scholarly journals Ketamine anesthesia induces gain enhancement via recurrent excitation in granular input layers of the auditory cortex

2019 ◽  
Author(s):  
Katrina E. Deane ◽  
Michael G. K. Brunk ◽  
Andrew W. Curran ◽  
Marina M. Zempeltzi ◽  
Jing Ma ◽  
...  
Keyword(s):  
Auditory Cortex ◽  
Network Activity ◽  
Anesthetic Agent ◽  
Clinical Effects ◽  
Gabaergic Interneurons ◽  
Mongolian Gerbils ◽  
Gain Enhancement ◽  
Recurrent Excitation ◽  
Input Processing ◽  
Granular Layers

The N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, is commonly used as an anesthetic agent and has more recently gained attention as an antidepressant. Ketamine has been linked to increased stimulus-locked excitability, inhibition of interneurons, and modulation of intrinsic neuronal oscillations. However, the functional network mechanisms are still elusive. A better understanding of these anesthetic network effects may improve upon previous interpretations of seminal studies conducted under anesthesia and have widespread relevance for neuroscience with awake and anesthetized subjects as well as in medicine. Here, we investigated the effects of anesthetic doses of ketamine (15mg kg−1/h i.p.) on the network activity after pure tone stimulation within the auditory cortex of male Mongolian gerbils (Meriones unguiculatus). We used laminar current source density (CSD) analysis and subsequent layer-specific continuous wavelet analysis to investigate spatiotemporal response dynamics on cortical columnar processing in awake and ketamine-anesthetized animals. We found thalamocortical input processing within granular layers III/IV to be significantly increased under ketamine. This effect on early thalamocortical input processing was not due to changes in cross-trial phase coherence. Rather, the layer-dependent gain enhancement under ketamine was attributed to a broadband increase in amplitude reflecting an increase in recurrent excitation. The time-frequency analysis is further indicative of a prolonged period of stimulus-induced excitation possibly due to a reduced coupling of excitation and inhibition in granular input circuits—in line with the common hypothesis of cortical disinhibition via NMDA-mediated suppression of GABAergic interneurons.Statement of significanceKetamine is a common anesthetic agent and is known to alter excitability and neuronal synchronicity in the cortex. We reveal here that anesthetic doses of ketamine increase recurrent excitation of thalamic input in the granular layers of the auditory cortex of Mongolian gerbils. This leads to a layer-specific gain enhancement of the time-locked response to external stimuli. Analysis of tone-evoked amplitudes and cross-trial variability of cortical current sources and sinks indicate a mechanism of cortical disinhibition via NMDA-mediated suppression of GABAergic interneurons. Our findings might help to understand the functional mechanisms of the clinical effects of ketamine promoting the development of new therapeutic agents with lower side effects.

scholarly journals Layer-Specific Intracortical Amplification Shortens the Lifetime of Thalamocortical Repetition Suppression in Auditory Cortex

2021 ◽  
Author(s):  
Jing Ma ◽  
Michael Brunk ◽  
Artur Matysiak ◽  
Nina Härtwich ◽  
Frank Ohl ◽  
...  
Keyword(s):  
Auditory Cortex ◽  
Current Source ◽  
Primary Auditory Cortex ◽  
Meriones Unguiculatus ◽  
Neural Adaptation ◽  
Fundamental Aspect ◽  
Mongolian Gerbils ◽  
Cortical Layers ◽  
Repetition Suppression ◽  
Granular Layers

