scholarly journals Mild metabolic stress is sufficient to disturb the formation of pyramidal cell ensembles during gamma oscillations

2019 ◽  
Vol 40 (12) ◽  
pp. 2401-2415 ◽  
Author(s):  
Shehabeldin Elzoheiry ◽  
Andrea Lewen ◽  
Justus Schneider ◽  
Martin Both ◽  
Dimitri Hefter ◽  
...  
Keyword(s):  
Pyramidal Cell ◽  
Metabolic Stress ◽  
Pyramidal Cells ◽  
Gamma Oscillations ◽  
System Level ◽  
Attention And Memory ◽  
Neuronal Ensembles ◽  
Brain Functions ◽  
Fast Spiking ◽  
Underlying Mechanisms

Disturbances of cognitive functions occur rapidly during acute metabolic stress. However, the underlying mechanisms are not fully understood. Cortical gamma oscillations (30–100 Hz) emerging from precise synaptic transmission between excitatory principal neurons and inhibitory interneurons, such as fast-spiking GABAergic basket cells, are associated with higher brain functions, like sensory perception, selective attention and memory formation. We investigated the alterations of cholinergic gamma oscillations at the level of neuronal ensembles in the CA3 region of rat hippocampal slice cultures. We combined electrophysiology, calcium imaging (CamKII.GCaMP6f) and mild metabolic stress that was induced by rotenone, a lipophilic and highly selective inhibitor of complex I in the respiratory chain of mitochondria. The detected pyramidal cell ensembles showing repetitive patterns of activity were highly sensitive to mild metabolic stress. Whereas such synchronised multicellular activity diminished, the overall activity of individual pyramidal cells was unaffected. Additionally, mild metabolic stress had no effect on the rate of action potential generation in fast-spiking neural units. However, the partial disinhibition of slow-spiking neural units suggests that disturbances of ensemble formation likely result from alterations in synaptic inhibition. Our study bridges disturbances on the (multi-)cellular and network level to putative cognitive impairment on the system level.

scholarly journals Highly Energized Inhibitory Interneurons are a Central Element for Information Processing in Cortical Networks

2014 ◽  
Vol 34 (8) ◽  
pp. 1270-1282 ◽  
Author(s):  
Oliver Kann ◽  
Ismini E Papageorgiou ◽  
Andreas Draguhn
Keyword(s):  
Information Processing ◽  
Motor Behavior ◽  
Central Element ◽  
Metabolic Stress ◽  
Pyramidal Cells ◽  
Gamma Oscillations ◽  
High Energy ◽  
Energy Utilization ◽  
Cellular Mechanisms ◽  
Fast Spiking

Gamma oscillations (~30 to 100 Hz) provide a fundamental mechanism of information processing during sensory perception, motor behavior, and memory formation by coordination of neuronal activity in networks of the hippocampus and neocortex. We review the cellular mechanisms of gamma oscillations about the underlying neuroenergetics, i.e., high oxygen consumption rate and exquisite sensitivity to metabolic stress during hypoxia or poisoning of mitochondrial oxidative phosphorylation. Gamma oscillations emerge from the precise synaptic interactions of excitatory pyramidal cells and inhibitory GABAergic interneurons. In particular, specialized interneurons such as parvalbumin-positive basket cells generate action potentials at high frequency (‘fast-spiking’) and synchronize the activity of numerous pyramidal cells by rhythmic inhibition (‘clockwork’). As prerequisites, fast-spiking interneurons have unique electrophysiological properties and particularly high energy utilization, which is reflected in the ultrastructure by enrichment with mitochondria and cytochrome c oxidase, most likely needed for extensive membrane ion transport and γ-aminobutyric acid metabolism. This supports the hypothesis that highly energized fast-spiking interneurons are a central element for cortical information processing and may be critical for cognitive decline when energy supply becomes limited (‘interneuron energy hypothesis’). As a clinical perspective, we discuss the functional consequences of metabolic and oxidative stress in fast-spiking interneurons in aging, ischemia, Alzheimer's disease, and schizophrenia.

