The Prefrontal Cortex Makes the Brain a Preadaptive System

The aim of the study was to evaluate the rate of polymerization of tubulin into microtubules and determine the level of colchicine binding (colchicine-binding activity of tubulin) in the prefrontal cortex in schizophrenia, vascular dementia (VD) and control. Colchicine-binding activity of tubulin was determined by Sherlinе in tubulin-enriched extracts of proteins from the samples. Measurement of light scattering during the polymerization of the tubulin was carried out using the nephelometric method at a wavelength of 450-550 nm. There was a significant decrease in colchicine-binding activity and the rate of tubulin polymerization in the prefrontal cortex in both diseases, and in VD to a greater extent than in schizophrenia. The obtained results suggest that not only in Alzheimer's disease, but also in other mental diseases such as schizophrenia and VD, there is a decrease in the level of tubulin in the prefrontal cortex of the brain, although to a lesser extent than in Alzheimer's disease, and consequently the amount of microtubules.

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Activation of Melanocortin-4 Receptor by a Synthetic Agonist Inhibits Ethanolinduced Neuroinflammation in Rats

Current Pharmaceutical Design ◽

10.2174/1381612825666191216145153 ◽

2020 ◽

Vol 25 (45) ◽

pp. 4799-4805 ◽

Cited By ~ 3

Author(s):

Osvaldo Flores-Bastías ◽

Gonzalo I. Gómez ◽

Juan A. Orellana ◽

Eduardo Karahanian

Keyword(s):

Prefrontal Cortex ◽

Alcohol Consumption ◽

Ethanol Intake ◽

Neuroinflammatory Response ◽

Agonist Peptide ◽

Melanocortin 4 Receptor ◽

Tnf Α ◽

Cord Injury ◽

High Ethanol ◽

The Brain

Background: High ethanol intake induces a neuroinflammatory response resulting in the subsequent maintenance of chronic alcohol consumption. The melanocortin system plays a pivotal role in the modulation of alcohol consumption. Interestingly, it has been shown that the activation of melanocortin-4 receptor (MC4R) in the brain decreases the neuroinflammatory response in models of brain damage other than alcohol consumption, such as LPS-induced neuroinflammation, cerebral ischemia, glutamate excitotoxicity, and spinal cord injury. Objectives: In this work, we aimed to study whether MC4R activation by a synthetic MC4R-agonist peptide prevents ethanol-induced neuroinflammation, and if alcohol consumption produces changes in MC4R expression in the hippocampus and hypothalamus. Methods: Ethanol-preferring Sprague Dawley rats were selected offering access to 20% ethanol on alternate days for 4 weeks (intermittent access protocol). After this time, animals were i.p. administered an MC4R agonist peptide in the last 2 days of the protocol. Then, the expression of the proinflammatory cytokines interleukin 6 (IL-6), interleukin 1-beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) were measured in the hippocampus, hypothalamus and prefrontal cortex. It was also evaluated if ethanol intake produces alterations in the expression of MC4R in the hippocampus and the hypothalamus. Results: Alcohol consumption increased the expression of MC4R in the hippocampus and the hypothalamus. The administration of the MC4R agonist reduced IL-6, IL-1β and TNF-α levels in hippocampus, hypothalamus and prefrontal cortex, to those observed in control rats that did not drink alcohol. Conclusion: High ethanol consumption produces an increase in the expression of MC4R in the hippocampus and hypothalamus. The administration of a synthetic MC4R-agonist peptide prevents neuroinflammation induced by alcohol consumption in the hippocampus, hypothalamus, and prefrontal cortex. These results could explain the effect of α-MSH and other synthetic MC4R agonists in decreasing alcohol intake through the reduction of the ethanol-induced inflammatory response in the brain.

