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Genetic deletion of the 67-kDa isoform of glutamate decarboxylase alters conditioned fear behavior in rats.

ABSTRACT: The GABAergic system is thought to play an important role in the control of cognition and emotion, such as fear, and is related to the pathophysiology of psychiatric disorders. For example, the expression of the 67-kDa isoform of glutamate decarboxylase (GAD67), a GABA-producing enzyme, is downregulated in the postmortem brains of patients with major depressive disorder and schizophrenia. However, knocking out the Gad1 gene, which encodes GAD67, is lethal in mice, and thus, the association between Gad1 and cognitive/emotional functions is unclear. We recently developed Gad1 knockout rats and found that some of them can grow into adulthood. Here, we performed fear-conditioning tests in adult Gad1 knockout rats to assess the impact of the loss of Gad1 on fear-related behaviors and the formation of fear memory. In a protocol assessing both cued and contextual memory, Gad1 knockout rats showed a partial antiphase pattern of freezing during training and significantly excessive freezing during the contextual test compared with wild-type rats. However, Gad1 knockout rats did not show any synchronous increase in freezing with auditory tones in the cued test. On the other hand, in a contextual memory specialized protocol, Gad1 knockout rats exhibited comparable freezing behavior to wild-type rats, while their fear extinction was markedly impaired. These results suggest that GABA synthesis by GAD67 has differential roles in cued and contextual fear memory.

SUBMITTER: Fujihara K

PROVIDER: S-EPMC7876494 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Genetic deletion of the 67-kDa isoform of glutamate decarboxylase alters conditioned fear behavior in rats.

Fujihara Kazuyuki K Sato Takumi T Miyasaka Yoshiki Y Mashimo Tomoji T Yanagawa Yuchio Y

FEBS open bio 20201230 2

The GABAergic system is thought to play an important role in the control of cognition and emotion, such as fear, and is related to the pathophysiology of psychiatric disorders. For example, the expression of the 67-kDa isoform of glutamate decarboxylase (GAD67), a GABA-producing enzyme, is downregulated in the postmortem brains of patients with major depressive disorder and schizophrenia. However, knocking out the Gad1 gene, which encodes GAD67, is lethal in mice, and thus, the association betwe ...[more]

PMID: 33325157

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Project description:Social support, when provided following a traumatic experience, is associated with a lower incidence of stress-related psychiatric disorders. Our hypothesis was that providing a social interaction period with a naive conspecific would improve sleep architecture in response to cued fear conditioning in Wistar rats. Rats were randomly assigned to either the socially isolated or socially partnered groups. Rats assigned to the socially isolated group were individually housed following electrode implantation and fear conditioning. Rats assigned to the socially partnered group were initially paired-housed, and then one rat from each pair was randomly chosen for sleep electrode implantation and fear conditioning. Rats from both groups were habituated to a recording chamber, and baseline sleep was recorded over 22 hours. One day later (Training Day), they were fear-conditioned to 10 presentations of a tone (800 Hz, 90 dB, 5 sec) co-terminating with a mild electric foot shock (1.0 mA, 0.5 sec), at 30-sec intervals. While rats in the socially isolated group were left undisturbed in their home cage for 30-min, socially partnered rats interacted for 30 minutes with their non-stressed rat partner immediately after fear conditioning and while the auditory tones were presented on Days 1 and 14. The results indicated that social interaction increased sleep efficiency in partnered rats compared to isolated rats following the fear conditioning procedure. This was due to an increase in the amount of rapid eye movement sleep (REMS) during the light phase. Evaluation of REMS microarchitecture revealed that the increase in REMS was due to an increase in the number of single REMS episodes (siREMS), which represented a more consolidated REMS pattern. A surprising finding was that partnered rats had a greater number of sequential REMS episodes (seqREMS) at Baseline, on the Training Day and on Day 1 when compared to isolated rats. The greater number of seqREMS episodes in partnered rats may be due to the partnering procedure and not fear conditioning, as the effect was also seen at Baseline. Thus it appears that while the partnering procedure may have given rise to a fragmented REMS pattern, social partnering promoted a greater consolidation of REMS in response to the fear conditioning procedure.

Dataset Information

Genetic deletion of the 67-kDa isoform of glutamate decarboxylase alters conditioned fear behavior in rats.

Publications

Genetic deletion of the 67-kDa isoform of glutamate decarboxylase alters conditioned fear behavior in rats.

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