Impaired fast-spiking interneuron function in a genetic mouse model of depression.
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.
Physiologisches Institut I, Systemic and Cellular Neurophysiology, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
Jonas-Frederic
JF
Sauer
Physiologisches Institut I, Systemic and Cellular Neurophysiology, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
Michael
M
Strüber
Physiologisches Institut I, Systemic and Cellular Neurophysiology, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
Marlene
M
Bartos
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal; D003863:Depression / Q000235:genetics* / Q000503:physiopathology*; D004195:Disease Models, Animal; D065818:Gamma Rhythm; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D008959:Models, Neurological; D009415:Nerve Net / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D017397:Prefrontal Cortex / Q000503:physiopathology; D013569:Synapses / Q000378:metabolism; D013826:Theta Rhythm
C498794:Disc1 protein, mouse; D009419:Nerve Tissue Proteins; D010320:Parvalbumins
Disc1; depression; interneuron; mouse; neuroscience; oscillation; parvalbumin; prefrontal cortex