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

SLEEP ◽

10.1093/sleep/zsab072.024 ◽

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

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Glia Not Neurons: Uncovering Brain Dysmaturation in a Rat Model of Alzheimer’s Disease

Biomedicines ◽

10.3390/biomedicines9070823 ◽

2021 ◽

Vol 9 (7) ◽

pp. 823

Author(s):

Ekaterina A. Rudnitskaya ◽

Tatiana A. Kozlova ◽

Alena O. Burnyasheva ◽

Natalia A. Stefanova ◽

Nataliya G. Kolosova

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Prefrontal Cortex ◽

Brain Structures ◽

Time Frame ◽

Oxys Rats ◽

Unknown Etiology ◽

Suitable Model ◽

Model Of Alzheimer’S Disease ◽

The Brain

Sporadic Alzheimer’s disease (AD) is a severe disorder of unknown etiology with no definite time frame of onset. Recent studies suggest that middle age is a critical period for the relevant pathological processes of AD. Nonetheless, sufficient data have accumulated supporting the hypothesis of “neurodevelopmental origin of neurodegenerative disorders”: prerequisites for neurodegeneration may occur during early brain development. Therefore, we investigated the development of the most AD-affected brain structures (hippocampus and prefrontal cortex) using an immunohistochemical approach in senescence-accelerated OXYS rats, which are considered a suitable model of the most common—sporadic—type of AD. We noticed an additional peak of neurogenesis, which coincides in time with the peak of apoptosis in the hippocampus of OXYS rats on postnatal day three. Besides, we showed signs of delayed migration of neurons to the prefrontal cortex as well as disturbances in astrocytic and microglial support of the hippocampus and prefrontal cortex during the first postnatal week. Altogether, our results point to dysmaturation during early development of the brain—especially insufficient glial support—as a possible “first hit” leading to neurodegenerative processes and AD pathology manifestation later in life.

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Cannabidiol Has a Unique Effect on Global Brain Activity: A Pharmacological, Functional MRI Study in Awake Mice

10.21203/rs.3.rs-253550/v1 ◽

2021 ◽

Author(s):

Aymen Sadaka ◽

Ana Ozuna ◽

Richard Ortiz ◽

Praveen Kulkarni ◽

Clare Johnson ◽

...

Keyword(s):

Prefrontal Cortex ◽

Brain Activity ◽

Stress Disorders ◽

Functional Coupling ◽

Specific Information ◽

Imaging Data ◽

Post Traumatic Stress ◽

Brain Areas ◽

Dose Dependent ◽

The Brain

Abstract Background: The phytocannabinoid cannabidiol (CBD) is a potential treatment for post-traumatic stress disorders. How does CBD interact with the brain to alter behavior? We hypothesized that CBD would produce a dose-dependent reduction in brain activity and functional coupling in neural circuitry associated with fear and defense. Methods: During the scanning session awake mice were given vehicle or CBD (3, 10, or 30 mg/kg I.P.) and imaged for 10 min post treatment. Mice were also treated with the 10 mg/kg dose of CBD and imaged one hr later for resting state BOLD functional connectivity (rsFC). Imaging data were registered to a 3D MRI mouse atlas providing site-specific information on 138 different brain areas. Blood samples were collected for CBD measurements.Results: CBD produced a dose-dependent polarization of activation along the rostral-caudal axis of the brain. The olfactory bulb and prefrontal cortex showed an increase in positive BOLD whereas the brainstem and cerebellum showed a decrease in BOLD signal. This negative BOLD affected many areas connected to the ascending reticular activating system (ARAS). The ARAS was decoupled to much of the brain but was hyperconnected to the olfactory system and prefrontal cortex. The pattern of ARAS connectivity closely overlapped with brain areas showing high levels N-acyl-phosphatidylethanolamines-specific phospholipase D (NAPE-PLD) messenger RNA.Conclusion: The CBD-induced decrease in ARAS activity is consistent with an emerging literature suggesting that CBD reduces autonomic arousal under conditions of emotional and physical stress. The putative target and mechanism of action is NAPE-PLD the enzyme responsible for the biosynthesis of lipid signaling molecules like anandamide.

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Cultural variation in the gray matter volume of the prefrontal cortex is moderated by the dopamine D4 receptor gene (DRD4)

Cerebral Cortex ◽

10.1093/cercor/bhy271 ◽

2018 ◽

Vol 29 (9) ◽

pp. 3922-3931 ◽

Cited By ~ 9

Author(s):

Qinggang Yu ◽

Nobuhito Abe ◽

Anthony King ◽

Carolyn Yoon ◽

Israel Liberzon ◽

...

