Prefrontal cortex, hippocampus, and basolateral amygdala plasticity in a rat model of autism spectrum

Synapse ◽  
2014 ◽  
Vol 68 (10) ◽  
pp. 468-473 ◽  
Author(s):  
Nuvia Sosa-Díaz ◽  
Maria Elena Bringas ◽  
Marco Atzori ◽  
Gonzalo Flores
Keyword(s):  
Prefrontal Cortex ◽  
Rat Model ◽  
Basolateral Amygdala ◽  
Autism Spectrum

scholarly journals Altered synaptic ultrastructure in the prefrontal cortex of Shank3-deficient rats

2020 ◽  
Author(s):  
Sarah Jacot-Descombes ◽  
Neha U Keshav ◽  
Dara L. Dickstein ◽  
Bridget Wicinski ◽  
William G. M. Janssen ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Rat Model ◽  
Postsynaptic Density ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Head Diameter ◽  
Density Area ◽  
Synaptic Ultrastructure

Abstract Background Deletion or mutations of SHANK3 lead to Phelan-McDermid syndrome and monogenic forms of autism spectrum disorder. SHANK3 encodes its eponymous scaffolding protein at excitatory glutamatergic synapses. Altered dendritic and spine morphology in the hippocampus, cerebellum and striatum have been associated with behavioral impairments in various Shank3-deficient animal models. Given the attentional deficit reported in these animals, our study explored whether deficiency of Shank3 in a rat model alters synaptic ultrastructure in the medial prefrontal cortex. Methods We used electron microscopy to determine the density of asymmetric synapses in layer III excitatory neurons of the medial prefrontal cortex in 5 week-old Shank3-homozygous knockout ( Shank3 -KO), heterozygous ( Shank3 -Het), and wild-type (WT) rats. We also measured postsynaptic density length, postsynaptic density area, and head diameter of dendritic spines at these synapses. Results All three groups had comparable synapse density and postsynaptic density length. Spine head diameter of Shank3 -Het rats, but not Shank3 -KO, was larger than WT rats. Shank3 -Het rats had wider head diameter in non-perforated synapses compared to WT and Shank3 -KO rats. The total postsynaptic density area was significantly larger in Shank3 -Het rats compared to Shank3 -KO and WT rats. These findings represent preliminary evidence for synaptic ultrastructural alterations in the medial prefrontal cortex of rats that lack one copy of Shank3 and mimic the heterozygous loss of SHANK3 in Phelan-McDermid syndrome. Limitations The Shank3 deletion in the rat model we used does not affect all isoforms of the protein and as such, would only model the effect of the mutations resulting in loss of the N-terminus of the protein. Given the higher prevalence of ASD in males, this study focused only on synaptic ultrastructure in male Shank3 -deficient rats. Conclusions We observed increased head diameter and postsynaptic density area in rats heterozygous for Shank3 deficiency. Further investigations of the mechanisms leading to altered synaptic ultrastructure in this animal model will enable us to understand better the role that Shank3 protein plays in autism spectrum disorder and Phelan-McDermid syndrome.

scholarly journals Altered synaptic ultrastructure in the prefrontal cortex of Shank3-deficient rats

2020 ◽  
Author(s):  
Sarah Jacot-Descombes ◽  
Neha U Keshav ◽  
Dara L. Dickstein ◽  
Bridget Wicinski ◽  
William G. M. Janssen ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Rat Model ◽  
Preliminary Evidence ◽  
Autism Spectrum ◽  
Dendritic Morphology ◽  
Scaffolding Protein ◽  
Spine Density ◽  
Synaptic Structure ◽  
Synaptic Ultrastructure ◽  
Behavioral Impairments

Abstract Background Deletion or mutations of SHANK3 lead to Phelan-McDermid syndrome and monogenic forms of autism spectrum disorder (ASD). SHANK3 encodes its eponymous scaffolding protein at excitatory glutamatergic synapses. Altered morphology of dendrites and spines in the hippocampus, cerebellum, and striatum have been associated with behavioral impairments in Shank3-deficient animal models. Given the attentional deficit in these animals, our study explored whether deficiency of Shank3 in a rat model alters neuron morphology and synaptic ultrastructure in the medial prefrontal cortex (mPFC). Methods We assessed dendrite and spine morphology and spine density in mPFC layer III neurons in Shank3 -homozygous knockout ( Shank3 -KO), heterozygous ( Shank3 -Het), and wild-type (WT) rats. We used electron microscopy to determine the density of asymmetric synapses in mPFC layer III excitatory neurons in these rats. We measured postsynaptic density (PSD) length, PSD area, and head diameter (HD) of spines at these synapses. Results Basal dendritic morphology was similar among the three genotypes. Spine density and morphology were comparable, but more thin and mushroom spines had larger head volumes in Shank3 -Het compared to WT and Shank3 -KO. All three groups had comparable synapse density and PSD length. Spine HD of total and non-perforated synapses in Shank3 -Het rats, but not Shank3 -KO rats, was significantly larger than in WT rats. The total and non-perforated PSD area was significantly larger in Shank3 -Het rats compared to Shank3 -KO rats. These findings represent preliminary evidence for synaptic ultrastructural alterations in the mPFC of rats that lack one copy of Shank3 and mimic the heterozygous loss of SHANK3 in Phelan-McDermid syndrome. Limitations The Shank3 deletion in the rat model we used does not affect all isoforms of the protein and would only model the effect of the mutations resulting in loss of the N-terminus of the protein. Given the higher prevalence of ASD in males, the ultrastructural study focused only on synaptic structure in male Shank3 -deficient rats. Conclusions We observed increased HD and PSD area in Shank3 -Het rats. These observations suggest the occurrence of altered synaptic ultrastructure in this animal model, further pointing to a key role of defective expression of the Shank3 protein in ASD and Phelan-McDermid syndrome.

