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

Tae-Yeon Eom,Ildar T Bayazitov,Kara Anderson,Jing Yu,Stanislav S Zakharenko

doi:10.1016/j.celrep.2017.05.002

Tae-Yeon Eom, Ildar T Bayazitov + Show 3 more

Open Access

https://doi.org/10.1016/j.celrep.2017.05.002

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Journal: Cell Reports	Publication Date: May 1, 2017
Citations: 15	License type: cc-by

Affiliation: St. Jude Children's Research Hospital

Abstract

SummaryIndividuals 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.

Highlights

Emotions provide information about the present state of an individual based on previous experience and help guide future courses of action
We previously reported that the deletion of one copy of Dgcr8 impairs glutamatergic synaptic transmission at thalamic inputs to the auditory cortex by increasing the levels of dopamine receptors D2 (Drd2s) in the thalamus (Chun et al, 2014)
Because we have previously shown that microdeletion of 22q11DS genes increases Drd2 levels in the auditory thalamus (Chun et al, 2014) and that the auditory thalamus is important for the delivery of the CS to the amygdala—and for emotional memory—we hypothesized that fear memory is impaired in 22q11DS mice and that this deficit could be due to Dgcr8–Drd2-dependent impairment of synaptic transmission at thalamo-lateral amygdala (LA) projections

Summary

Introduction

Emotions provide information about the present state of an individual based on previous experience and help guide future courses of action. Patients with schizophrenia (SCZ) are impaired in their ability to anticipate or recall emotions (Engel et al, 2015; Gard et al, 2007; Kring and Elis, 2013). These deficits in emotional memory can be caused by impairments in memory consolidation processes for emotional stimuli and may contribute to the negative symptoms of SCZ, such as anhedonia or amotivation (Herbener et al, 2007). The neuronal circuits that underlie such deficits in emotional memory are not yet known

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