Keyword(s):

Prefrontal Cortex ◽

Orbitofrontal Cortex ◽

Receptor Gene ◽

Cultural Influences ◽

Dopamine D4 Receptor ◽

East Asians ◽

European Americans ◽

The Difference ◽

D4 Receptor ◽

The Brain

Abstract Recent evidence suggests a systematic cultural difference in the volume/thickness of prefrontal regions of the brain. However, origins of this difference remain unclear. Here, we addressed this gap by adopting a unique genetic approach. People who carry the 7- or 2-repeat (7/2-R) allele of the dopamine D4 receptor gene (DRD4) are more sensitive to environmental influences, including cultural influences. Therefore, if the difference in brain structure is due to cultural influences, it should be moderated by DRD4. We recruited 132 young adults (both European Americans and Asian-born East Asians). Voxel-based morphometry showed that gray matter (GM) volume of the medial prefrontal cortex and the orbitofrontal cortex was significantly greater among European Americans than among East Asians. Moreover, the difference in GM volume was significantly more pronounced among carriers of the 7/2-R allele of DRD4 than among non-carriers. This pattern was robust in an alternative measure assessing cortical thickness. A further exploratory analysis showed that among East Asian carriers, the number of years spent in the U.S. predicted increased GM volume in the orbitofrontal cortex. The present evidence is consistent with a view that culture shapes the brain by mobilizing epigenetic pathways that are gradually established through socialization and enculturation.

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Subjective value and decision entropy are jointly encoded by aligned gradients across the human brain

10.1101/2020.02.18.954362 ◽

2020 ◽

Author(s):

Sebastian Bobadilla-Suarez ◽

Olivia Guest ◽

Bradley C. Love

Keyword(s):

Prefrontal Cortex ◽

Human Brain ◽

Ventromedial Prefrontal Cortex ◽

Neural Representation ◽

Retrospective Evaluation ◽

Systematic Fashion ◽

Subjective Value ◽

Fmri Analysis ◽

The Relationship ◽

The Brain

AbstractRecent work has considered the relationship between value and confidence in both behavior and neural representation. Here we evaluated whether the brain organizes value and confidence signals in a systematic fashion that reflects the overall desirability of options. If so, regions that respond to either increases or decreases in both value and confidence should be widespread. We strongly confirmed these predictions through a model-based fMRI analysis of a mixed gambles task that assessed subjective value (SV) and inverse decision entropy (iDE), which is related to confidence. Purported value areas more strongly signalled iDE than SV, underscoring how intertwined value and confidence are. A gradient tied to the desirability of actions transitioned from positive SV and iDE in ventromedial prefrontal cortex to negative SV and iDE in dorsal medial prefrontal cortex. This alignment of SV and iDE signals could support retrospective evaluation to guide learning and subsequent decisions.

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Task dependence of neural representations of global scene properties but not scene categories in the prefrontal cortex

10.1101/2020.12.04.412445 ◽

2020 ◽

Author(s):

Yaelan Jung ◽

Dirk B. Walther

Keyword(s):

Prefrontal Cortex ◽

Visual Cortex ◽

Scene Perception ◽

Sound Level ◽

Task Context ◽

Complex Scene ◽

Neural Representations ◽

Task Conditions ◽

Scene Content ◽

The Brain

AbstractNatural scenes deliver rich sensory information about the world. Decades of research has shown that the scene-selective network in the visual cortex represents various aspects of scenes. It is, however, unknown how such complex scene information is processed beyond the visual cortex, such as in the prefrontal cortex. It is also unknown how task context impacts the process of scene perception, modulating which scene content is represented in the brain. In this study, we investigate these questions using scene images from four natural scene categories, which also depict two types of global scene properties, temperature (warm or cold), and sound-level (noisy or quiet). A group of healthy human subjects from both sexes participated in the present study using fMRI. In the study, participants viewed scene images under two different task conditions; temperature judgment and sound-level judgment. We analyzed how different scene attributes (scene categories, temperature, and sound-level information) are represented across the brain under these task conditions. Our findings show that global scene properties are only represented in the brain, especially in the prefrontal cortex, when they are task-relevant. However, scene categories are represented in the brain, in both the parahippocampal place area and the prefrontal cortex, regardless of task context. These findings suggest that the prefrontal cortex selectively represents scene content according to task demands, but this task selectivity depends on the types of scene content; task modulates neural representations of global scene properties but not of scene categories.

