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mGluR₁,5 activation improves network asynchrony and GABAergic synapse attenuation in the amygdala: implication for anxiety-like behavior in DBA/2 mice.

Zhang F, Liu B, Lei Z, Wang JH - Mol Brain (2012)

Bottom Line: Anxiety is a prevalent psychological disorder, in which the atypical expression of certain genes and the abnormality of amygdala are involved.Using behavioral task, two-photon cellular imaging and electrophysiology, we studied the characteristics of neural networks in basolateral amygdala and the influences of metabotropic glutamate receptor (mGluR) on their dynamics in DBA/2 mice showing anxiety-related genetic defects.The activity asynchrony of amygdala neurons and the weakness of GABA synaptic transmission are associated with anxiety-like behavior.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, China.

ABSTRACT
Anxiety is a prevalent psychological disorder, in which the atypical expression of certain genes and the abnormality of amygdala are involved. Intermediate processes between genetic defects and anxiety, pathophysiological characteristics of neural network, remain unclear. Using behavioral task, two-photon cellular imaging and electrophysiology, we studied the characteristics of neural networks in basolateral amygdala and the influences of metabotropic glutamate receptor (mGluR) on their dynamics in DBA/2 mice showing anxiety-related genetic defects. Amygdala neurons in DBA/2 high anxiety mice express asynchronous activity and diverse excitability, and their GABAergic synapses demonstrate weak transmission, compared to those in low anxiety FVB/N mice. mGluR1,5 activation improves the anxiety-like behaviors of DBA/2 mice, synchronizes the activity of amygdala neurons and strengthens the transmission of GABAergic synapses. The activity asynchrony of amygdala neurons and the weakness of GABA synaptic transmission are associated with anxiety-like behavior.

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The effect of 3,5-DHPG on the synchronous activity of amygdala neurons in DBA/2 mice. Oregon-green BAPTA-AM was loaded into the cells in brain slices including amygdala to monitor Ca2+ levels in neurons. OGB-1 in amygdala were excited and detected by a two-photon laser scanning microscopy before and after DHPG (10 μM) was washed onto the slices. A ~ B) The pictures of chip patterns show the cross-correlations in the timing phase of activity between neighboring neurons under the conditions of control (A) and 3,5-DHPG wash-on (B). Color red presents a high cross-correlation (synchronous activity). C) shows a comparison in correlation coefficients averaged from all of the visible amygdala neurons before (black symbols/line) and after (red) washing 3,5-DHPG to a slice from a DBA/2 mouse (p < 0.01). D) illustrates correlation coefficients averaged from all of experimental DBA/2 mice (n = 7) before (black symbols and line) and after (red) washing-on DHPG (p < 0.01). E) shows the comparison in the number of cells vs. their absolute fluorescence intensity (AFI) before (gray bars/fitting curve) and after applying DHPG (white bars/black curve) in DBA/2 mice. F) shows a comparison in the number of spontaneous events versus their relative fluorescence intensity (ΔF/F) before (gray bars/fitting curve) and after applying DHPG (white bars/black curve) in DBA/2 mice.
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Figure 8: The effect of 3,5-DHPG on the synchronous activity of amygdala neurons in DBA/2 mice. Oregon-green BAPTA-AM was loaded into the cells in brain slices including amygdala to monitor Ca2+ levels in neurons. OGB-1 in amygdala were excited and detected by a two-photon laser scanning microscopy before and after DHPG (10 μM) was washed onto the slices. A ~ B) The pictures of chip patterns show the cross-correlations in the timing phase of activity between neighboring neurons under the conditions of control (A) and 3,5-DHPG wash-on (B). Color red presents a high cross-correlation (synchronous activity). C) shows a comparison in correlation coefficients averaged from all of the visible amygdala neurons before (black symbols/line) and after (red) washing 3,5-DHPG to a slice from a DBA/2 mouse (p < 0.01). D) illustrates correlation coefficients averaged from all of experimental DBA/2 mice (n = 7) before (black symbols and line) and after (red) washing-on DHPG (p < 0.01). E) shows the comparison in the number of cells vs. their absolute fluorescence intensity (AFI) before (gray bars/fitting curve) and after applying DHPG (white bars/black curve) in DBA/2 mice. F) shows a comparison in the number of spontaneous events versus their relative fluorescence intensity (ΔF/F) before (gray bars/fitting curve) and after applying DHPG (white bars/black curve) in DBA/2 mice.

Mentions: If the asynchronous activity of network neurons is involved in anxiety-like behavior, we expect to see that mGluR activation synchronizes the activities of neurons in DBA/2 anxiety-like mice. We tested this assumption in the network neurons of amygdala slices, in which the temporal and spatial activity patterns of amygdala neurons were examined by two-photon cellular imaging (Method). Fluorescents in amygdala areas were excited and detected by a two-photon laser scanning microscopy before and after 3,5-DHPG (10 μM) was washed into the slices from DBA/2 mice. Chip patterns (cross-correlations, Figure 8A-B) show the time phase of activity between neighboring amygdala neurons from a DBA/2 mouse before and after using 3,5-DHPG. Colors from blue to red indicate their cross-correlations from low (asynchronous activity) to high (synchronous one). Figure 8C shows the correlation coefficients averaged from visible amygdala neurons in a slice from DBA/2 mouse under the conditions of control (black symbols/line) and DHPG (red, p < 0.01). Figure 8D illustrates the correlation coefficients averaged from all experimental DBA/2 mice (n = 6 for mice and n = 12 for slices) before (black symbols/line) and after (red) applying 3,5-DHPG (p < 0.01). Thus, the activation of mGluR1,5 improves the asynchronous activity of amygdala network neurons in DBA/2 anxiety-like mice.


mGluR₁,5 activation improves network asynchrony and GABAergic synapse attenuation in the amygdala: implication for anxiety-like behavior in DBA/2 mice.

