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

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ramesh Chittajallu ◽  
Kurt Auville ◽  
Vivek Mahadevan ◽  
Mandy Lai ◽  
Steven Hunt ◽  
...  
Keyword(s):  
Cognitive Processing ◽  
Intrinsic Excitability ◽  
Inhibitory Influence ◽  
Essential Property ◽  
Normal Brain ◽  
Cellular Mechanisms ◽  
Normal Brain Function ◽  
Circuit Function ◽  
And Behavior ◽  
Activity Dependent

The 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 in human circuit function. In this study, we focus on neurogliaform cells, that possess specialized 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 underlying human cognitive processing and behavior.

scholarly journals Defective Neuronal Positioning Correlates With Aberrant Motor Circuit Function in Zebrafish

2021 ◽  
Vol 15 ◽  
Author(s):  
Emilia Asante ◽  
Devynn Hummel ◽  
Suman Gurung ◽  
Yasmin M. Kassim ◽  
Noor Al-Shakarji ◽  
...  
Keyword(s):  
Neuromuscular Junctions ◽  
Larval Feeding ◽  
Normal Brain ◽  
Axon Pathfinding ◽  
Loss Of Function ◽  
Jaw Muscles ◽  
Normal Brain Function ◽  
Functional Consequences ◽  
And Migration ◽  
Circuit Function

Precise positioning of neurons resulting from cell division and migration during development is critical for normal brain function. Disruption of neuronal migration can cause a myriad of neurological disorders. To investigate the functional consequences of defective neuronal positioning on circuit function, we studied a zebrafish frizzled3a (fzd3a) loss-of-function mutant off-limits (olt) where the facial branchiomotor (FBM) neurons fail to migrate out of their birthplace. A jaw movement assay, which measures the opening of the zebrafish jaw (gape), showed that the frequency of gape events, but not their amplitude, was decreased in olt mutants. Consistent with this, a larval feeding assay revealed decreased food intake in olt mutants, indicating that the FBM circuit in mutants generates defective functional outputs. We tested various mechanisms that could generate defective functional outputs in mutants. While fzd3a is ubiquitously expressed in neural and non-neural tissues, jaw cartilage and muscle developed normally in olt mutants, and muscle function also appeared to be unaffected. Although FBM neurons were mispositioned in olt mutants, axon pathfinding to jaw muscles was unaffected. Moreover, neuromuscular junctions established by FBM neurons on jaw muscles were similar between wildtype siblings and olt mutants. Interestingly, motor axons innervating the interhyoideus jaw muscle were frequently defasciculated in olt mutants. Furthermore, GCaMP imaging revealed that mutant FBM neurons were less active than their wildtype counterparts. These data show that aberrant positioning of FBM neurons in olt mutants is correlated with subtle defects in fasciculation and neuronal activity, potentially generating defective functional outputs.

scholarly journals Multiple shared mechanisms for homeostatic plasticity in rodent somatosensory and visual cortex

2017 ◽  
Vol 372 (1715) ◽  
pp. 20160157 ◽  
Author(s):  
Melanie A. Gainey ◽  
Daniel E. Feldman
Keyword(s):  
Visual Cortex ◽  
Sensory Deprivation ◽  
Homeostatic Plasticity ◽  
Intrinsic Excitability ◽  
Synaptic Scaling ◽  
Cellular Mechanisms ◽  
Firing Rates ◽  
Parvalbumin Interneuron ◽  
Activity Dependent ◽  
V1 Cortex

We compare the circuit and cellular mechanisms for homeostatic plasticity that have been discovered in rodent somatosensory (S1) and visual (V1) cortex. Both areas use similar mechanisms to restore mean firing rate after sensory deprivation. Two time scales of homeostasis are evident, with distinct mechanisms. Slow homeostasis occurs over several days, and is mediated by homeostatic synaptic scaling in excitatory networks and, in some cases, homeostatic adjustment of pyramidal cell intrinsic excitability. Fast homeostasis occurs within less than 1 day, and is mediated by rapid disinhibition, implemented by activity-dependent plasticity in parvalbumin interneuron circuits. These processes interact with Hebbian synaptic plasticity to maintain cortical firing rates during learned adjustments in sensory representations. This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity’.

scholarly journals Interplay of Good Bacteria and Central Nervous System: Cognitive Aspects and Mechanistic Considerations

2021 ◽  
Vol 15 ◽  
Author(s):  
Mahmoud Salami
Keyword(s):  
Gut Microbiota ◽  
Cognitive Processing ◽  
Clinical Problem ◽  
The Body ◽  
Brain Diseases ◽  
Normal Brain ◽  
Beneficial Effects ◽  
Normal Brain Function ◽  
The Brain ◽  
Common Clinical Problem

The human gastrointestinal tract hosts trillions of microorganisms that is called “gut microbiota.” The gut microbiota is involved in a wide variety of physiological features and functions of the body. Thus, it is not surprising that any damage to the gut microbiota is associated with disorders in different body systems. Probiotics, defined as living microorganisms with health benefits for the host, can support or restore the composition of the gut microbiota. Numerous investigations have proved a relationship between the gut microbiota with normal brain function as well as many brain diseases, in which cognitive dysfunction is a common clinical problem. On the other hand, increasing evidence suggests that the existence of a healthy gut microbiota is crucial for normal cognitive processing. In this regard, interplay of the gut microbiota and cognition has been under focus of recent researches. In the present paper, I review findings of the studies considering beneficial effects of either gut microbiota or probiotic bacteria on the brain cognitive function in the healthy and disease statuses.

