Abolished ketamine effects on the spontaneous excitatory postsynaptic current of medial prefrontal cortex neurons in GluN2D knockout mice

AbstractKetamine, a non-competitive antagonist of the N-methyl-d-aspartate receptor (NMDAR), generates a rapidly-acting antidepressant effect. It exerts psychomimetic effects, yet demands a further investigation of its mechanism. Previous research showed that ketamine did no longer promote hyperlocomotion in GluN2D knockout (KO) mice, which is a subunit of NMDAR. In the present study, we tested whether GluN2D-containing NMDARs participate in the physiological changes in the medial prefrontal cortex (mPFC) triggered by ketamine. Sub-anesthetic dose of ketamine (25 mg/kg) elevated the frequency of spontaneous excitatory postsynaptic currents (sEPSC) in wild-type (WT) mice, but not in GluN2D KO mice, 1 h after the injection. The amplitude of sEPSC and paired-pulse ratio (PPR) were unaltered by ketamine in both WT and GluN2D KO mice. These findings suggest that GluN2D-containing NMDARs might play a role in the ketamine-mediated changes in glutamatergic neurons in mPFC and, presumably, in ketamine-induced hyperlocomotion.

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Antidepressant Effect of Optogenetic Stimulation of the Medial Prefrontal Cortex

Journal of Neuroscience ◽

10.1523/jneurosci.1731-10.2010 ◽

2010 ◽

Vol 30 (48) ◽

pp. 16082-16090 ◽

Cited By ~ 351

Author(s):

H. E. Covington ◽

M. K. Lobo ◽

I. Maze ◽

V. Vialou ◽

J. M. Hyman ◽

...

Keyword(s):

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Antidepressant Effect ◽

Optogenetic Stimulation ◽

Stimulation Of

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Activation of the prelimbic medial prefrontal cortex induces anxiety-like behaviors via N-Methyl-D-aspartate receptor-mediated glutamatergic neurotransmission in mice

Journal of Neuroscience Research ◽

10.1002/jnr.23391 ◽

2014 ◽

Vol 92 (8) ◽

pp. 1044-1053 ◽

Cited By ~ 29

Author(s):

Akiyoshi Saitoh ◽

Masanori Ohashi ◽

Satoshi Suzuki ◽

Mai Tsukagoshi ◽

Azusa Sugiyama ◽

...

Keyword(s):

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Glutamatergic Neurotransmission ◽

Aspartate Receptor

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Basolateral amygdala input to the medial prefrontal cortex controls obsessive-compulsive disorder-like checking behavior

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1814292116 ◽

2019 ◽

Vol 116 (9) ◽

pp. 3799-3804 ◽

Cited By ~ 10

Author(s):

Tingting Sun ◽

Zihua Song ◽

Yanghua Tian ◽

Wenbo Tian ◽

Chunyan Zhu ◽

...

Keyword(s):

Prefrontal Cortex ◽

Obsessive Compulsive Disorder ◽

Medial Prefrontal Cortex ◽

Basolateral Amygdala ◽

Obsessive Compulsive ◽

Neuronal Tracing ◽

Compulsive Disorder ◽

Glutamatergic Neurons ◽

Fmri Study ◽

Checking Behavior

Obsessive-compulsive disorder (OCD) affects ∼1 to 3% of the world’s population. However, the neural mechanisms underlying the excessive checking symptoms in OCD are not fully understood. Using viral neuronal tracing in mice, we found that glutamatergic neurons from the basolateral amygdala (BLAGlu) project onto both medial prefrontal cortex glutamate (mPFCGlu) and GABA (mPFCGABA) neurons that locally innervate mPFCGlu neurons. Next, we developed an OCD checking mouse model with quinpirole-induced repetitive checking behaviors. This model demonstrated decreased glutamatergic mPFC microcircuit activity regulated by enhanced BLAGlu inputs. Optical or chemogenetic manipulations of this maladaptive circuitry restored the behavioral response. These findings were verified in a mouse functional magnetic resonance imaging (fMRI) study, in which the BLA–mPFC functional connectivity was increased in OCD mice. Together, these findings define a unique BLAGlu→mPFCGABA→Glu circuit that controls the checking symptoms of OCD.

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Ventral hippocampal projections to the medial prefrontal cortex regulate social memory

10.1101/461533 ◽

2018 ◽

Cited By ~ 1

Author(s):

Mary L. Phillips ◽

Holly A. Robinson ◽

Lucas Pozzo-Miller

Keyword(s):

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Pyramidal Neurons ◽

Social Memory ◽

Memory Deficits ◽

Autism Spectrum ◽

Innervation Pattern ◽

Wild Type ◽

Contributing Factors ◽

Social Memories

SUMMARYInputs from the ventral hippocampus (vHIP) to the medial prefrontal cortex (mPFC) have been implicated in several neuropsychiatric disorders. Here, we show that the long-range vHIP-mPFC projection is hyperactive in the Mecp2 knockout (KO) mouse model of the autism spectrum disorder Rett syndrome, which has deficits in social memory. Chronically mimicking vHIP-mPFC hyperexcitability in wild-type mice impaired social memory, whereas chronic inhibition of mPFC-projecting vHIP neurons in Mecp2 KO mice rescued social memory deficits; the extent of memory rescue was negatively correlated with the strength of vHIP input to the mPFC. Acute manipulations of the vHIP-mPFC projection also affected social memory in a specific and selective manner, suggesting that proper vHIP-mPFC signaling is necessary to recall social memories. In addition, we identified an altered vHIP-mPFC innervation pattern and increased synaptic strength onto layer 5 pyramidal neurons as contributing factors in aberrant vHIP-mPFC signaling in Mecp2 KO mice.

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