scholarly journals Chronic in vivo optogenetic stimulation modulates neuronal excitability, spine morphology, and Hebbian plasticity in the mouse hippocampus

Hippocampus ◽  
2019 ◽  
Vol 29 (8) ◽  
pp. 755-761 ◽  
Author(s):  
Thiago C. Moulin ◽  
Lyvia L. Petiz ◽  
Danielle Rayêe ◽  
Jessica Winne ◽  
Roberto G. Maia ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Spine Morphology ◽  
Optogenetic Stimulation ◽  
Hebbian Plasticity ◽  
Mouse Hippocampus

scholarly journals Chronic in vivo optogenetic stimulation modulates neuronal excitability, spine morphology and Hebbian plasticity in the mouse hippocampus

2018 ◽  
Author(s):  
Thiago C. Moulin ◽  
Lyvia L. Petiz ◽  
Danielle Rayêe ◽  
Jessica Winne ◽  
Roberto G. Maia ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Ex Vivo ◽  
Morphological Changes ◽  
Spine Density ◽  
Optogenetic Stimulation ◽  
Light Pulses ◽  
Ca1 Region ◽  
Hebbian Plasticity

AbstractProlonged increases in excitation can trigger cell-wide homeostatic responses in neurons, altering membrane channels, promoting morphological changes and ultimately reducing synaptic weights. However, how synaptic downscaling interacts with classical forms of Hebbian plasticity is still unclear. In this study, we investigated whether chronic optogenetic stimulation of hippocampus CA1 pyramidal neurons in freely-moving mice could (a) cause morphological changes reminiscent of homeostatic scaling, (b) modulate synaptic currents that might compensate for chronic excitation, and (c) lead to alterations in Hebbian plasticity. After 24 h of stimulation with 15-ms blue light pulses every 90 s, dendritic spine density and area were reduced in the CA1 region of mice expressing channelrhodopsin-2 (ChR2) when compared to controls. This protocol also reduced the amplitude of mEPSCs for both the AMPA and NMDA components in ex vivo slices obtained from ChR2-expressing mice immediately after the end of stimulation. Lastly, chronic stimulation impaired the induction of LTP and facilitated that of LTD in these slices. Our results indicate that neuronal responses to prolonged network excitation can modulate subsequent Hebbian plasticity in the hippocampus.

scholarly journals BDNF-induced TrkB activation down-regulates the K+–Cl− cotransporter KCC2 and impairs neuronal Cl− extrusion

2002 ◽  
Vol 159 (5) ◽  
pp. 747-752 ◽  
Author(s):  
Claudio Rivera ◽  
Hong Li ◽  
Judith Thomas-Crusells ◽  
Hannele Lahtinen ◽  
Tero Viitanen ◽  
...  
Keyword(s):  
Hippocampal Slice ◽  
Neuronal Excitability ◽  
Epileptic Activity ◽  
Signaling Cascades ◽  
Gabaergic Inhibition ◽  
Long Term Effects ◽  
Mouse Hippocampus

Pathophysiological activity and various kinds of traumatic insults are known to have deleterious long-term effects on neuronal Cl− regulation, which can lead to a suppression of fast postsynaptic GABAergic responses. Brain-derived neurotrophic factor (BDNF) increases neuronal excitability through a conjunction of mechanisms that include regulation of the efficacy of GABAergic transmission. Here, we show that exposure of rat hippocampal slice cultures and acute slices to exogenous BDNF or neurotrophin-4 produces a TrkB-mediated fall in the neuron-specific K+–Cl− cotransporter KCC2 mRNA and protein, as well as a consequent impairment in neuronal Cl− extrusion capacity. After kindling-induced seizures in vivo, the expression of KCC2 is down-regulated in the mouse hippocampus with a spatiotemporal profile complementary to the up-regulation of TrkB and BDNF. The present data demonstrate a novel mechanism whereby BDNF/TrkB signaling suppresses chloride-dependent fast GABAergic inhibition, which most likely contributes to the well-known role of TrkB-activated signaling cascades in the induction and establishment of epileptic activity.

