scholarly journals IQSEC2 Deficiency Results in Abnormal Social Behaviors Relevant to Autism by Affecting Functions of Neural Circuits in the Medial Prefrontal Cortex

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2724
Author(s):  
Anuradha Mehta ◽  
Yoshinori Shirai ◽  
Emi Kouyama-Suzuki ◽  
Mengyun Zhou ◽  
Takahiro Yoshizawa ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Neurodevelopmental Disorders ◽  
Pyramidal Neurons ◽  
Synaptic Function ◽  
Electrophysiological Recording ◽  
Social Deficits ◽  
Nucleotide Exchange ◽  
Acid Receptor ◽  
Nucleotide Exchange Factor

IQSEC2 is a guanine nucleotide exchange factor (GEF) for ADP-ribosylation factor 6 (Arf6), of which protein is exclusively localized to the postsynaptic density of the excitatory synapse. Human genome studies have revealed that the IQSEC2 gene is associated with X-linked neurodevelopmental disorders, such as intellectual disability (ID), epilepsy, and autism. In this study, we examined the behavior and synapse function in IQSEC2 knockout (KO) mice that we generated using CRIPSR/Cas9-mediated genome editing to solve the relevance between IQSEC2 deficiency and the pathophysiology of neurodevelopmental disorders. IQSEC2 KO mice exhibited autistic behaviors, such as overgrooming and social deficits. We identified that up-regulation of c-Fos expression in the medial prefrontal cortex (mPFC) induced by social stimulation was significantly attenuated in IQSEC2 KO mice. Whole cell electrophysiological recording identified that synaptic transmissions mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), N-methyl-D-aspartate receptor (NMDAR), and γ-aminobutyric acid receptor (GABAR) were significantly decreased in pyramidal neurons in layer 5 of the mPFC in IQSEC2 KO mice. Reexpression of IQSEC2 isoform 1 in the mPFC of IQSEC2 KO mice using adeno-associated virus (AAV) rescued both synaptic and social deficits, suggesting that impaired synaptic function in the mPFC is responsible for social deficits in IQSEC2 KO mice.

scholarly journals Developmental Regulation of Basket Interneuron Synapses and Behavior through NCAM in Mouse Prefrontal Cortex

2020 ◽  
Vol 30 (8) ◽  
pp. 4689-4707
Author(s):  
Chelsea S Sullivan ◽  
Vishwa Mohan ◽  
Paul B Manis ◽  
Sheryl S Moy ◽  
Young Truong ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Pyramidal Neurons ◽  
Developmental Regulation ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Electrophysiological Recording ◽  
Network Function ◽  
Growth Cone Collapse ◽  
Layer 2 ◽  
And Behavior

Abstract Parvalbumin (PV)-expressing basket interneurons in the prefrontal cortex (PFC) regulate pyramidal cell firing, synchrony, and network oscillations. Yet, it is unclear how their perisomatic inputs to pyramidal neurons are integrated into neural circuitry and adjusted postnatally. Neural cell adhesion molecule NCAM is expressed in a variety of cells in the PFC and cooperates with EphrinA/EphAs to regulate inhibitory synapse density. Here, analysis of a novel parvalbumin (PV)-Cre: NCAM F/F mouse mutant revealed that NCAM functions presynaptically in PV+ basket interneurons to regulate postnatal elimination of perisomatic synapses. Mutant mice exhibited an increased density of PV+ perisomatic puncta in PFC layer 2/3, while live imaging in mutant brain slices revealed fewer puncta that were dynamically eliminated. Furthermore, EphrinA5-induced growth cone collapse in PV+ interneurons in culture depended on NCAM expression. Electrophysiological recording from layer 2/3 pyramidal cells in mutant PFC slices showed a slower rise time of inhibitory synaptic currents. PV-Cre: NCAM F/F mice exhibited impairments in working memory and social behavior that may be impacted by altered PFC circuitry. These findings suggest that the density of perisomatic synapses of PV+ basket interneurons is regulated postnatally by NCAM, likely through EphrinA-dependent elimination, which is important for appropriate PFC network function and behavior.

scholarly journals Development of inhibitory synaptic inputs on layer 2/3 pyramidal neurons in the rat medial prefrontal cortex

2018 ◽  
Author(s):  
Mari A. Virtanen ◽  
Claudia Marvine Lacoh ◽  
Hubert Fiumelli ◽  
Markus Kosel ◽  
Shiva Tyagarajan ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Pyramidal Neurons ◽  
Synaptic Inputs ◽  
Layer 2

scholarly journals Noradrenaline enhances the excitatory effects of dopamine on medial prefrontal cortex pyramidal neurons in rats

2020 ◽  
Vol 40 (4) ◽  
pp. 348-354 ◽  
Author(s):  
Fumiya Shinohara ◽  
Saya Arakaki ◽  
Taiju Amano ◽  
Masabumi Minami ◽  
Katsuyuki Kaneda
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Pyramidal Neurons

scholarly journals Maturation of Layer V Pyramidal Neurons in the Rat Prefrontal Cortex: Intrinsic Properties and Synaptic Function

2004 ◽  
Vol 91 (3) ◽  
pp. 1171-1182 ◽  
Author(s):  
Zhong-wei Zhang
Keyword(s):  
Prefrontal Cortex ◽  
Time Constant ◽  
Pyramidal Neurons ◽  
Rapid Development ◽  
Input Resistance ◽  
Synaptic Function ◽  
Resting Potential ◽  
Intrinsic Properties ◽  
Patch Clamp Recording ◽  
Layer V

Layer V pyramidal neurons in the rat medial prefrontal cortex (PFC) were examined with whole cell patch-clamp recording in acute slices from postnatal day 1 (P1) to P36. In the first few days after birth, layer V pyramidal neurons had low resting potentials, high-input resistance, and long membrane time constant. During the next 2 wk, the resting potential shifted by -14 mV, while the input resistance and time constant decreased by 15- and 4-fold, respectively. Between P3 and P21, the surface area of the cell body doubled, while the total lengths of apical and basal dendrites increased by 5- and 13-fold, respectively. Action potentials (APs) were observed at all aged tested. The peak amplitude of APs increased by 30 mV during the first 3 wk, while AP rise time and half-maximum duration shortened significantly. Compared with neurons at P21 or older, neurons in the first week required much smaller currents to reach their maximum firing frequencies, but the maximum frequencies were lower than those at older ages. Stimulation of layer II/III induced monosynaptic responses in neurons older than P5. Paired-pulse responses showed a short-term depression at P7, which shifted progressive to facilitation at older ages. These results demonstrate that, similar to other neurons in the brain, layer V pyramidal neurons in the PFC undergo a period of rapid development during the first 3 wk after birth. These findings suggest that the intrinsic properties of neurons and the properties of synaptic inputs develop concomitantly during early life.

Sign in / Sign up

Export Citation Format

Share Document