scholarly journals Altered synaptic ultrastructure in the prefrontal cortex of Shank3-deficient rats

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Sarah Jacot-Descombes ◽  
Neha U. Keshav ◽  
Dara L. Dickstein ◽  
Bridget Wicinski ◽  
William G. M. Janssen ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Rat Model ◽  
Preliminary Evidence ◽  
Autism Spectrum ◽  
Dendritic Morphology ◽  
Scaffolding Protein ◽  
Spine Density ◽  
Synaptic Structure ◽  
Synaptic Ultrastructure ◽  
Behavioral Impairments

Abstract Background Deletion or mutations of SHANK3 lead to Phelan–McDermid syndrome and monogenic forms of autism spectrum disorder (ASD). SHANK3 encodes its eponymous scaffolding protein at excitatory glutamatergic synapses. Altered morphology of dendrites and spines in the hippocampus, cerebellum, and striatum have been associated with behavioral impairments in Shank3-deficient animal models. Given the attentional deficit in these animals, our study explored whether deficiency of Shank3 in a rat model alters neuron morphology and synaptic ultrastructure in the medial prefrontal cortex (mPFC). Methods We assessed dendrite and spine morphology and spine density in mPFC layer III neurons in Shank3-homozygous knockout (Shank3-KO), heterozygous (Shank3-Het), and wild-type (WT) rats. We used electron microscopy to determine the density of asymmetric synapses in mPFC layer III excitatory neurons in these rats. We measured postsynaptic density (PSD) length, PSD area, and head diameter (HD) of spines at these synapses. Results Basal dendritic morphology was similar among the three genotypes. Spine density and morphology were comparable, but more thin and mushroom spines had larger head volumes in Shank3-Het compared to WT and Shank3-KO. All three groups had comparable synapse density and PSD length. Spine HD of total and non-perforated synapses in Shank3-Het rats, but not Shank3-KO rats, was significantly larger than in WT rats. The total and non-perforated PSD area was significantly larger in Shank3-Het rats compared to Shank3-KO rats. These findings represent preliminary evidence for synaptic ultrastructural alterations in the mPFC of rats that lack one copy of Shank3 and mimic the heterozygous loss of SHANK3 in Phelan–McDermid syndrome. Limitations The Shank3 deletion in the rat model we used does not affect all isoforms of the protein and would only model the effect of mutations resulting in loss of the N-terminus of the protein. Given the higher prevalence of ASD in males, the ultrastructural study focused only on synaptic structure in male Shank3-deficient rats. Conclusions We observed increased HD and PSD area in Shank3-Het rats. These observations suggest the occurrence of altered synaptic ultrastructure in this animal model, further pointing to a key role of defective expression of the Shank3 protein in ASD and Phelan–McDermid syndrome.

025 Sleep Disruption on an Orbital Shaker alters Glutamate in Prairie Vole Prefrontal Cortex

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A11-A12
Author(s):  
Carolyn Jones ◽  
Randall Olson ◽  
Alex Chau ◽  
Peyton Wickham ◽  
Ryan Leriche ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Prefrontal Cortex ◽  
Early Life ◽  
Autism Spectrum ◽  
Prairie Vole ◽  
Sleep Disruption ◽  
Glutamatergic Synapses ◽  
The Brain ◽  
Orbital Shaker

