Schizophrenia-Related Microdeletion Impairs Emotional Memory through MicroRNA-Dependent Disruption of Thalamic Inputs to the Amygdala

Publication date: 23 May 2017
Source:Cell Reports, Volume 19, Issue 8
Author(s): Tae-Yeon Eom, Ildar T. Bayazitov, Kara Anderson, Jing Yu, Stanislav S. Zakharenko
Individuals with 22q11.2 deletion syndrome (22q11DS) are at high risk of developing psychiatric diseases such as schizophrenia. Individuals with 22q11DS and schizophrenia are impaired in emotional memory, anticipating, recalling, and assigning a correct context to emotions. The neuronal circuits responsible for these emotional memory deficits are unknown. Here, we show that 22q11DS mouse models have disrupted synaptic transmission at thalamic inputs to the lateral amygdala (thalamo-LA projections). This synaptic deficit is caused by haploinsufficiency of the 22q11DS gene Dgcr8, which is involved in microRNA processing, and is mediated by the increased dopamine receptor Drd2 levels in the thalamus and by reduced probability of glutamate release from thalamic inputs. This deficit in thalamo-LA synaptic transmission is sufficient to cause fear memory deficits. Our results suggest that dysregulation of the Dgcr8–Drd2 mechanism at thalamic inputs to the amygdala underlies emotional memory deficits in 22q11DS.

Graphical abstract

Teaser

Eom et al. show that mouse models of schizophrenia-associated 22q11.2 deletion syndrome are deficient in synaptic transmission at thalamic inputs to the lateral amygdala (LA). Thalamo-LA synaptic deficits impair fear memory and are mediated by Dgcr8 haploinsufficiency and Drd2 elevation in the auditory thalamus.


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