The role of some brain structures in the switching of the descending influences in operantly conditioned rats

Ample evidence suggests that estrogens have strong influences on the occurrence of stress-related mood disorders, but the underlying mechanisms remain poorly understood. Through multiple approaches, we demonstrate that the G protein-coupled estrogen receptor (GPER) is widely distributed along the HPA axis and in brain structures critically involved in mood control. Genetic ablation of GPER in the rat resulted in significantly lower basal serum corticosterone level but enhanced ACTH release in response to acute restraint stress, especially in the female. GPER-/- rats of either sex displayed increased anxiety-like behaviors and deficits in learning and memory. Additionally, GPER deficiency led to aggravation of anxiety-like behaviors following single-prolonged stress (SPS). SPS caused significant decreases in serum corticosterone in WT but not in GPER-deficient rats. The results highlight an important role of GPER at multiple sites in regulation of the HPA axis and mood.

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Early oxygen levels contribute to brain injury in extremely preterm infants

Pediatric Research ◽

10.1038/s41390-021-01460-3 ◽

2021 ◽

Author(s):

Krista Rantakari ◽

Olli-Pekka Rinta-Koski ◽

Marjo Metsäranta ◽

Jaakko Hollmén ◽

Simo Särkkä ◽

...

Keyword(s):

Preterm Infants ◽

Brain Structures ◽

High Oxygen ◽

List Type ◽

Neurodevelopmental Outcomes ◽

Oxygen Levels ◽

Arterial Blood ◽

Extremely Preterm ◽

Extremely Preterm Infants

Abstract Background Extremely low gestational age newborns (ELGANs) are at risk of neurodevelopmental impairments that may originate in early NICU care. We hypothesized that early oxygen saturations (SpO2), arterial pO2 levels, and supplemental oxygen (FiO2) would associate with later neuroanatomic changes. Methods SpO2, arterial blood gases, and FiO2 from 73 ELGANs (GA 26.4 ± 1.2; BW 867 ± 179 g) during the first 3 postnatal days were correlated with later white matter injury (WM, MRI, n = 69), secondary cortical somatosensory processing in magnetoencephalography (MEG-SII, n = 39), Hempel neurological examination (n = 66), and developmental quotients of Griffiths Mental Developmental Scales (GMDS, n = 58). Results The ELGANs with later WM abnormalities exhibited lower SpO2 and pO2 levels, and higher FiO2 need during the first 3 days than those with normal WM. They also had higher pCO2 values. The infants with abnormal MEG-SII showed opposite findings, i.e., displayed higher SpO2 and pO2 levels and lower FiO2 need, than those with better outcomes. Severe WM changes and abnormal MEG-SII were correlated with adverse neurodevelopment. Conclusions Low oxygen levels and high FiO2 need during the NICU care associate with WM abnormalities, whereas higher oxygen levels correlate with abnormal MEG-SII. The results may indicate certain brain structures being more vulnerable to hypoxia and others to hyperoxia, thus emphasizing the role of strict saturation targets. Impact This study indicates that both abnormally low and high oxygen levels during early NICU care are harmful for later neurodevelopmental outcomes in preterm neonates. Specific brain structures seem to be vulnerable to low and others to high oxygen levels. The findings may have clinical implications as oxygen is one of the most common therapies given in NICUs. The results emphasize the role of strict saturation targets during the early postnatal period in preterm infants.

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Peptides Derived from Growth Factors to Treat Alzheimer’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22116071 ◽

2021 ◽

Vol 22 (11) ◽

pp. 6071

Author(s):

Suzanne Gascon ◽

Jessica Jann ◽

Chloé Langlois-Blais ◽

Mélanie Plourde ◽

Christine Lavoie ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Growth Factors ◽

Signaling Pathways ◽

Brain Structures ◽

Therapeutic Strategies ◽

Native Proteins ◽

Receptor Sites ◽

The Brain

Alzheimer’s disease (AD) is a devastating neurodegenerative disease characterized by progressive neuron losses in memory-related brain structures. The classical features of AD are a dysregulation of the cholinergic system, the accumulation of amyloid plaques, and neurofibrillary tangles. Unfortunately, current treatments are unable to cure or even delay the progression of the disease. Therefore, new therapeutic strategies have emerged, such as the exogenous administration of neurotrophic factors (e.g., NGF and BDNF) that are deficient or dysregulated in AD. However, their low capacity to cross the blood–brain barrier and their exorbitant cost currently limit their use. To overcome these limitations, short peptides mimicking the binding receptor sites of these growth factors have been developed. Such peptides can target selective signaling pathways involved in neuron survival, differentiation, and/or maintenance. This review focuses on growth factors and their derived peptides as potential treatment for AD. It describes (1) the physiological functions of growth factors in the brain, their neuronal signaling pathways, and alteration in AD; (2) the strategies to develop peptides derived from growth factor and their capacity to mimic the role of native proteins; and (3) new advancements and potential in using these molecules as therapeutic treatments for AD, as well as their limitations.