Implantable neural interfaces

2018 ◽  
Author(s):  
Stefano Vassanelli
Keyword(s):  
Brain Function ◽  
Large Scale ◽  
Ionic Channels ◽  
Patch Clamp Technique ◽  
Advantages And Disadvantages ◽  
Optogenetic Stimulation ◽  
Physical Interfaces ◽  
The Brain

Establishing direct communication with the brain through physical interfaces is a fundamental strategy to investigate brain function. Starting with the patch-clamp technique in the seventies, neuroscience has moved from detailed characterization of ionic channels to the analysis of single neurons and, more recently, microcircuits in brain neuronal networks. Development of new biohybrid probes with electrodes for recording and stimulating neurons in the living animal is a natural consequence of this trend. The recent introduction of optogenetic stimulation and advanced high-resolution large-scale electrical recording approaches demonstrates this need. Brain implants for real-time neurophysiology are also opening new avenues for neuroprosthetics to restore brain function after injury or in neurological disorders. This chapter provides an overview on existing and emergent neurophysiology technologies with particular focus on those intended to interface neuronal microcircuits in vivo. Chemical, electrical, and optogenetic-based interfaces are presented, with an analysis of advantages and disadvantages of the different technical approaches.

scholarly journals Selective Viral Transduction of Adult-born Olfactory Neurons for Chronic in vivo Optogenetic Stimulation

10.3791/3380 ◽  
2011 ◽  
Author(s):  
Gabriel Lepousez ◽  
Mariana Alonso ◽  
Sebastian Wagner ◽  
Benjamin W. Gallarda ◽  
Pierre-Marie Lledo
Keyword(s):  
Olfactory Neurons ◽  
Optogenetic Stimulation ◽  
Viral Transduction

Toward heterogeneity in feedforward network with synaptic delays based on FitzHugh–Nagumo model

2018 ◽  
Vol 32 (01) ◽  
pp. 1750274 ◽  
Author(s):  
Ying-Mei Qin ◽  
Cong Men ◽  
Jia Zhao ◽  
Chun-Xiao Han ◽  
Yan-Qiu Che
Keyword(s):  
Neuronal Excitability ◽  
Temporal Coding ◽  
Feedforward Network ◽  
Firing Patterns ◽  
In Vivo Experiments ◽  
Connection Probability ◽  
Rate Coding

We focus on the role of heterogeneity on the propagation of firing patterns in feedforward network (FFN). Effects of heterogeneities both in parameters of neuronal excitability and synaptic delays are investigated systematically. Neuronal heterogeneity is found to modulate firing rates and spiking regularity by changing the excitability of the network. Synaptic delays are strongly related with desynchronized and synchronized firing patterns of the FFN, which indicate that synaptic delays may play a significant role in bridging rate coding and temporal coding. Furthermore, quasi-coherence resonance (quasi-CR) phenomenon is observed in the parameter domain of connection probability and delay-heterogeneity. All these phenomena above enable a detailed characterization of neuronal heterogeneity in FFN, which may play an indispensable role in reproducing the important properties of in vivo experiments.

scholarly journals Rem2 stabilizes intrinsic excitability and spontaneous firing in visual circuits

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Anna R Moore ◽  
Sarah E Richards ◽  
Katelyn Kenny ◽  
Leandro Royer ◽  
Urann Chan ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Ocular Dominance ◽  
Sensory Experience ◽  
Cellular Level ◽  
Synaptic Function ◽  
Intrinsic Excitability ◽  
Spontaneous Firing ◽  
Circuit Function

Sensory experience plays an important role in shaping neural circuitry by affecting the synaptic connectivity and intrinsic properties of individual neurons. Identifying the molecular players responsible for converting external stimuli into altered neuronal output remains a crucial step in understanding experience-dependent plasticity and circuit function. Here, we investigate the role of the activity-regulated, non-canonical Ras-like GTPase Rem2 in visual circuit plasticity. We demonstrate that Rem2-/- mice fail to exhibit normal ocular dominance plasticity during the critical period. At the cellular level, our data establish a cell-autonomous role for Rem2 in regulating intrinsic excitability of layer 2/3 pyramidal neurons, prior to changes in synaptic function. Consistent with these findings, both in vitro and in vivo recordings reveal increased spontaneous firing rates in the absence of Rem2. Taken together, our data demonstrate that Rem2 is a key molecule that regulates neuronal excitability and circuit function in the context of changing sensory experience.

