Social defeat drives hyperexcitation of the piriform cortex to induce learning and memory impairment but not mood-related disorders in mice

Abstract

Clinical studies have shown that social defeat is an important cause of mood-related disorders, accompanied by learning and memory impairment in humans. The mechanism of mood-related disorders has been widely studied. However, the specific neural network involved in learning and memory impairment caused by social defeat remains unclear. In this study, behavioral test results showed that the mice induced both learning and memory impairments and mood-related disorders after exposure to chronic social defeat stress (CSDS). c-Fos immunofluorescence and fiber photometry recording confirmed that CaMKIIα expressing neurons of the piriform cortex (PC) were selectively activated by exposure to CSDS. Next, chemogenetics and optogenetics were performed to activate PC CaMKIIα expressing neurons, which showed learning and memory impairment but not mood-related disorders. Furthermore, chemogenetic inhibition of PC CaMKIIα expressing neurons significantly alleviated learning and memory impairment induced by exposure to CSDS but did not relieve mood-related disorders. Therefore, our data suggest that the overactivation of PC CaMKIIα expressing neurons mediates CSDS-induced learning and memory impairment, but not mood-related disorders, and provides a potential therapeutic target for learning and memory impairment induced by social defeat.

Lateral hypothalamus orexinergic projection to the medial prefrontal cortex modulates chronic stress-induced anhedonia but not anxiety and despair

“…The mice were tested using multiple behavioral assays within a relatively short period and in the same consistent order. However, to minimize the possible carryover effects of the different behavioral tests, the sequence of the tests was arranged from the least to most stressful [ 13 , 25 ]. Therefore, further investigation is warranted to elucidate the specific roles of mPFC neurons in the amelioration of anhedonia.…”

“…Behavioral tests were conducted in conducted in order of increasing stimulus intensity. Due to the exploratory nature of this study, no formal power analysis or sample size estimation was conducted and the sample size estimation was based on prior experience [ 13 ].…”

“…The forced swimming test (FST) was performed according to a previously reported method [ 13 ]. Each mouse was introduced into a cylindrical tank (16 cm in diameter × 28 cm in height) filled with water to a depth of 20 cm.…”

“…Whole-cell patch-clamp recordings of the LH were performed according to a previously reported method [ 13 ]. Slices were transferred to a recording chamber perfused with O 2 -saturated ACSF at a rate of 2 ml/min (25 °C).…”

Lateral Septal Circuits Govern Schizophrenia-Like Effects of Ketamine on Social Behavior

“…The LS is primarily composed of GABAergic neurons, so chemogenetic activation of these neurons may reduce functional connectivity of the LS with brain regions like the piriform and caudate-putamen that receive these GABAergic inputs. While we cannot say for certain how LS inputs to the piriform shapes social behavior, the piriform cortex has been found to be hyperexcitable following social defeat, which is known to cause deficits in social interaction as well as learning and memory impairments [85]. Other studies suggest that downregulation of Oxtrs in the piriform cortex may contribute to social deficits in reelin haploinsufficient (+/-) mice, which have been used to model neurodevelopmental disorders including autism and schizophrenia [86].…”