Abstract Neural adaptation in sensory cortex serves important sensory functions, and is altered by various neurophsychiatric diseases. Although adaptation is a widely studied phenomenon, much remains unknown about its underlying mechanisms on a cortical circuit level. Here, we investigated repetition suppression as fundamental aspect of adaptation by layer-specific current source density analyses of synaptic mass activities in primary auditory cortex of anesthetized Mongolian gerbils (Meriones unguiculatus). We disentangled different synaptic contributions to repetition suppression in different cortical layers, and separated thalamocortical from intracortical inputs by cortical silencing with GABAA-agonist muscimol. We systematically varied stimulus onset intervals and employed statistically robust model fitting based on bootstrapping to determine the full suppression kinetics of different synaptic responses in the steady state. Whereas thalamocortical input to granular and infragranular layers was governed by longer lasting repetition suppression, most likely reflecting depression of thalamocortical synapses, intracortical amplification in granular layers shortened the lifetime of suppression by re-enhancing granular responses mainly through synchronization of synaptic events. With increasing latency, the shorter lasting suppression kinetics observed in granular layers at early latencies (<100ms) passed on to deeper layers replacing the longer lasting infragranular suppression kinetics. Granular circuit dynamics can therefore actively shape neural adaptation across cortical layers.

scholarly journals Ketamine anaesthesia induces gain enhancement via recurrent excitation in granular input layers of the auditory cortex

2020 ◽  
Vol 598 (13) ◽  
pp. 2741-2755 ◽  
Author(s):  
Katrina E. Deane ◽  
Michael G. K. Brunk ◽  
Andrew W. Curran ◽  
Marina M. Zempeltzi ◽  
Jing Ma ◽  
...  
Keyword(s):  
Auditory Cortex ◽  
Gain Enhancement ◽  
Ketamine Anaesthesia ◽  
Recurrent Excitation

Endocannabinoid system in the neurodevelopment of GABAergic interneurons: implications for neurological and psychiatric disorders

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Chang-geng Song ◽  
Xin Kang ◽  
Fang Yang ◽  
Wan-qing Du ◽  
Jia-jia Zhang ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Endocannabinoid System ◽  
Autism Spectrum ◽  
Network Activity ◽  
Inhibitory Neurons ◽  
Gabaergic Interneurons ◽  
Neural Stem Progenitor Cells ◽  
The Central Nervous System ◽  
Interneuron Development

Abstract In mature mammalian brains, the endocannabinoid system (ECS) plays an important role in the regulation of synaptic plasticity and the functioning of neural networks. Besides, the ECS also contributes to the neurodevelopment of the central nervous system. Due to the increase in the medical and recreational use of cannabis, it is inevitable and essential to elaborate the roles of the ECS on neurodevelopment. GABAergic interneurons represent a group of inhibitory neurons that are vital in controlling neural network activity. However, the role of the ECS in the neurodevelopment of GABAergic interneurons remains to be fully elucidated. In this review, we provide a brief introduction of the ECS and interneuron diversity. We focus on the process of interneuron development and the role of ECS in the modulation of interneuron development, from the expansion of the neural stem/progenitor cells to the migration, specification and maturation of interneurons. We further discuss the potential implications of the ECS and interneurons in the pathogenesis of neurological and psychiatric disorders, including epilepsy, schizophrenia, major depressive disorder and autism spectrum disorder.

Relationship between GABAergic interneurons migration and early neocortical network activity

2009 ◽  
Vol 69 (2-3) ◽  
pp. 105-123 ◽  
Author(s):  
Ana D. de Lima ◽  
Anne Gieseler ◽  
Thomas Voigt
Keyword(s):  
Network Activity ◽  
Gabaergic Interneurons ◽  
Neocortical Network

scholarly journals Mechanisms underlying the response of mouse cortical networks to optogenetic manipulation

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Alexandre Mahrach ◽  
Guang Chen ◽  
Nuo Li ◽  
Carl van Vreeswijk ◽  
David Hansel
Keyword(s):  
Motor Cortex ◽  
Numerical Simulations ◽  
Barrel Cortex ◽  
Population Models ◽  
Gabaergic Interneurons ◽  
Paradoxical Effect ◽  
Form Complex ◽  
Recurrent Excitation ◽  
Layer 2