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 Fast Oscillations and Epilepsy

2003 ◽  
Vol 3 (3) ◽  
pp. 77-79 ◽  
Author(s):  
Roger D. Traub
Keyword(s):  
Experimental Data ◽  
Brain Function ◽  
Epileptic Seizures ◽  
Normal Brain ◽  
Cellular Mechanisms ◽  
Normal Brain Function ◽  
Fast Oscillations

Very fast oscillations, 80 Hz and greater (designated here VFOs or “ripples”) have been observed in the hippocampus and neocortex, under a variety of conditions that are summarized briefly later. VFOs may be of relevance for normal brain function ( 1 – 4 ) and could also be of relevance in the initiation of focal epileptic seizures ( 5 , 6 ). To determine whether such relevance indeed exists, an understanding of the cellular mechanisms of VFOs is essential. For purposes of this commentary, I shall assume that all forms of VFOs are governed by a few common basic underlying principles. Future experimental data may show that assumption to be false, but for now, the assumption at least allows the formulation of straightforward hypotheses that could stimulate experiments.

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 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.

scholarly journals Synchrony surfacing: epicortical recording of correlated action potentials

2018 ◽  
Author(s):  
Tobias Bockhorst ◽  
Florian Pieper ◽  
Gerhard Engler ◽  
Thomas Stieglitz ◽  
Edgar Galindo-Leon ◽  
...  
Keyword(s):  
Cognitive Processing ◽  
Action Potentials ◽  
Sensory Stimulation ◽  
Brain Network ◽  
Low Noise ◽  
Normal Brain ◽  
Cortical Surface ◽  
Normal Brain Function ◽  
Sensory Cortices ◽  
Machine Interface

AbstractSynchronous spiking of multiple neurons is a key phenomenon in normal brain function and pathologies. Recently, approaches to record spikes from the intact cortical surface using small high-density arrays of microelectrodes have been reported. It remained unaddressed how epicortical spiking relates to intracortical unit activity. We introduce a mesoscale approach using an array of 64 electrodes with intermediate diameter (250 µm) and combined large-coverage epicortical recordings in ferrets with intracortical recordings via laminar probes. Empirical data and modeling strongly suggest that our epicortical electrodes selectively captured synchronized spiking of neurons in the subjacent cortex. As a result, responses to sensory stimulation were more robust and less noisy as compared to intracortical activity, and receptive field properties were well preserved in epicortical recordings. This should promote insights into assembly-coding beyond the informative value of subdural EEG or single-unit spiking, and be advantageous to real-time applications in brain-machine interfacing.Significance statementElectrocorticography allows chronic, low-noise recordings from the intact cortical surface - a prerequisite for investigations into brain network dynamics and brain-machine interfaces. Novel electrodes can capture spiking activity at the surface, which should boost precision in the spatial - and time domain, compared to conventional EEG-like measurements. To clarify how surface spiking relates to intracortically fired action potentials, we recorded both types of signal simultaneously from sensory cortices in anesthetized ferrets. Results suggest that mesoscale (250 µm) surface electrodes can selectively capture synchronized spiking from nearby cortical columns, which reduces contamination by non-representative, jittering spikes. Given the high relevance of neural synchrony for sensorimotor and cognitive processing, the novel methodology may improve signal decoding in brain-machine interface approaches.Author contributionsE.G.L., T.B. and A.K.E. conceptualized the research; E.G.L. and F.P. performed experiments; T.B. and E.G.L. wrote Matlab routines for data analysis; T.B. and E.G.L. analyzed the data; T.S. provided technical resources; T.B., E.G.L. and A.K.E. wrote the manuscript; G.E. administrated the project; A.K.E. acquired funding.

scholarly journals Mature parvalbumin interneuron function in prefrontal cortex requires activity during a postnatal sensitive period

2021 ◽  
Author(s):  
Sarah E Canetta ◽  
Emma S Holt ◽  
Laura J Benoit ◽  
Eric Teboul ◽  
R. Todd Ogden ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Sensitive Period ◽  
Network Function ◽  
Parvalbumin Interneuron ◽  
Circuit Integration ◽  
Circuit Function ◽  
And Behavior ◽  
Activity Dependent

Sensitive periods in which experience-driven changes in activity persistently shape circuit function are well-described in sensory cortex. Whether comparable periods govern the development of associative cortical areas, like the prefrontal cortex, remains unclear. Here, we focus on the role of activity in the maturation and circuit integration of prefrontal parvalbumin-expressing interneurons, as these cells play an essential role in sensory cortical maturation and develop in lockstep with overall prefrontal circuit function. We found that transiently decreasing prefrontal parvalbumin activity during peripubertal and adolescent development results in persistent impairments in adult functional connectivity, in vivo network function and set-shifting behavior that can be rescued by targeted activation of these interneurons in the adult animal. In contrast, comparable adult inhibition had no lasting effects. These findings identify an activity-dependent sensitive period for prefrontal parvalbumin maturation and highlight how abnormal parvalbumin activity early in life can persistently alter adult circuit function and behavior.

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