scholarly journals Non-synaptic Cell-Autonomous Mechanisms Underlie Neuronal Hyperactivity in a Genetic Model of PIK3CA-Driven Intractable Epilepsy

2021 ◽  
Vol 14 ◽  
Author(s):  
Achira Roy ◽  
Victor Z. Han ◽  
Angela M. Bard ◽  
Devin T. Wehle ◽  
Stephen E. P. Smith ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Genetic Model ◽  
Ex Vivo ◽  
Significant Proportion ◽  
Intractable Epilepsy ◽  
Therapeutic Interventions ◽  
Hippocampal Pyramidal Neurons ◽  
Phosphoinositide 3 Kinase

Patients harboring mutations in the PI3K-AKT-MTOR pathway-encoding genes often develop a spectrum of neurodevelopmental disorders including epilepsy. A significant proportion remains unresponsive to conventional anti-seizure medications. Understanding mutation-specific pathophysiology is thus critical for molecularly targeted therapies. We previously determined that mouse models expressing a patient-related activating mutation in PIK3CA, encoding the p110α catalytic subunit of phosphoinositide-3-kinase (PI3K), are epileptic and acutely treatable by PI3K inhibition, irrespective of dysmorphology. Here we report the physiological mechanisms underlying this dysregulated neuronal excitability. In vivo, we demonstrate epileptiform events in the Pik3ca mutant hippocampus. By ex vivo analyses, we show that Pik3ca-driven hyperactivation of hippocampal pyramidal neurons is mediated by changes in multiple non-synaptic, cell-intrinsic properties. Finally, we report that acute inhibition of PI3K or AKT, but not MTOR activity, suppresses the intrinsic hyperactivity of the mutant neurons. These acute mechanisms are distinct from those causing neuronal hyperactivity in other AKT-MTOR epileptic models and define parameters to facilitate the development of new molecularly rational therapeutic interventions for intractable epilepsy.

scholarly journals Flexible and stretchable polymer optical fibers for chronic brain and vagus nerve optogenetic stimulations in free-behaving animals

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yi Cao ◽  
Suwan Pan ◽  
Mengying Yan ◽  
Chongyang Sun ◽  
Jianyu Huang ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Optical Fibers ◽  
Primary Motor Cortex ◽  
Inhibitory Influence ◽  
Therapeutic Effects ◽  
Nervous Systems ◽  
Optogenetic Stimulation ◽  
Neuropsychiatric Diseases ◽  
Polymer Optical Fibers

Abstract Background Although electrical stimulation of the peripheral and central nervous systems has attracted much attention owing to its potential therapeutic effects on neuropsychiatric diseases, its non-cell-type-specific activation characteristics may hinder its wide clinical application. Unlike electrical methodologies, optogenetics has more recently been applied as a cell-specific approach for precise modulation of neural functions in vivo, for instance on the vagus nerve. The commonly used implantable optical waveguides are silica optical fibers, which for brain optogenetic stimulation (BOS) are usually fixed on the skull bone. However, due to the huge mismatch of mechanical properties between the stiff optical implants and deformable vagal tissues, vagus nerve optogenetic stimulation (VNOS) in free-behaving animals continues to be a great challenge. Results To resolve this issue, we developed a simplified method for the fabrication of flexible and stretchable polymer optical fibers (POFs), which show significantly improved characteristics for in vivo optogenetic applications, specifically a low Young’s modulus, high stretchability, improved biocompatibility, and long-term stability. We implanted the POFs into the primary motor cortex of C57 mice after the expression of CaMKIIα-ChR2-mCherry detected frequency-dependent neuronal activity and the behavioral changes during light delivery. The viability of POFs as implantable waveguides for VNOS was verified by the increased firing rate of the fast-spiking GABAergic interneurons recorded in the left vagus nerve of VGAT-ChR2 transgenic mice. Furthermore, VNOS was carried out in free-moving rodents via chronically implanted POFs, and an inhibitory influence on the cardiac system and an anxiolytic effect on behaviors was shown. Conclusion Our results demonstrate the feasibility and advantages of the use of POFs in chronic optogenetic modulations in both of the central and peripheral nervous systems, providing new information for the development of novel therapeutic strategies for the treatment of neuropsychiatric disorders.

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