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Consciousness, decision making, and volition: freedom beyond chance and necessity

Theory in Biosciences ◽

10.1007/s12064-021-00346-6 ◽

2021 ◽

Author(s):

Hans Liljenström

Keyword(s):

Decision Making ◽

Free Will ◽

Brain Activity ◽

Brain Structures ◽

Complex Process ◽

Neural Information ◽

Neural Information Processing ◽

Stochastic Population Model ◽

The Brain

AbstractWhat is the role of consciousness in volition and decision-making? Are our actions fully determined by brain activity preceding our decisions to act, or can consciousness instead affect the brain activity leading to action? This has been much debated in philosophy, but also in science since the famous experiments by Libet in the 1980s, where the current most common interpretation is that conscious free will is an illusion. It seems that the brain knows, up to several seconds in advance what “you” decide to do. These studies have, however, been criticized, and alternative interpretations of the experiments can be given, some of which are discussed in this paper. In an attempt to elucidate the processes involved in decision-making (DM), as an essential part of volition, we have developed a computational model of relevant brain structures and their neurodynamics. While DM is a complex process, we have particularly focused on the amygdala and orbitofrontal cortex (OFC) for its emotional, and the lateral prefrontal cortex (LPFC) for its cognitive aspects. In this paper, we present a stochastic population model representing the neural information processing of DM. Simulation results seem to confirm the notion that if decisions have to be made fast, emotional processes and aspects dominate, while rational processes are more time consuming and may result in a delayed decision. Finally, some limitations of current science and computational modeling will be discussed, hinting at a future development of science, where consciousness and free will may add to chance and necessity as explanation for what happens in the world.

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Pathology, Phenomenology and the Dopamine Hypothesis of Schizophrenia

The British Journal of Psychiatry ◽

10.1192/bjp.151.3.288 ◽

1987 ◽

Vol 151 (3) ◽

pp. 288-301 ◽

Cited By ~ 103

Author(s):

P. J. McKenna

Keyword(s):

Prefrontal Cortex ◽

Basal Ganglia ◽

Functional Role ◽

Ventral Striatum ◽

Brain Structures ◽

Schizophrenic Symptom ◽

Dopamine Hypothesis ◽

Dopamine Innervation

The dopamine hypothesis of schizophrenia implies that positive schizophrenic symptoms should be understandable by reference to brain structures receiving a dopamine innervation, or in terms of the functional role of dopamine itself. The basal ganglia, ventral striatum, septo-hippocampal system, and prefrontal cortex, sites of mesotelencephalic dopamine innervation, are examined and it is argued that their dysfunction could form the basis of particular schizophrenic symptom classes. The postulated involvement of dopamine in reinforcement processes might further assist such interpretations. This type of analysis can be extended to other categories of schizophrenic psychopathology.

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The endocannabinoid system in modulating fear, anxiety, and stress

Dialogues in Clinical Neuroscience ◽

10.31887/dcns.2020.22.3/rmaldonado ◽

2020 ◽

Vol 22 (3) ◽

pp. 229-239

Keyword(s):

Emotional Disorders ◽

Stress Responses ◽

Emotional Responses ◽

Endocannabinoid System ◽

Brain Structures ◽

Therapeutic Implications ◽

Cortical Areas ◽

Prefrontal Cortical ◽

Pathophysiological Role

The endocannabinoid system is widely expressed in the limbic system, prefrontal cortical areas, and brain structures regulating neuroendocrine stress responses, which explains the key role of this system in the control of emotions. In this review, we update recent advances on the function of the endocannabinoid system in determining the value of fear-evoking stimuli and promoting appropriate behavioral responses for stress resilience. We also review the alterations in the activity of the endocannabinoid system during fear, stress, and anxiety, and the pathophysiological role of each component of this system in the control of these protective emotional responses that also trigger pathological emotional disorders. In spite of all the evidence, we have not yet taken advantage of the therapeutic implications of this important role of the endocannabinoid system, and possible future strategies to improve the treatment of these emotional disorders are discussed.