scholarly journals Disrupted-in-Schizophrenia-1 is required for proper pyramidal cell-interneuron communication and network dynamics in the prefrontal cortex

2021 ◽  
Author(s):  
Jonas-Frederic Sauer ◽  
Marlene Bartos
Keyword(s):  
Pyramidal Cell ◽  
Gamma Oscillations ◽  
Mutant Mice ◽  
Potential Mechanism ◽  
Excitatory Effect ◽  
Fast Spiking ◽  
Single Unit Recordings ◽  
Circuit Function

AbstractWe interrogated prefrontal circuit function in mice lacking Disrupted-in-schizophrenia-1 (Disc1-mutant mice), a risk factor for psychiatric disorders. Single-unit recordings in awake mice revealed reduced average firing rates of fast-spiking interneurons (INTs), including optogenetically identified parvalbumin-positive cells, and a lower proportion of INTs phase-coupled to ongoing gamma oscillations. Moreover, we observed decreased spike transmission efficacy at local pyramidal cell (PYR)-INT connections in vivo, suggesting a reduced excitatory effect of local glutamatergic inputs as a potential mechanism of lower INT rates. On the network level, impaired INT function resulted in altered activation of PYR assemblies: While assembly activations were observed equally often, the expression strength of individual assembly patterns was significantly higher in Disc1-mutant mice. Our data thus reveal a role of Disc1 in shaping the properties of prefrontal assembly patterns by setting prefrontal INT responsiveness to glutamatergic drive.

scholarly journals Hippocampal-Prefrontal cortex network dynamics predict performance during retrieval in a context-guided object memory task

2021 ◽  
Author(s):  
Juan Facundo Morici ◽  
Noelia Victoria Weisstaub ◽  
Camila Lidia Zold
Keyword(s):  
Prefrontal Cortex ◽  
Contextual Information ◽  
Phase Locking ◽  
Memory Task ◽  
Pyramidal Cells ◽  
Neuronal Ensembles ◽  
Electrophysiological Recordings ◽  
Specific Object ◽  
Underlying Mechanisms ◽  
Amplitude Correlation

Remembering life episodes is a complex process that requires the interaction between multiple brain areas. It is thought that contextual information provided by the hippocampus (HPC) can trigger the recall of a past event through the activation of medial prefrontal cortex (mPFC) neuronal ensembles, but the underlying mechanisms remain poorly understood. Indeed, little is known about how the vHPC and mPFC are coordinated during a contextual-guided recall of an object recognition memory. To address this, we performed electrophysiological recordings in behaving rats during the retrieval phase of the object-in-context memory task (OIC). Coherence, phase locking and theta amplitude correlation analysis showed an increase in vHPC-mPFC LFP synchronization in the theta range when animals explore contextually mismatched objects. Moreover, we identified ensembles of putative pyramidal cells in the mPFC that encode specific object-context associations. Interestingly, the increase of vHPC-mPFC synchronization during exploration of the contextually mismatched object and the preference of mPFC incongruent object neurons predicts the animal's performance during the resolution of the OIC task. Altogether, these results identify changes in vHPC-mPFC synchronization and mPFC ensembles encoding specific object-context associations likely involved in the recall of past events.

scholarly journals The mitochondrial calcium uniporter is crucial for the generation of fast cortical network rhythms

2019 ◽  
Vol 40 (11) ◽  
pp. 2225-2239 ◽  
Author(s):  
Carlos Bas-Orth ◽  
Justus Schneider ◽  
Andrea Lewen ◽  
Jamie McQueen ◽  
Kerstin Hasenpusch-Theil ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Pyramidal Cells ◽  
Gamma Oscillations ◽  
Spike Timing ◽  
Mitochondrial Calcium ◽  
Attention And Memory ◽  
Mitochondrial Calcium Uniporter ◽  
Sharp Waves ◽  
Calcium Uniporter

