scholarly journals Dysfunction of grey matter NG2 glial cells affects neuronal plasticity and behavior

2021 ◽  
Author(s):  
Aline Timmermann ◽  
Ronald Jabs ◽  
Anne Boehlen ◽  
Catia Domingos ◽  
Magdalena Skubal ◽  
...  
Keyword(s):  
Synaptic Input ◽  
Grey Matter ◽  
Distinct Type ◽  
Long Term Potentiation ◽  
Normal Brain ◽  
Targeted Deletion ◽  
Term Potentiation ◽  
Normal Brain Function ◽  
Physiological Impact ◽  
And Behavior

NG2 glia represent a distinct type of macroglial cells in the CNS and are unique among glia because they receive synaptic input from neurons. They are abundantly present in white and grey matter. While the majority of white matter NG2 glia differentiates into oligodendrocytes, the physiological impact of grey matter NG2 glia and their synaptic input are ill defined yet. Here we asked whether dysfunctional NG2 glia affect neuronal signaling and behavior. We generated mice with inducible deletion of the K+ channel Kir4.1 in NG2 glia and performed comparative electrophysiological, immunohistochemical, molecular and behavioral analyses. Focussing on the hippocampus, we found that loss of the Kir4.1 potentiated synaptic depolarizations of NG2 glia and enhanced the expression of myelin basic protein. Notably, while mice with targeted deletion of the K+ channel in NG2 glia showed impaired long term potentiation at CA3-CA1 synapses, they demonstrated improved spatial memory as revealed by testing new object location recognition. Our data demonstrate that proper NG2 glia function is critical for normal brain function and behavior.

scholarly journals Serine Racemase Deletion Affects the Excitatory/Inhibitory Balance of the Hippocampal CA1 Network

2020 ◽  
Vol 21 (24) ◽  
pp. 9447
Author(s):  
Eva Ploux ◽  
Valentine Bouet ◽  
Inna Radzishevsky ◽  
Herman Wolosker ◽  
Thomas Freret ◽  
...  
Keyword(s):  
Cognitive Abilities ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Reference Memory ◽  
Serine Racemase ◽  
Targeted Deletion ◽  
Term Potentiation ◽  
Hippocampal Ca1 ◽  
The One ◽  
Hippocampal Networks

d-serine is the major co-agonist of N-methyl-D-aspartate receptors (NMDAR) at CA3/CA1 hippocampal synapses, the activation of which drives long-term potentiation (LTP). The use of mice with targeted deletion of the serine racemase (SR) enzyme has been an important tool to uncover the physiological and pathological roles of D-serine. To date, some uncertainties remain regarding the direction of LTP changes in SR-knockout (SR-KO) mice, possibly reflecting differences in inhibitory GABAergic tone in the experimental paradigms used in the different studies. On the one hand, our extracellular recordings in hippocampal slices show that neither isolated NMDAR synaptic potentials nor LTP were altered in SR-KO mice. This was associated with a compensatory increase in hippocampal levels of glycine, another physiologic NMDAR co-agonist. SR-KO mice displayed no deficits in spatial learning, reference memory and cognitive flexibility. On the other hand, SR-KO mice showed a weaker LTP and a lower increase in NMDAR potentials compared to controls when GABAA receptors were pharmacologically blocked. Our results indicate that depletion of endogenous D-serine caused a reduced inhibitory activity in CA1 hippocampal networks, altering the excitatory/inhibitory balance, which contributes to preserve functional plasticity at synapses and to maintain related cognitive abilities.

scholarly journals A physiological role for GABAA receptor desensitization – induction of long-term potentiation at inhibitory synapses

2020 ◽  
Author(s):  
Martin Field ◽  
Philip Thomas ◽  
Trevor G Smart
Keyword(s):  
Physiological Role ◽  
Long Term Potentiation ◽  
Inhibitory Synapses ◽  
Structural Basis ◽  
Inhibitory Neurotransmission ◽  
Term Potentiation ◽  
Physiological Relevance ◽  
Kinetic Effects ◽  
Physiological Impact

AbstractGABAA receptors (GABAARs) are pentameric ligand-gated ion channels distributed throughout the brain where they mediate synaptic and tonic inhibition. Following activation, these receptors undergo desensitization which involves entry into long-lived agonist-bound closed states. Although the kinetic effects of this state are recognised and its structural basis has been uncovered, the physiological impact of desensitization on inhibitory neurotransmission remains unknown. Here we describe an enduring new form of long-term potentiation at inhibitory synapses that elevates synaptic current amplitude for 24 hrs following desensitization of GABAARs in response to prolonged agonist exposure or allosteric modulation. Using receptor mutants and allosteric modulators we demonstrate that desensitization of GABAARs facilitates their phosphorylation by PKC, which increases the number of receptors at inhibitory synapses. These observations provide a new physiological relevance to the desensitized state of GABAARs, acting as a signal to regulate the efficacy of inhibitory synapses during prolonged periods of inhibitory neurotransmission.

