Del Pino I, García-Frigola C, Dehorter N, Brotons-Mas JR, Alvarez-Salvado E, Martínez de Lagrán M, Ciceri G, Gabaldón MV, Moratal D, Dierssen M, Canals S, Marín O, Rico B.
Erbb4 deletion from fast-spiking interneurons causes schizophrenia-like phenotypes. Neuron.
2013 Sep 18
Comments on News and Primary Papers
Comment by: Beatriz Rico
, Oscar Marin
Submitted 30 October 2013
Posted 5 November 2013
We would like to provide an answer to the question raised by Andrés Buonanno: “If the knockouts have more γ power, why do they perform less well on the Y maze?” As explained in the manuscript, the abnormal increase in γ power observed in conditional ErbB4 mutants would not necessarily lead to better performance, because interneurons are not pacing pyramidal cells at the proper/normal rhythm. In addition, local hypersynchrony seems to affect long-range functional connectivity: We showed a prominent decoupling between the hippocampus and prefrontal cortex. The increase in excitability and synchrony, and the decoupling between the hippocampus and prefrontal cortex, are likely the cause of the behavioral deficits in cognitive function.
In line with this, we respectfully disagree with Buonanno's next comment that “these data are also at odds with what has been observed in schizophrenia.” Indeed, as we mentioned in the manuscript, recent studies indicate that medication-naive, first-episode, and chronic patients with schizophrenia show elevated γ-band power in resting state. Baseline increases in γ oscillations are consistent with increases in the excitatory/inhibitory ratio of cortical neurons. Thus, cortical rhythm abnormalities in schizophrenia seem to include both abnormal increases in baseline power—as we observed in conditional ErbB4 mutants—as well as deficits in task-related oscillations (Uhlhaas and Singer, 2012).
Uhlhaas PJ, and Singer W. (2012). Neuronal dynamics and neuropsychiatric disorders: toward a translational paradigm for dysfunctional large-scale net- works. Neuron 75, 963–980. Abstract
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