Zhang F, Liu B, Lei Z, Wang JH - Mol Brain (2012)

The effect of 3,5-DHPG on the synchronous activity of amygdala neurons in DBA/2 mice. Oregon-green BAPTA-AM was loaded into the cells in brain slices including amygdala to monitor Ca2+ levels in neurons. OGB-1 in amygdala were excited and detected by a two-photon laser scanning microscopy before and after DHPG (10 μM) was washed onto the slices. A ~ B) The pictures of chip patterns show the cross-correlations in the timing phase of activity between neighboring neurons under the conditions of control (A) and 3,5-DHPG wash-on (B). Color red presents a high cross-correlation (synchronous activity). C) shows a comparison in correlation coefficients averaged from all of the visible amygdala neurons before (black symbols/line) and after (red) washing 3,5-DHPG to a slice from a DBA/2 mouse (p < 0.01). D) illustrates correlation coefficients averaged from all of experimental DBA/2 mice (n = 7) before (black symbols and line) and after (red) washing-on DHPG (p < 0.01). E) shows the comparison in the number of cells vs. their absolute fluorescence intensity (AFI) before (gray bars/fitting curve) and after applying DHPG (white bars/black curve) in DBA/2 mice. F) shows a comparison in the number of spontaneous events versus their relative fluorescence intensity (ΔF/F) before (gray bars/fitting curve) and after applying DHPG (white bars/black curve) in DBA/2 mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475049&req=5

Figure 8: The effect of 3,5-DHPG on the synchronous activity of amygdala neurons in DBA/2 mice. Oregon-green BAPTA-AM was loaded into the cells in brain slices including amygdala to monitor Ca2+ levels in neurons. OGB-1 in amygdala were excited and detected by a two-photon laser scanning microscopy before and after DHPG (10 μM) was washed onto the slices. A ~ B) The pictures of chip patterns show the cross-correlations in the timing phase of activity between neighboring neurons under the conditions of control (A) and 3,5-DHPG wash-on (B). Color red presents a high cross-correlation (synchronous activity). C) shows a comparison in correlation coefficients averaged from all of the visible amygdala neurons before (black symbols/line) and after (red) washing 3,5-DHPG to a slice from a DBA/2 mouse (p < 0.01). D) illustrates correlation coefficients averaged from all of experimental DBA/2 mice (n = 7) before (black symbols and line) and after (red) washing-on DHPG (p < 0.01). E) shows the comparison in the number of cells vs. their absolute fluorescence intensity (AFI) before (gray bars/fitting curve) and after applying DHPG (white bars/black curve) in DBA/2 mice. F) shows a comparison in the number of spontaneous events versus their relative fluorescence intensity (ΔF/F) before (gray bars/fitting curve) and after applying DHPG (white bars/black curve) in DBA/2 mice.
Mentions: If the asynchronous activity of network neurons is involved in anxiety-like behavior, we expect to see that mGluR activation synchronizes the activities of neurons in DBA/2 anxiety-like mice. We tested this assumption in the network neurons of amygdala slices, in which the temporal and spatial activity patterns of amygdala neurons were examined by two-photon cellular imaging (Method). Fluorescents in amygdala areas were excited and detected by a two-photon laser scanning microscopy before and after 3,5-DHPG (10 μM) was washed into the slices from DBA/2 mice. Chip patterns (cross-correlations, Figure 8A-B) show the time phase of activity between neighboring amygdala neurons from a DBA/2 mouse before and after using 3,5-DHPG. Colors from blue to red indicate their cross-correlations from low (asynchronous activity) to high (synchronous one). Figure 8C shows the correlation coefficients averaged from visible amygdala neurons in a slice from DBA/2 mouse under the conditions of control (black symbols/line) and DHPG (red, p < 0.01). Figure 8D illustrates the correlation coefficients averaged from all experimental DBA/2 mice (n = 6 for mice and n = 12 for slices) before (black symbols/line) and after (red) applying 3,5-DHPG (p < 0.01). Thus, the activation of mGluR1,5 improves the asynchronous activity of amygdala network neurons in DBA/2 anxiety-like mice.

Bottom Line: Anxiety is a prevalent psychological disorder, in which the atypical expression of certain genes and the abnormality of amygdala are involved.Using behavioral task, two-photon cellular imaging and electrophysiology, we studied the characteristics of neural networks in basolateral amygdala and the influences of metabotropic glutamate receptor (mGluR) on their dynamics in DBA/2 mice showing anxiety-related genetic defects.The activity asynchrony of amygdala neurons and the weakness of GABA synaptic transmission are associated with anxiety-like behavior.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, China.

ABSTRACT
Anxiety is a prevalent psychological disorder, in which the atypical expression of certain genes and the abnormality of amygdala are involved. Intermediate processes between genetic defects and anxiety, pathophysiological characteristics of neural network, remain unclear. Using behavioral task, two-photon cellular imaging and electrophysiology, we studied the characteristics of neural networks in basolateral amygdala and the influences of metabotropic glutamate receptor (mGluR) on their dynamics in DBA/2 mice showing anxiety-related genetic defects. Amygdala neurons in DBA/2 high anxiety mice express asynchronous activity and diverse excitability, and their GABAergic synapses demonstrate weak transmission, compared to those in low anxiety FVB/N mice. mGluR1,5 activation improves the anxiety-like behaviors of DBA/2 mice, synchronizes the activity of amygdala neurons and strengthens the transmission of GABAergic synapses. The activity asynchrony of amygdala neurons and the weakness of GABA synaptic transmission are associated with anxiety-like behavior.

Show MeSH
Related in: MedlinePlus