The role of the mitochondrial calcium uniporter (MCU) gene ( Mcu) in cellular energy homeostasis and generation of electrical brain rhythms is widely unknown. We investigated this issue in mice and rats using Mcu-knockout and -knockdown strategies in vivo and in situ and determined the effects of these genetic manipulations on hippocampal gamma oscillations (30–70 Hz) and sharp wave-ripples. These physiological network states require precise neurotransmission between pyramidal cells and inhibitory interneurons, support spike-timing and synaptic plasticity and are associated with perception, attention and memory. Absence of the MCU resulted in (i) gamma oscillations with decreased power (by >40%) and lower synchrony, including less precise neural action potential generation (‘spiking'), (ii) sharp waves with decreased incidence (by about 22%) and decreased fast ripple frequency (by about 3%) and (iii) lack of activity-dependent pyruvate dehydrogenase dephosphorylation. However, compensatory adaptation in gene expression related to mitochondrial function and glucose metabolism was not detected. These data suggest that the neuronal MCU is crucial for the generation of network rhythms, most likely by influences on oxidative phosphorylation and perhaps by controlling cytoplasmic Ca2+ homeostasis. This work contributes to an increased understanding of mitochondrial Ca2+ uptake in cortical information processing underlying cognition and behaviour.

scholarly journals Roles of specific Kv channel types in repolarization of the action potential in genetically identified subclasses of pyramidal neurons in mouse neocortex

2016 ◽  
Vol 115 (5) ◽  
pp. 2317-2329 ◽  
Author(s):  
Dhruba Pathak ◽  
Dongxu Guan ◽  
Robert C. Foehring
Keyword(s):  
Action Potential ◽  
Pyramidal Cell ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Excitable Cells ◽  
Long Distance ◽  
Cell Subtype ◽  
Layer 2 ◽  
Neuronal Types ◽  
Underlying Mechanisms

The action potential (AP) is a fundamental feature of excitable cells that serves as the basis for long-distance signaling in the nervous system. There is considerable diversity in the appearance of APs and the underlying repolarization mechanisms in different neuronal types (reviewed in Bean BP. Nat Rev Neurosci 8: 451–465, 2007), including among pyramidal cell subtypes. In the present work, we used specific pharmacological blockers to test for contributions of Kv1, Kv2, or Kv4 channels to repolarization of single APs in two genetically defined subpopulations of pyramidal cells in layer 5 of mouse somatosensory cortex ( etv1 and glt) as well as pyramidal cells from layer 2/3. These three subtypes differ in AP properties (Groh A, Meyer HS, Schmidt EF, Heintz N, Sakmann B, Krieger P. Cereb Cortex 20: 826–836, 2010; Guan D, Armstrong WE, Foehring RC. J Neurophysiol 113: 2014–2032, 2015) as well as laminar position, morphology, and projection targets. We asked what the roles of Kv1, Kv2, and Kv4 channels are in AP repolarization and whether the underlying mechanisms are pyramidal cell subtype dependent. We found that Kv4 channels are critically involved in repolarizing neocortical pyramidal cells. There are also pyramidal cell subtype-specific differences in the role for Kv1 channels. Only Kv4 channels were involved in repolarizing the narrow APs of glt cells. In contrast, in etv1 cells and layer 2/3 cells, the broader APs are partially repolarized by Kv1 channels in addition to Kv4 channels. Consistent with their activation in the subthreshold range, Kv1 channels also regulate AP voltage threshold in all pyramidal cell subtypes.

scholarly journals Afferent inputs to cortical fast-spiking interneurons organize pyramidal cell network oscillations at high-gamma frequencies (60–200 Hz)

2014 ◽  
Vol 112 (11) ◽  
pp. 3001-3011 ◽  
Author(s):  
Piotr Suffczynski ◽  
Nathan E. Crone ◽  
Piotr J. Franaszczuk
Keyword(s):  
Local Field ◽  
Local Field Potential ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Gamma Oscillations ◽  
Cortical Activation ◽  
Gamma Activity ◽  
High Gamma ◽  
Fast Spiking ◽  
Gamma Frequencies