Abstract Introduction Glutamate concentrations in the cortex fluctuate with the sleep wake cycle in both rodents and humans. Altered glutamatergic signaling, as well as the early life onset of sleep disturbances have been implicated in neurodevelopmental disorders such as autism spectrum disorder. In order to study how sleep modulates glutamate activity in brain regions relevant to social behavior and development, we disrupted sleep in the socially monogamous prairie vole (Microtus ochrogaster) rodent species and quantified markers of glutamate neurotransmission within the prefrontal cortex, an area of the brain responsible for advanced cognition and complex social behaviors. Methods Male and female prairie voles were sleep disrupted using an orbital shaker to deliver automated gentle cage agitation at continuous intervals. Sleep was measured using EEG/EMG signals and paired with real time glutamate concentrations in the prefrontal cortex using an amperometric glutamate biosensor. This same method of sleep disruption was applied early in development (postnatal days 14–21) and the long term effects on brain development were quantified by examining glutamatergic synapses in adulthood. Results Consistent with previous research in rats, glutamate concentration in the prefrontal cortex increased during periods of wake in the prairie vole. Sleep disruption using the orbital shaker method resulted in brief cortical arousals and reduced time in REM sleep. When applied during development, early life sleep disruption resulted in long-term changes in both pre- and post-synaptic components of glutamatergic synapses in the prairie vole prefrontal cortex including increased density of immature spines. Conclusion In the prairie vole rodent model, sleep disruption on an orbital shaker produces a sleep, behavioral, and neurological phenotype that mirrors aspects of autism spectrum disorder including altered features of excitatory neurotransmission within the prefrontal cortex. Studies using this method of sleep disruption combined with real time biosensors for excitatory neurotransmitters will enhance our understanding of modifiable risk factors, such as sleep, that contribute to the altered development of glutamatergic synapses in the brain and their relationship to social behavior. Support (if any) NSF #1926818, VA CDA #IK2 BX002712, Portland VA Research Foundation, NIH NHLBI 5T32HL083808-10, VA Merit Review #I01BX001643

The Role of the Medial Prefrontal Cortex in Moderating Neural Representations of Self and Other in Primates

2021 ◽  
Vol 44 (1) ◽  
Author(s):  
Masaki Isoda
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Critical Role ◽  
Autism Spectrum ◽  
Annual Review ◽  
Publication Date ◽  
Self And Other ◽  
Neural Representations ◽  
The Social

As a frontal node in the primate social brain, the medial prefrontal cortex (MPFC) plays a critical role in coordinating one's own behavior with respect to that of others. Current literature demonstrates that single neurons in the MPFC encode behavior-related variables such as intentions, actions, and rewards, specifically for self and other, and that the MPFC comes into play when reflecting upon oneself and others. The social moderator account of MPFC function can explain maladaptive social cognition in people with autism spectrum disorder, which tips the balance in favor of self-centered perspectives rather than taking into consideration the perspective of others. Several strands of evidence suggest a hypothesis that the MPFC represents different other mental models, depending on the context at hand, to better predict others’ emotions and behaviors. This hypothesis also accounts for aberrant MPFC activity in autistic individuals while they are mentalizing others. Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

A metabolomics-based approach for ranking the depressive level in a chronic unpredictable mild stress rat model

RSC Advances ◽  
2016 ◽  
Vol 6 (31) ◽  
pp. 25751-25765 ◽  
Author(s):  
Xinyu Yu ◽  
Shanlei Qiao ◽  
Di Wang ◽  
Jiayong Dai ◽  
Jun Wang ◽  
...  
Keyword(s):  
Animal Model ◽  
Major Depressive Disorder ◽  
Prefrontal Cortex ◽  
Depressive Disorder ◽  
Rat Model ◽  
Untargeted Metabolomics ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Major Depressive ◽  
Metabolomics Study

An untargeted metabolomics study to investigate the metabolome change in plasma, hippocampus and prefrontal cortex (PFC) in an animal model with a major depressive disorder (MDD) had been conducted.

scholarly journals Transcranial Direct Current Stimulation (tDCS) over the Left Dorsal Lateral Prefrontal Cortex in Children with Autism Spectrum Disorder (ASD)

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jiujun Qiu ◽  
Xuejun Kong ◽  
Jihan Li ◽  
Jie Yang ◽  
Yiting Huang ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Prefrontal Cortex ◽  
Direct Current ◽  
Transcranial Direct Current Stimulation ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Sleep Habits ◽  
Lateral Prefrontal Cortex ◽  
Direct Current Stimulation ◽  
Children With Asd

Recently, transcranial direct current stimulation (tDCS) has been applied to relieve symptoms in individuals with autism spectrum disorder (ASD). In this prospective, parallel, single-blinded, randomized study, we investigate the modulation effect of three-week tDCS treatment at the left dorsal lateral prefrontal cortex (DLPFC) in children with ASD. 47 children with ASD were enrolled, and 40 (20 in each group) completed the study. The primary outcomes are Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), and the Repetitive Behavior Scale-Revised (RBS-R). We found that children with ASD can tolerate three-week tDCS treatment with no serious adverse events detected. A within-group comparison showed that real tDCS, but not sham tDCS, can significantly reduce the scores of CARS, Children’s Sleep Habits Questionnaire (CSHQ), and general impressions in CARS (15th item). Real tDCS produced significant score reduction in the CSHQ and in CARS general impressions when compared to the effects of sham tDCS. The pilot study suggests that three-week left DLPFC tDCS is well-tolerated and may hold potential in relieving some symptoms in children with ASD.

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