scholarly journals IL-37 expression reduces acute and chronic neuroinflammation and rescues cognitive impairment in an Alzheimer s disease mouse model

2021 ◽  
Author(s):  
Niklas Lonnemann ◽  
Shirin Hosseini ◽  
Melanie Ohm ◽  
Karsten Hiller ◽  
Charles A. Dinarello ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cognitive Abilities ◽  
Long Term Potentiation ◽  
Spine Density ◽  
Chronic Neuroinflammation ◽  
Model Of Alzheimer’S Disease ◽  
Term Potentiation ◽  
Anti Inflammatory ◽  
And Function ◽  
And Behavior

The anti-inflammatory cytokine interleukin-37 (IL-37) is a member of the IL-1 family but not expressed in mice. We used a human IL 37 (hIL-37tg) expressing mouse, which has been subjected to various models of local and systemic inflammation as well as immunological challenges. Those studies demonstrate an immune-modulatory role of IL-37 which can be characterized as an important suppressor of innate immunity. We investigated the functions of IL-37 in the CNS and explored the effects of IL-37 on neuronal architecture and function, microglia phenotype, cytokine production and behavior after inflammatory challenge by intraperitoneal LPS-injection. Reduced spine density, activated microglia phenotype and impaired long-term potentiation (LTP) were observed in wild-type mice after LPS injection, whereas hIL-37tg mice showed no impairment. In addition, we crossed the hIL-37tg mouse with an animal model of Alzheimer's disease (APP/PS1) to investigate the anti-inflammatory properties of IL-37 under chronic neuroinflammatory conditions. Our results show that IL-37 is able to limit inflammation in the brain after acute inflammatory events and prevent the loss of cognitive abilities in a mouse model of AD.

scholarly journals Activity-dependent tuning of intrinsic excitability in mouse and human neurogliaform cells

2020 ◽  
Author(s):  
R. Chittajallu ◽  
K. Auville ◽  
V. Mahadevan ◽  
M. Lai ◽  
S. Hunt ◽  
...  
Keyword(s):  
Cognitive Processing ◽  
Intrinsic Excitability ◽  
Inhibitory Influence ◽  
Essential Property ◽  
Normal Brain ◽  
Cellular Mechanisms ◽  
Normal Brain Function ◽  
Circuit Function ◽  
And Behavior ◽  
Activity Dependent

ABSTRACTThe ability to modulate the efficacy of synaptic communication between neurons constitutes an essential property critical for normal brain function. Animal models have proved invaluable in revealing a wealth of diverse cellular mechanisms underlying varied plasticity modes. However, to what extent these processes are mirrored in humans is largely uncharted thus questioning their relevance to human circuit function. In this study, we focus on neurogliaform cells, a specialized form of neuron that possess physiological features enabling them to impart a widespread inhibitory influence on neural activity. We demonstrate that this prominent neuronal subtype, embedded in both mouse and human neural circuits, undergo remarkably similar activity-dependent modulation manifesting as epochs of enhanced intrinsic excitability. In principle, these evolutionary conserved plasticity routes likely tune the extent of neurogliaform cell mediated inhibition thus constituting canonical circuit mechanisms relevant for human cognitive processing and behavior.

scholarly journals HEBB'S THEORY OF LEARNING IN COGNITIVE NEUROSCIENCE

2021 ◽  
Vol 03 (05) ◽  
pp. 259-265
Author(s):  
Ali Salim Rashid ALGHAFRI
Keyword(s):  
Cognitive Neuroscience ◽  
Long Term Potentiation ◽  
Cell Assembly ◽  
Learning Behavior ◽  
Brain Neuron ◽  
Term Potentiation ◽  
Mechanism Of Interaction ◽  
And Behavior ◽  
Hebb Learning

Donald Hebb who is the founder of theory of learning behavior from the perspective of cognitive neuroscience based on the cell assembly. Where he explained the occurrence of learning through the Hebb's synapse, which explained the mechanism of interaction and connection between synaptic cells, and the activity that occurs between them to produce learning and related thinking and memory. Also, how the induce that occurs between the cell assembly in the Hebb's synapse has a significant role to understand learning and associated skills, abilities and behavior. Therefore, this theory in the field of education and psychology was employed in the mechanism of long-term Potentiation (LTP) to interpret the occurrence of learning in terms of cognitive neuroscience. Keywords: Cognitive Neuroscience, Theory, Hebb, Learning, Teaching, Brain, Neuron

scholarly journals Input-specific NMDAR-dependent potentiation of dendritic GABAergic inhibition