High-gamma activity, ranging in frequency between ∼60 Hz and 200 Hz, has been observed in local field potential, electrocorticography, EEG and magnetoencephalography signals during cortical activation, in a variety of functional brain systems. The origin of these signals is yet unknown. Using computational modeling, we show that a cortical network model receiving thalamic input generates high-gamma responses comparable to those observed in local field potential recorded in monkey somatosensory cortex during vibrotactile stimulation. These high-gamma oscillations appear to be mediated mostly by an excited population of inhibitory fast-spiking interneurons firing at high-gamma frequencies and pacing excitatory regular-spiking pyramidal cells, which fire at lower rates but in phase with the population rhythm. The physiological correlates of high-gamma activity, in this model of local cortical circuits, appear to be similar to those proposed for hippocampal ripples generated by subsets of interneurons that regulate the discharge of principal cells.

scholarly journals Functional effects of distinct innervation styles of pyramidal cells by fast spiking cortical interneurons

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Yoshiyuki Kubota ◽  
Satoru Kondo ◽  
Masaki Nomura ◽  
Sayuri Hatada ◽  
Noboru Yamaguchi ◽  
...  
Keyword(s):  
Pyramidal Cell ◽  
Pyramidal Cells ◽  
Physiological Data ◽  
Functional Differences ◽  
Cortical Interneurons ◽  
Fast Spiking ◽  
Functionally Diverse ◽  
Cell Inhibition ◽  
Cell Somata ◽  
Global Inhibition

Inhibitory interneurons target precise membrane regions on pyramidal cells, but differences in their functional effects on somata, dendrites and spines remain unclear. We analyzed inhibitory synaptic events induced by cortical, fast-spiking (FS) basket cells which innervate dendritic shafts and spines as well as pyramidal cell somata. Serial electron micrograph (EMg) reconstructions showed that somatic synapses were larger than dendritic contacts. Simulations with precise anatomical and physiological data reveal functional differences between different innervation styles. FS cell soma-targeting synapses initiate a strong, global inhibition, those on shafts inhibit more restricted dendritic zones, while synapses on spines may mediate a strictly local veto. Thus, FS cell synapses of different sizes and sites provide functionally diverse forms of pyramidal cell inhibition.

scholarly journals Priming of microglia with IFN-γ slows neuronal gamma oscillations in situ

2019 ◽  
Vol 116 (10) ◽  
pp. 4637-4642 ◽  
Author(s):  
Thuy-Truc Ta ◽  
Hasan Onur Dikmen ◽  
Simone Schilling ◽  
Bruno Chausse ◽  
Andrea Lewen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Population Expansion ◽  
Gamma Oscillations ◽  
Attention And Memory ◽  
Activation Process ◽  
Activation Markers ◽  
Brain Functions ◽  
Ifn Γ ◽  
The Impact

Type II IFN (IFN-γ) is a proinflammatory T lymphocyte cytokine that serves in priming of microglia—resident CNS macrophages—during the complex microglial activation process under pathological conditions. Priming generally permits an exaggerated microglial response to a secondary inflammatory stimulus. The impact of primed microglia on physiological neuronal function in intact cortical tissue (in situ) is widely unknown, however. We explored the effects of chronic IFN-γ exposure on microglia in hippocampal slice cultures, i.e., postnatal parenchyma lacking leukocyte infiltration (adaptive immunity). We focused on fast neuronal network waves in the gamma-band (30–70 Hz). Such gamma oscillations are fundamental to higher brain functions, such as perception, attention, and memory, and are exquisitely sensitive to metabolic and oxidative stress. IFN-γ induced substantial morphological changes and cell population expansion in microglia as well as moderate up-regulation of activation markers, MHC-II, CD86, IL-6, and inducible nitric oxide synthase (iNOS), but not TNF-α. Cytoarchitecture and morphology of pyramidal neurons and parvalbumin-positive inhibitory interneurons were well-preserved. Notably, gamma oscillations showed a specific decline in frequency of up to 8 Hz, which was not mimicked by IFN-α or IL-17 exposure. The rhythm disturbance was caused by moderate microglial nitric oxide (NO) release demonstrated by pharmacological microglia depletion and iNOS inhibition. In conclusion, IFN-γ priming induces substantial proliferation and moderate activation of microglia that is capable of slowing neural information processing. This mechanism might contribute to cognitive impairment in chronic brain disease featuring elevated IFN-γ levels, blood–brain barrier leakage, and/or T cell infiltration, well before neurodegeneration occurs.