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Role of the Dopaminergic System in the Striatum and Its Association With Functional Recovery or Rehabilitation After Brain Injury

Frontiers in Neuroscience ◽

10.3389/fnins.2021.693404 ◽

2021 ◽

Vol 15 ◽

Author(s):

Antonio Verduzco-Mendoza ◽

Paul Carrillo-Mora ◽

Alberto Avila-Luna ◽

Arturo Gálvez-Rosas ◽

Adriana Olmos-Hernández ◽

...

Keyword(s):

Brain Injury ◽

Functional Recovery ◽

Dopaminergic System ◽

Brain Structures ◽

Receptor Activation ◽

Important Goal ◽

Dopaminergic Drugs ◽

Beneficial Effects ◽

Severe Tbi

Disabilities are estimated to occur in approximately 2% of survivors of traumatic brain injury (TBI) worldwide, and disability may persist even decades after brain injury. Facilitation or modulation of functional recovery is an important goal of rehabilitation in all patients who survive severe TBI. However, this recovery tends to vary among patients because it is affected by the biological and physical characteristics of the patients; the types, doses, and application regimens of the drugs used; and clinical indications. In clinical practice, diverse dopaminergic drugs with various dosing and application procedures are used for TBI. Previous studies have shown that dopamine (DA) neurotransmission is disrupted following moderate to severe TBI and have reported beneficial effects of drugs that affect the dopaminergic system. However, the mechanisms of action of dopaminergic drugs have not been completely clarified, partly because dopaminergic receptor activation can lead to restoration of the pathway of the corticobasal ganglia after injury in brain structures with high densities of these receptors. This review aims to provide an overview of the functionality of the dopaminergic system in the striatum and its roles in functional recovery or rehabilitation after TBI.

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In amygdala we trust: different contributions of the basolateral and central amygdala in learning whom to trust

10.1101/2021.05.03.442429 ◽

2021 ◽

Author(s):

Ronald Sladky ◽

Federica Riva ◽

Lisa Rosenberger ◽

Jack van Honk ◽

Claus Lamm

Keyword(s):

Basolateral Amygdala ◽

Human Subjects ◽

Brain Structures ◽

Trust Game ◽

Rodent Models ◽

Mutual Trust ◽

Central Amygdala ◽

Interaction Partners ◽

Improved Learning

Human societies are built on cooperation and mutual trust, but not everybody is trustworthy. Research on rodents suggests an essential role of the basolateral amygdala (BLA) in learning from social experiences (Hernandez-Lallement J et al., 2016), which was also confirmed in human subjects with selective bilateral BLA damage as they failed to adapt their trust behavior towards trustworthy vs. untrustworthy interaction partners (Rosenberger LA et al., 2019). However, neuroimaging in neurotypical populations did not consistently report involvement of the amygdala in trust behavior. This might be explained by the difficulty of differentiating between amygdala's structurally and functionally different subnuclei, i.e., the BLA and central amygdala (CeA), which have even antagonistic features particularly in trust behavior (van Honk J et al., 2013). Here, we used fMRI of the amygdala subnuclei of neurotypical adults (n=31f/31m) engaging in the repeated trust game. Our data show that both the BLA and the CeA play a role and indeed differentially: While the BLA was most active when obtaining feedback on whether invested trust had been reciprocated or not, the CeA was most active when subjects were preparing their next trust decision. In the latter phase, improved learning was associated with higher activation differences in response to untrustworthy vs. trustworthy trustees, in both BLA and CeA. Our data not only translate to rodent models and support our earlier findings in BLA-damaged subjects, but also show the specific contributions of other brain structures in the amygdala-centered network in learning whom to trust, and better not to trust.

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The time when the “Tomte” of evolution was playing with time

Behavioral and Brain Sciences ◽

10.1017/s0140525x0131395x ◽

2001 ◽

Vol 24 (2) ◽

pp. 287-287

Author(s):

Giorgio M. Innocenti

Keyword(s):

Developmental Plasticity ◽

Brain Structures ◽

Developmental Constraints ◽

Developmental Mechanisms ◽

Differential Expansion ◽

High Degree ◽

Adaptive Role

Developmental constraints presumably had a major role in channeling evolution. In particular, developmental mechanisms may have coordinated the evolution of neocortex with that of other brain structures. However, the rules determining the differential expansion of different cortical territories remain to be determined as well as the adaptive role of cortical expansion versus that of the structures it is connected to. The high degree of developmental plasticity of neocortex was probably the key to its successful evolution.

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