2017 ◽  
Author(s):  
Chiayu Q. Chiu ◽  
James S. Martenson ◽  
Maya Yamazaki ◽  
Rie Natsume ◽  
Kenji Sakimura ◽  
...  
Keyword(s):  
Long Term Potentiation ◽  
Inhibitory Synapses ◽  
Inhibitory Input ◽  
Normal Brain ◽  
Cellular Mechanisms ◽  
Gaba A ◽  
Neuronal Dendrites ◽  
Normal Brain Function

SummaryPreservation of a balance between synaptic excitation and inhibition is critical for normal brain function. A number of homeostatic cellular mechanisms have been suggested to play a role in maintaining this balance, including long-term plasticity of GABAergic inhibitory synapses. Many previous studies have demonstrated a coupling of postsynaptic spiking with modification of perisomatic inhibition. Here, we demonstrate that activation of NMDA-type glutamate receptors leads to input-specific long-term potentiation of dendritic inhibition mediated by somatostatin-expressing interneurons. This form of plasticity is expressed postsynaptically and requires both CaMKIIα and the β2-subunit of the GABA-A receptor. Importantly, this process may function to preserve dendritic inhibition, as in vivo loss of NMDAR signaling results in a selective weakening of dendritic inhibition. Overall, our results reveal a new mechanism for linking excitatory and inhibitory input in neuronal dendrites and provide novel insight into the homeostatic regulation of synaptic transmission in cortical circuits.

scholarly journals Atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniella B. Victorino ◽  
Daniel J. L. L. Pinheiro ◽  
Jonah J. Scott-McKean ◽  
Sarah Barker ◽  
Melissa R. Stasko ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Mouse Model ◽  
Brain Activity ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Plus Maze ◽  
Underlying Causes ◽  
Pre Treatment ◽  
And Behavior

AbstractMounting evidence implicates dysfunctional GABAAR-mediated neurotransmission as one of the underlying causes of learning and memory deficits observed in the Ts65Dn mouse model of Down syndrome (DS). The specific origin and nature of such dysfunction is still under investigation, which is an issue with practical consequences to preclinical and clinical research, as well as to the care of individuals with DS and anxiety disorder or those experiencing seizures in emergency room settings. Here, we investigated the effects of GABAAR positive allosteric modulation (PAM) by diazepam on brain activity, synaptic plasticity, and behavior in Ts65Dn mice. We found Ts65Dn mice to be less sensitive to diazepam, as assessed by electroencephalography, long-term potentiation, and elevated plus-maze. Still, diazepam pre-treatment displayed typical effectiveness in reducing susceptibility and severity to picrotoxin-induced seizures in Ts65Dn mice. These findings fill an important gap in the understanding of GABAergic function in a key model of DS.

scholarly journals Topoisomerase IIIβ Deficiency Induces Neuro-Behavioral Changes and Brain Connectivity Alterations in Mice

2021 ◽  
Vol 22 (23) ◽  
pp. 12806
Author(s):  
Faiz Ur Rahman ◽  
You-Rim Kim ◽  
Eun-Kyeung Kim ◽  
Hae-rim Kim ◽  
Sang-Mi Cho ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Brain Connectivity ◽  
Brain Regions ◽  
Normal Brain ◽  
Dna And Rna ◽  
Positron Emission ◽  
Normal Brain Function ◽  
Ct Analysis ◽  
The Central Nervous System ◽  
And Behavior

Topoisomerase IIIβ (Top3β), the only dual-activity topoisomerase in mammals that can change topology of both DNA and RNA, is known to be associated with neurodevelopment and mental dysfunction in humans. However, there is no report showing clear associations of Top3β with neuropsychiatric phenotypes in mice. Here, we investigated the effect of Top3β on neuro-behavior using newly generated Top3β deficient (Top3β−/−) mice. We found that Top3β−/− mice showed decreased anxiety and depression-like behaviors. The lack of Top3β was also associated with changes in circadian rhythm. In addition, a clear expression of Top3β was demonstrated in the central nervous system of mice. Positron emission tomography/computed tomography (PET/CT) analysis revealed significantly altered connectivity between many brain regions in Top3β−/− mice, including the connectivity between the olfactory bulb and the cerebellum, the connectivity between the amygdala and the olfactory bulb, and the connectivity between the globus pallidus and the optic nerve. These connectivity alterations in brain regions are known to be linked to neurodevelopmental as well as psychiatric and behavioral disorders in humans. Therefore, we conclude that Top3β is essential for normal brain function and behavior in mice and that Top3β could be an interesting target to study neuropsychiatric disorders in humans.

Sign in / Sign up

Export Citation Format

Share Document