scholarly journals CA2 inhibition reduces the precision of hippocampal assembly reactivation

2020 ◽  
Author(s):  
Hongshen He ◽  
Roman Boehringer ◽  
Arthur J.Y. Huang ◽  
Eric T.N. Overton ◽  
Denis Polygalov ◽  
...  
Keyword(s):  
Pyramidal Cell ◽  
Crucial Role ◽  
Pyramidal Cells ◽  
Population Activity ◽  
Ca1 Neurons ◽  
Neuronal Ensembles ◽  
Sharp Wave

AbstractThe structured reactivation of hippocampal neuronal ensembles during fast synchronous oscillatory events termed sharp-wave ripples (SWRs) has been suggested to play a crucial role in the storage and use of memory. Activity in both the CA2 and CA3 subregions can proceed this population activity in CA1 and chronic inhibition of either region alters SWR oscillations. However, the precise contribution of CA2 to the oscillation, as well as to the reactivation of CA1 neurons within it, remains unclear. Here we employ chemogenetics to transiently silence CA2 pyramidal cells in mice and observe that while SWRs still occur, the reactivation of CA1 pyramidal cell ensembles within the events lose both temporal and informational precision. These observations suggest that CA2 activity contributes to the fidelity of experience-dependent hippocampal replay.

scholarly journals Impaired spike-gamma coupling of area CA3 fast-spiking interneurons as the earliest functional impairment in the AppNL-G-F mouse model of Alzheimer’s disease

2021 ◽  
Author(s):  
Luis Enrique Arroyo-García ◽  
Arturo G. Isla ◽  
Yuniesky Andrade-Talavera ◽  
Hugo Balleza-Tapia ◽  
Raúl Loera-Valencia ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mouse Model ◽  
Functional Impairment ◽  
Amyloid Β ◽  
Gamma Oscillations ◽  
Gamma Oscillation ◽  
Gamma Rhythm ◽  
Fast Spiking

AbstractIn Alzheimer’s disease (AD) the accumulation of amyloid-β (Aβ) correlates with degradation of cognition-relevant gamma oscillations. The gamma rhythm relies on proper neuronal spike-gamma coupling, specifically of fast-spiking interneurons (FSN). Here we tested the hypothesis that decrease in gamma power and FSN synchrony precede amyloid plaque deposition and cognitive impairment in AppNL-G-F knock-in mice (AppNL-G-F). The aim of the study was to evaluate the amyloidogenic pathology progression in the novel AppNL-G-F mouse model using in vitro electrophysiological network analysis. Using patch clamp of FSNs and pyramidal cells (PCs) with simultaneous gamma oscillation recordings, we compared the activity of the hippocampal network of wild-type mice (WT) and the AppNL-G-F mice at four disease stages (1, 2, 4, and 6 months of age). We found a severe degradation of gamma oscillation power that is independent of, and precedes Aβ plaque formation, and the cognitive impairment reported previously in this animal model. The degradation correlates with increased Aβ1-42 concentration in the brain. Analysis on the cellular level showed an impaired spike-gamma coupling of FSN from 2 months of age that correlates with the degradation of gamma oscillations. From 6 months of age PC firing becomes desynchronized also, correlating with reports in the literature of robust Aβ plaque pathology and cognitive impairment in the AppNL-G-F mice. This study provides evidence that impaired FSN spike-gamma coupling is one of the earliest functional impairment caused by the amyloidogenic pathology progression likely is the main cause for the degradation of gamma oscillations and consequent cognitive impairment. Our data suggests that therapeutic approaches should be aimed at restoring normal FSN spike-gamma coupling and not just removal of Aβ.

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