scholarly journals Muscarinic receptors regulate auditory and prefrontal cortical communication during auditory processing

2018 ◽  
Author(s):  
Nicholas M. James ◽  
Howard J. Gritton ◽  
Nancy Kopell ◽  
Kamal Sen ◽  
Xue Han
Keyword(s):  
Muscarinic Receptors ◽  
Auditory Processing ◽  
Sensory Response ◽  
Cholinergic Antagonists ◽  
List Type ◽  
Behavioral Experiments ◽  
Cortical Function ◽  
Cortical Dynamics ◽  
Prefrontal Cortical ◽  
Cholinergic Signaling

AbstractMuch of our understanding about how acetylcholine modulates prefrontal cortical (PFC) networks comes from behavioral experiments that examine cortical dynamics during highly attentive states. However, much less is known about how PFC is recruited during passive sensory processing and how acetylcholine may regulate connectivity between cortical areas outside of task performance. To investigate the involvement of PFC and cholinergic neuromodulation in passive auditory processing, we performed simultaneous recordings in the auditory cortex (AC) and PFC in awake head fixed mice presented with a white noise auditory stimulus in the presence or absence of local cholinergic antagonists in AC. We found that a subset of PFC neurons were strongly driven by auditory stimuli even when the stimulus had no associative meaning, suggesting PFC monitors stimuli under passive conditions. We also found that cholinergic signaling in AC shapes the strength of auditory driven response in PFC, by modulating the intra-cortical sensory response through muscarinic interactions in AC. Taken together, these findings provide novel evidence that cholinergic mechanisms have a continuous role in cortical gating through muscarinic receptors during passive processing and expand traditional views of prefrontal cortical function and the contributions of cholinergic modulation in sensory gating.HighlightsPrefrontal cortex actively monitors non-associative stimuli under passive conditionsAcetylcholine facilitates cortical signaling even outside of attentional contextsLocal scopolamine infusion reduced intracortical signaling and impaired cortical gatingmAChR have an ongoing role in sound processing

scholarly journals Muscarinic receptors regulate auditory and prefrontal cortical communication during auditory processing

2019 ◽  
Vol 144 ◽  
pp. 155-171 ◽  
Author(s):  
Nicholas M. James ◽  
Howard J. Gritton ◽  
Nancy Kopell ◽  
Kamal Sen ◽  
Xue Han
Keyword(s):  
Muscarinic Receptors ◽  
Auditory Processing ◽  
Prefrontal Cortical

Effects of the DAT 3’UTR VNTR Genotype on Brain Function in Healthy Subjects and Patients with Schizophrenia

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
D.P. Prata ◽  
A. Mechelli ◽  
C. Fu ◽  
M. Picchioni ◽  
F. Kane ◽  
...  
Keyword(s):  
Verbal Fluency ◽  
Diagnostic Group ◽  
Cortical Activation ◽  
Anterior Cingulate ◽  
List Type ◽  
Type Number ◽  
Cortical Function ◽  
Repeat Allele ◽  
Word Generation ◽  
Brain Responses

Aims:To examine the effect of a polymorphism in the Dopamine Transporter (DAT) gene on brain activation during executive function and, for the first time:1.determine the extent to which this is altered in schizophrenia and2.use a verbal fluency paradigm.This is relevant since:1.DAT plays a key role in the regulation of dopamine, which modulates cortical activation during cognitive tasks and2.a disruption of dopamine function is a fundamental pathophysiological feature of schizophrenia.Method:Functional magnetic resonance imaging was used to measure whole-brain responses during overt verbal fluency in 85 subjects: 44 healthy volunteers and 41 DSM-IV schizophrenia patients. Main effects of genotype and diagnostic group on activation and their interaction were estimated using an ANOVA in SPM5.Results:The 10-repeat allele of the 3'UTR VNTR was associated with greater activation than the 9-repeat allele in the left (Z=4.8; FWEp=0.005) and right (Z=4.2; FWEp=0.057) anterior insula and with decreased activation in the rostral anterior cingulate (Z=4.3 FWEp=0.04) during word generation (versus baseline). These effects were irrespective of diagnostic group but generally more marked in patients. There were also strong trends for groupxgenotype interactions in the left middle frontal gyrus and the left nucleus accumbens. Analysis was controlled for task performance, IQ, antipsychotic medication, psychopathology and demographics.Conclusion:Cortical function during executive tasks is normally modulated by variation in the DAT gene, effect which is dependent on the brain region. DAT's effect may be altered in schizophrenia patients, which may reflect altered central dopamine function.

scholarly journals Development of the MAM model of schizophrenia in mice: Sex similarities and differences of hippocampal and prefrontal cortical function