GABAergic interneurons can be subdivided into three subclasses: parvalbumin positive (PV), somatostatin positive (SOM) and serotonin positive neurons. With principal cells (PCs) they form complex networks. We examine PCs and PV responses in mouse anterior lateral motor cortex (ALM) and barrel cortex (S1) upon PV photostimulation in vivo. In ALM layer five and S1, the PV response is paradoxical: photoexcitation reduces their activity. This is not the case in ALM layer 2/3. We combine analytical calculations and numerical simulations to investigate how these results constrain the architecture. Two-population models cannot explain the results. Four-population networks with V1-like architecture account for the data in ALM layer 2/3 and layer 5. Our data in S1 can be explained if SOM neurons receive inputs only from PCs and PV neurons. In both four-population models, the paradoxical effect implies not too strong recurrent excitation. It is not evidence for stabilization by inhibition.

scholarly journals State Transitions During Discrimination Learning in the Gerbil Auditory Cortex Analyzed by Network Causality Metrics

2021 ◽  
Vol 15 ◽  
Author(s):  
Robert Kozma ◽  
Sanqing Hu ◽  
Yury Sokolov ◽  
Tim Wanger ◽  
Andreas L. Schulz ◽  
...  
Keyword(s):  
Auditory Cortex ◽  
Discrimination Learning ◽  
Structural Changes ◽  
State Transitions ◽  
Cognitive State ◽  
Mongolian Gerbils ◽  
Electrode Arrays ◽  
Network Graph ◽  
Cortical Networks ◽  
Avoidance Strategy

This work studies the evolution of cortical networks during the transition from escape strategy to avoidance strategy in auditory discrimination learning in Mongolian gerbils trained by the well-established two-way active avoidance learning paradigm. The animals were implanted with electrode arrays centered on the surface of the primary auditory cortex and electrocorticogram (ECoG) recordings were made during performance of an auditory Go/NoGo discrimination task. Our experiments confirm previous results on a sudden behavioral change from the initial naïve state to an avoidance strategy as learning progresses. We employed two causality metrics using Granger Causality (GC) and New Causality (NC) to quantify changes in the causality flow between ECoG channels as the animals switched to avoidance strategy. We found that the number of channel pairs with inverse causal interaction significantly increased after the animal acquired successful discrimination, which indicates structural changes in the cortical networks as a result of learning. A suitable graph-theoretical model is developed to interpret the findings in terms of cortical networks evolving during cognitive state transitions. Structural changes lead to changes in the dynamics of neural populations, which are described as phase transitions in the network graph model with small-world connections. Overall, our findings underscore the importance of functional reorganization in sensory cortical areas as a possible neural contributor to behavioral changes.

scholarly journals Optogenetic stimulation of the VTA modulates a frequency-specific gain of thalamocortical inputs in infragranular layers of the auditory cortex

2019 ◽  
Author(s):  
Michael G. K. Brunk ◽  
Katrina E. Deane ◽  
Martin Kisse ◽  
Matthias Deliano ◽  
Silvia Vieweg ◽  
...  
Keyword(s):  
Auditory Cortex ◽  
Information Transfer ◽  
Cortical Plasticity ◽  
Current Source ◽  
Primary Auditory Cortex ◽  
Mongolian Gerbils ◽  
Spectral Processing ◽  
Optogenetic Stimulation ◽  
Spectral Integration ◽  
Stimulation Of

AbstractBackgroundReward associations during auditory learning induce cortical plasticity in the primary auditory cortex. A prominent source of such influence is the ventral tegmental area (VTA), which conveys a dopaminergic teaching signal to the primary auditory cortex. It is currently unknown, however, how the VTA circuitry thereby influences cortical frequency information processing and spectral integration. In this study, we therefore investigated the temporal effects of direct optogenetic stimulation of the VTA onto spectral integration in the auditory cortex on a synaptic circuit level by current-source-density analysis in anesthetized Mongolian gerbils.ResultsWhile auditory lemniscal input predominantly terminates in the granular input layers III/IV, we found that VTA-mediated modulation of spectral processing is relayed by a different circuit, namely enhanced thalamic inputs to the infragranular layers Vb/VIa. Activation of this circuit yields a frequency-specific gain amplification of local sensory input and enhances corticocortical information transfer, especially in supragranular layers I/II. This effects further persisted over more than 30 minutes after VTA stimulation.ConclusionsAltogether, we demonstrate that the VTA exhibits a long-lasting influence on sensory cortical processing via infragranular layers transcending the signaling of a mere reward-prediction error. Our findings thereby demonstrate a cellular and circuit substrate for the influence of reinforcement-evaluating brain systems on sensory processing in the auditory cortex.