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Neuronal Correlates of Multiple Top–Down Signals during Covert Tracking of Moving Objects in Macaque Prefrontal Cortex

Journal of Cognitive Neuroscience ◽

10.1162/jocn_a_00265 ◽

2012 ◽

Vol 24 (10) ◽

pp. 2043-2056 ◽

Cited By ~ 6

Author(s):

Ayano Matsushima ◽

Masaki Tanaka

Keyword(s):

Prefrontal Cortex ◽

Object Tracking ◽

Visual Processing ◽

Moving Objects ◽

Top Down ◽

Selective Suppression ◽

Internal Object ◽

Object Segregation ◽

Task Irrelevant ◽

The Brain

Resistance to distraction is a key component of executive functions and is strongly linked to the prefrontal cortex. Recent evidence suggests that neural mechanisms exist for selective suppression of task-irrelevant information. However, neuronal signals related to selective suppression have not yet been identified, whereas nonselective surround suppression, which results from attentional enhancement for relevant stimuli, has been well documented. This study examined single neuron activities in the lateral PFC when monkeys covertly tracked one of randomly moving objects. Although many neurons responded to the target, we also found a group of neurons that exhibited a selective response to the distractor that was visually identical to the target. Because most neurons were insensitive to an additional distractor that explicitly differed in color from the target, the brain seemed to monitor the distractor only when necessary to maintain internal object segregation. Our results suggest that the lateral PFC might provide at least two top–down signals during covert object tracking: one for enhancement of visual processing for the target and the other for selective suppression of visual processing for the distractor. These signals might work together to discriminate objects, thereby regulating both the sensitivity and specificity of target choice during covert object tracking.

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Mitochondrial respiratory chain activity in an animal model of mania induced by ouabain

Acta Neuropsychiatrica ◽

10.1111/j.1601-5215.2011.00543.x ◽

2011 ◽

Vol 23 (3) ◽

pp. 106-111 ◽

Cited By ~ 2

Author(s):

Tiago P. Freitas ◽

Gislaine T. Rezin ◽

Daiane B. Fraga ◽

Morgana Moretti ◽

Julia S. Vieira ◽

...

Keyword(s):

Animal Model ◽

Prefrontal Cortex ◽

Respiratory Chain ◽

Rebound Effect ◽

Mitochondrial Respiratory Chain ◽

Face Validity ◽

Mitochondrial Respiratory Chain Activity ◽

Respiratory Chain Activity ◽

The Brain ◽

Mitochondrial Respiratory

Objectives: Bipolar disorder (BD) is a mental illness associated with higher rates of suicide. The present study aims to investigate the brain mitochondrial respiratory chain activity in an animal model of mania induced by ouabain.Methods: Adult male Wistar rats received a single intracerebroventricular administration of ouabain (10−3 and 10−2 M) or vehicle. Locomotor activity was measured using the open field test. Mitochondrial respiratory chain activity was measured in the brain of rats 1 h and 7 days after ouabain administration.Results: Our results showed that spontaneous locomotion was increased 1 h and 7 days after ouabain administration. Complexes I, III and IV activities were increased in the prefrontal cortex, hippocampus and striatum immediately after the administration of ouabain, at the concentration of 10−3 and 10−2 M. Moreover, complex II activity was increased only in the prefrontal cortex at the concentration of 10−2 M. On the other hand, no significant alterations were observed in complex I activity 7 days after ouabain administration. However, an increase in complexes II, III and IV activities was observed only in the prefrontal cortex at the concentration of 10−2 M.Conclusion: Our findings suggest an increase in the activities of mitochondrial respiratory chain in this model of mania. A possible explanation is that these findings occur as a rebound effect trying to compensate for a decrease of ATP deprivation in BD. The present findings suggest that this model may present good face validity and a limitation in construct validity.

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