2019 ◽  
Vol 144 ◽  
pp. 193-207 ◽  
Author(s):  
Kleanthi Chalkiadaki ◽  
Aggeliki Velli ◽  
Evangelos Kyriazidis ◽  
Vasiliki Stavroulaki ◽  
Vasilis Vouvoutsis ◽  
...  
Keyword(s):  
Cortical Function ◽  
Prefrontal Cortical ◽  
Similarities And Differences

Social vulnerability and prefrontal cortical function in elderly people: a report from the Canadian Study of Health and Aging

2010 ◽  
Vol 23 (3) ◽  
pp. 450-458 ◽  
Author(s):  
Melissa K. Andrew ◽  
John D. Fisk ◽  
Kenneth Rockwood
Keyword(s):  
Social Vulnerability ◽  
Verbal Fluency ◽  
Mmse Score ◽  
Vulnerable Group ◽  
Cortical Function ◽  
Impaired Performance ◽  
Wechsler Memory Scale ◽  
Prefrontal Cortical ◽  
Token Test ◽  
Psychoactive Medications

ABSTRACTBackground:Prefrontal cortical lobe function is related to social behavior in humans. We investigated whether performance on tests of prefrontal cortical function was associated with social vulnerability. Associations with non-frontal cognitive function were investigated for comparison.Methods:1216 participants aged 70+ of the Canadian Study of Health and Aging-2 screening examination, who also underwent detailed neuropsychological testing, comprised the study sample. Performance on WAIS-R abstraction, WAIS-R comprehension, Trails B, FAS and category verbal fluency, Block construction, Token Test and Wechsler Memory Scale Information Subset was tested in relation to the participant's level of social vulnerability using regression models adjusted for age, education, sex, frailty, MMSE score, diagnosis of depression, and use of psychoactive medications. Social vulnerability was measured by an index comprising many social problems or “deficits”.Results:The most socially vulnerable group had worse performance on FAS verbal fluency, generating 4.1 fewer words (95% CI: 1.8–6.4, p<0.001) than those in the least socially vulnerable group; those with intermediate social vulnerability generated 2.6 fewer words (95% CI: 0.4–4.8, p = 0.02). Social vulnerability was also associated, though less strongly, with category verbal fluency. The most socially vulnerable people had impaired performance on the Trails B, taking 37 seconds longer (95% CI: 11–63, p = 0.005). These results were independent of age, education, sex, frailty, MMSE score, depression, and psychoactive medications. Social vulnerability was not associated with performance on WAIS-R abstraction, WAIS-R comprehension, Block Design, Token Test or Wechsler Memory Scale testsConclusions:High social vulnerability was associated with impaired performance on verbal fluency and set shifting but not with common sense judgment, abstraction, long-term memory, constructional ability, or language comprehension. The association between social functioning and the cognitive functions subserved by prefrontal cortex warrants further study.

Dysregulated Prefrontal Cortical RhoA Signal Transduction in Bipolar Disorder with Psychosis: New Implications for Disease Pathophysiology

2019 ◽  
Vol 30 (1) ◽  
pp. 59-71
Author(s):  
Bailey A Kermath ◽  
Amanda M Vanderplow ◽  
Michael E Cahill
Keyword(s):  
Signal Transduction ◽  
Bipolar Disorder ◽  
Signal Transduction Pathway ◽  
Signal Transduction Pathways ◽  
Cellular Functions ◽  
Protein Activity ◽  
Cortical Function ◽  
Prefrontal Cortical ◽  
Dorsolateral Prefrontal ◽  
Key Factor

Abstract While research has identified alterations in dorsolateral prefrontal cortical function as a key factor to the etiology of bipolar disorder, few studies have uncovered robust changes in protein signal transduction pathways in this disorder. Given the direct relevance of protein-based expressional alterations to cellular functions and because many of the key regulatory mechanisms for the disease pathogenesis likely include alterations in protein activity rather than changes in expression alone, the identification of alterations in discrete signal transduction pathways in bipolar disorder would have broad implications for understanding the disease pathophysiology. As prior microarray data point to a previously unrecognized involvement of the RhoA network in bipolar disorder, here we investigate the protein expression and activity of key components of a RhoA signal transduction pathway in dorsolateral prefrontal cortical homogenates from subjects with bipolar disorder. The results of this investigation implicate overactivation of prefrontal cortical RhoA signaling in specific subtypes of bipolar disorder. The specificity of these findings is demonstrated by a lack of comparable changes in schizophrenia; however, our findings do identify convergence between both disorders at the level of activity-mediated actin cytoskeletal regulation. These findings have implications for understanding the altered cortical synaptic connectivity of bipolar disorder.

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