(2), 296. https://doi.org/10.3390/cells10020296