scholarly journals A synaptic threshold mechanism for computing escape decisions

2018 ◽  
Author(s):  
D.A Evans ◽  
A.V. Stempel ◽  
R. Vale ◽  
S. Ruehle ◽  
Y. Lefler ◽  
...  
Keyword(s):  
Network Activity ◽  
Biophysical Model ◽  
Sensory Stimuli ◽  
Recurrent Excitation ◽  
Threshold Mechanism ◽  
Threat Level ◽  
Deep Layers ◽  
Defensive Behaviours ◽  
And Control ◽  
The Brain

Escaping from imminent danger is an instinctive behaviour fundamental for survival that requires classifying sensory stimuli as harmless or threatening. The absence of threat allows animals to forage for essential resources, but as the level of threat and potential for harm increases, they have to decide whether or not to seek safety1. Despite previous work on instinctive defensive behaviours in rodents2–13, little is known about how the brain computes the threat level for initiating escape. Here we show that the probability and vigour of escape in mice scale with the intensity of innate threats, and are well described by a theoretical model that computes the distance between threat level and an escape threshold. Calcium imaging and optogenetics in the midbrain of freely behaving mice show that the activity of excitatory VGluT2+ neurons in the deep layers of the medial superior colliculus (mSC) represents the threat stimulus intensity and is predictive of escape, whereas dorsal periaqueductal gray (dPAG) VGluT2+ neurons encode exclusively the escape choice and control escape vigour. We demonstrate a feed-forward monosynaptic excitatory connection from mSC to dPAG neurons that is weak and unreliable, yet necessary for escape behaviour, and which we suggest provides a synaptic threshold for dPAG activation and the initiation of escape. This threshold can be overcome by high mSC network activity because of short-term synaptic facilitation and recurrent excitation within the mSC, which amplifies and sustains synaptic drive to the dPAG. Thus, dPAG VGluT2+ neurons compute escape decisions and vigour using a synaptic mechanism to threshold threat information received from the mSC, and provide a biophysical model of how the brain performs a critical behavioural computation.

scholarly journals GABAergic interneurons excite neonatal hippocampus in vivo

2020 ◽  
Vol 6 (24) ◽  
pp. eaba1430 ◽  
Author(s):  
Yasunobu Murata ◽  
Matthew T. Colonnese
Keyword(s):  
Visual Cortex ◽  
Synapse Formation ◽  
Reversal Potential ◽  
Pyramidal Cells ◽  
Gabaergic Neurons ◽  
Network Activity ◽  
Gabaergic Interneuron ◽  
Gabaergic Interneurons ◽  
Early Postnatal Development

GABAergic interneurons are proposed to be critical for early activity and synapse formation by directly exciting, rather than inhibiting, neurons in developing hippocampus and neocortex. However, the role of GABAergic neurons in the generation of neonatal network activity has not been tested in vivo, and recent studies have challenged the excitatory nature of early GABA. By locally manipulating interneuron activity in unanesthetized neonatal mice, we show that GABAergic neurons are excitatory in CA1 hippocampus at postnatal day 3 (P3) and are responsible for most of the spontaneous firing of pyramidal cells at that age. Hippocampal interneurons become inhibitory by P7, whereas visual cortex interneurons are already inhibitory by P3 and remain so throughout development. These regional and age-specific differences are the result of a change in chloride reversal potential, because direct activation of light-gated anion channels in glutamatergic neurons drives CA1 firing at P3, but silences it at P7 in CA1, and at all ages in visual cortex. This study in the intact brain reveals that GABAergic interneuron excitation is essential for network activity in neonatal hippocampus and confirms that visual cortical interneurons are inhibitory throughout early postnatal development.

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