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Impaired fast-spiking interneuron function in a genetic mouse model of depression.

Sauer JF, Strüber M, Bartos M - Elife (2015)

Bottom Line: The number of FS-INs is reduced, they receive fewer excitatory inputs, and form fewer release sites on targets.Computational analysis indicates that weak excitatory input and inhibitory output of FS-INs may lead to impaired gamma oscillations.Our data link network defects with a gene mutation underlying depression in humans.

View Article: PubMed Central - PubMed

Affiliation: Physiologisches Institut I, Systemic and Cellular Neurophysiology, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.

ABSTRACT
Rhythmic neuronal activity provides a frame for information coding by co-active cell assemblies. Abnormal brain rhythms are considered as potential pathophysiological mechanisms causing mental disease, but the underlying network defects are largely unknown. We find that mice expressing truncated Disrupted-in-Schizophrenia 1 (Disc1), which mirror a high-prevalence genotype for human psychiatric illness, show depression-related behavior. Theta and low-gamma synchrony in the prelimbic cortex (PrlC) is impaired in Disc1 mice and inversely correlated with the extent of behavioural despair. While weak theta activity is driven by the hippocampus, disturbance of low-gamma oscillations is caused by local defects of parvalbumin (PV)-expressing fast-spiking interneurons (FS-INs). The number of FS-INs is reduced, they receive fewer excitatory inputs, and form fewer release sites on targets. Computational analysis indicates that weak excitatory input and inhibitory output of FS-INs may lead to impaired gamma oscillations. Our data link network defects with a gene mutation underlying depression in humans.

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Related in: MedlinePlus

Unaltered sociability of Disc1 mice.(A) 3-chamber social interaction task. The mice explored the 3-chamber arena containing two empty (E) wire cups in a habituation run. In a second run, a stranger mouse (S) was placed in one of the cups (n = 9 each group). Right, examples of exploration paths. (B) Disc1 and control mice spent identical time in both compartments during habituation and more time with the stranger mouse in run two, indicating absent left-right preference and intact sociability, respectively. #p < 0.001. Data are mean ± SEM.DOI:http://dx.doi.org/10.7554/eLife.04979.007
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fig1s4: Unaltered sociability of Disc1 mice.(A) 3-chamber social interaction task. The mice explored the 3-chamber arena containing two empty (E) wire cups in a habituation run. In a second run, a stranger mouse (S) was placed in one of the cups (n = 9 each group). Right, examples of exploration paths. (B) Disc1 and control mice spent identical time in both compartments during habituation and more time with the stranger mouse in run two, indicating absent left-right preference and intact sociability, respectively. #p < 0.001. Data are mean ± SEM.DOI:http://dx.doi.org/10.7554/eLife.04979.007


Impaired fast-spiking interneuron function in a genetic mouse model of depression.

Sauer JF, Strüber M, Bartos M - Elife (2015)

Unaltered sociability of Disc1 mice.(A) 3-chamber social interaction task. The mice explored the 3-chamber arena containing two empty (E) wire cups in a habituation run. In a second run, a stranger mouse (S) was placed in one of the cups (n = 9 each group). Right, examples of exploration paths. (B) Disc1 and control mice spent identical time in both compartments during habituation and more time with the stranger mouse in run two, indicating absent left-right preference and intact sociability, respectively. #p < 0.001. Data are mean ± SEM.DOI:http://dx.doi.org/10.7554/eLife.04979.007
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4374525&req=5

fig1s4: Unaltered sociability of Disc1 mice.(A) 3-chamber social interaction task. The mice explored the 3-chamber arena containing two empty (E) wire cups in a habituation run. In a second run, a stranger mouse (S) was placed in one of the cups (n = 9 each group). Right, examples of exploration paths. (B) Disc1 and control mice spent identical time in both compartments during habituation and more time with the stranger mouse in run two, indicating absent left-right preference and intact sociability, respectively. #p < 0.001. Data are mean ± SEM.DOI:http://dx.doi.org/10.7554/eLife.04979.007
Bottom Line: The number of FS-INs is reduced, they receive fewer excitatory inputs, and form fewer release sites on targets.Computational analysis indicates that weak excitatory input and inhibitory output of FS-INs may lead to impaired gamma oscillations.Our data link network defects with a gene mutation underlying depression in humans.

View Article: PubMed Central - PubMed

Affiliation: Physiologisches Institut I, Systemic and Cellular Neurophysiology, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.

ABSTRACT
Rhythmic neuronal activity provides a frame for information coding by co-active cell assemblies. Abnormal brain rhythms are considered as potential pathophysiological mechanisms causing mental disease, but the underlying network defects are largely unknown. We find that mice expressing truncated Disrupted-in-Schizophrenia 1 (Disc1), which mirror a high-prevalence genotype for human psychiatric illness, show depression-related behavior. Theta and low-gamma synchrony in the prelimbic cortex (PrlC) is impaired in Disc1 mice and inversely correlated with the extent of behavioural despair. While weak theta activity is driven by the hippocampus, disturbance of low-gamma oscillations is caused by local defects of parvalbumin (PV)-expressing fast-spiking interneurons (FS-INs). The number of FS-INs is reduced, they receive fewer excitatory inputs, and form fewer release sites on targets. Computational analysis indicates that weak excitatory input and inhibitory output of FS-INs may lead to impaired gamma oscillations. Our data link network defects with a gene mutation underlying depression in humans.

Show MeSH
Related in: MedlinePlus