scholarly journals Synaptic Zinc Enhances Inhibition Mediated by Somatostatin, but not Parvalbumin, Cells in Mouse Auditory Cortex

2020 ◽  
Vol 30 (7) ◽  
pp. 3895-3909
Author(s):  
Stylianos Kouvaros ◽  
Manoj Kumar ◽  
Thanos Tzounopoulos
Keyword(s):  
Auditory Cortex ◽  
Sensory Processing ◽  
Frequency Tuning ◽  
Brain Activity ◽  
Brain Slices ◽  
Cortical Inhibition ◽  
Gabaergic Neurotransmission ◽  
Quantal Size ◽  
And Behavior

Abstract Cortical inhibition is essential for brain activity and behavior. Yet, the mechanisms that modulate cortical inhibition and their impact on sensory processing remain less understood. Synaptically released zinc, a neuromodulator released by cortical glutamatergic synaptic vesicles, has emerged as a powerful modulator of sensory processing and behavior. Despite the puzzling finding that the vesicular zinc transporter (ZnT3) mRNA is expressed in cortical inhibitory interneurons, the actions of synaptic zinc in cortical inhibitory neurotransmission remain unknown. Using in vitro electrophysiology and optogenetics in mouse brain slices containing the layer 2/3 (L2/3) of auditory cortex, we discovered that synaptic zinc increases the quantal size of inhibitory GABAergic neurotransmission mediated by somatostatin (SOM)- but not parvalbumin (PV)-expressing neurons. Using two-photon imaging in awake mice, we showed that synaptic zinc is required for the effects of SOM- but not PV-mediated inhibition on frequency tuning of principal neurons. Thus, cell-specific zinc modulation of cortical inhibition regulates frequency tuning.

Insulin-like growth factor 1 (IGF-1) increases GABAergic neurotransmission to GnRH neurons via suppressing the retrograde tonic endocannabinoid signaling pathway in mice

2020 ◽  
Author(s):  
Flora Balint ◽  
Veronika Csillag ◽  
Csaba Vastagh ◽  
Zsolt Liposits ◽  
Imre Farkas
Keyword(s):  
Growth Factor ◽  
Transient Receptor Potential ◽  
Brain Slices ◽  
Fine Tuning ◽  
Transient Receptor Potential Vanilloid ◽  
Insulin Like Growth Factor ◽  
Gabaergic Neurotransmission ◽  
Postsynaptic Currents ◽  
Gnrh Neurons

Introduction: Hypophysiotropic gonadotropin releasing-hormone (GnRH) neurons orchestrate various physiological events that control the onset of puberty. Previous studies showed that insulin-like growth factor 1 (IGF-1) induces the secretion of GnRH and accelerates the onset of puberty, suggesting a regulatory role of this hormone upon GnRH neurons. Methods: To reveal responsiveness of GnRH neurons to IGF-1 and elucidate molecular pathways acting downstream to the IGF-1 receptor (IGF-1R), in vitro electrophysiological experiments were carried out on GnRH-GFP neurons in acute brain slices from prepubertal (23-29 days) and pubertal (50-day) male mice. Results: Administration of IGF-1 (13 nM) significantly increased the firing rate and frequency of spontaneous postsynaptic currents (sPSCs), and that of excitatory GABAergic miniature postsynaptic currents (mPSCs). No GABAergic mPSCs were induced by IGF-1 in the presence of GABAA-R blocker picrotoxin. The increase in the mPSC frequency was prevented by the use of IGF-1R antagonist, JB1 (1 µM) or the intracellularly applied PI3K blocker (LY294002, 50 µM) showing involvement of IGF-1R and PI3K in the mechanism. Blockade of the transient receptor potential vanilloid 1 (TRPV1), an element of the tonic retrograde endocannabinoid machinery by AMG9810 (10 µM) or antagonizing cannabinoid receptor type-1 (CB1) by AM251 (1 µM) abolished the effect. Discussion/Conclusion: These findings indicate that IGF-1 arrests the tonic retrograde endocannabinoid pathway in GnRH neurons and this disinhibition increases the release of GABA from presynaptic terminals that, in turn, activates GnRH neurons leading to the fine-tuning of the hypothalamo-pituitary-gonadal axis.

scholarly journals Closed-loop optogenetic control of normal and pathological network dynamics

2020 ◽  
Author(s):  
Boubker Zaaimi ◽  
Mark Turnbull ◽  
Anupam Hazra ◽  
Yujiang Wang ◽  
Carolina Gandara de Souza ◽  
...  
Keyword(s):  
Closed Loop ◽  
Brain Activity ◽  
Nonlinear Dynamical System ◽  
Brain Slices ◽  
Open Loop ◽  
Loop Control ◽  
Nonlinear Dynamical ◽  
Light Emitting

Abstract Electrical neurostimulation is effective in treating neurological disorders, but associated recording artefacts generally limit applications to ‘open-loop’ stimuli. Since light does not prevent concurrent electrical recordings, optogenetics enables real-time, continuous ‘closed-loop’ control of brain activity. Here we show that closed-loop optogenetic stimulation with excitatory opsins (CLOSe) affords precise manipulation of neural dynamics, both in vitro, in brain slices from transgenic mice, and in vivo, with anesthetised monkeys. We demonstrate the generation of oscillations in quiescent tissue, enhancement or suppression of endogenous patterns in active tissue, and modulation of seizure-like bursts elicited by 4-aminopyridine. New network properties, emergent under CLOSe, depended on the phase-shift imposed between neural activity and optical stimulation, and could be modelled with a nonlinear dynamical system. In particular, CLOSe could stabilise or destabilise limit cycles associated with seizure oscillations, evident from systematic changes in the variability and entropy of seizure trajectories that correlated with their altered duration and intensity. Furthermore, CLOSe was achieved using intracortical optrodes incorporating light-emitting diodes, paving the way for translation of closed-loop optogenetics towards therapeutic applications in humans.

scholarly journals Characterization of thalamocortical responses of regular-spiking and fast-spiking neurons of the mouse auditory cortex in vitro and in silico

2012 ◽  
Vol 107 (5) ◽  
pp. 1476-1488 ◽  
Author(s):  
Max L. Schiff ◽  
Alex D. Reyes
Keyword(s):  
Auditory Cortex ◽  
Pyramidal Neurons ◽  
Modulation Frequency ◽  
Primary Auditory Cortex ◽  
Cortical Inhibition ◽  
Membrane Properties ◽  
Thalamic Stimulation ◽  
Fast Spiking

We use a combination of in vitro whole cell recordings and computer simulations to characterize the cellular and synaptic properties that contribute to processing of auditory stimuli. Using a mouse thalamocortical slice preparation, we record the intrinsic membrane properties and synaptic properties of layer 3/4 regular-spiking (RS) pyramidal neurons and fast-spiking (FS) interneurons in primary auditory cortex (AI). We find that postsynaptic potentials (PSPs) evoked in FS cells are significantly larger and depress more than those evoked in RS cells after thalamic stimulation. We use these data to construct a simple computational model of the auditory thalamocortical circuit and find that the differences between FS and RS cells observed in vitro generate model behavior similar to that observed in vivo. We examine how feedforward inhibition and synaptic depression affect cortical responses to time-varying inputs that mimic sinusoidal amplitude-modulated tones. In the model, the balance of cortical inhibition and thalamic excitation evolves in a manner that depends on modulation frequency (MF) of the stimulus and determines cortical response tuning.

scholarly journals A Critical Role of Inhibition in Temporal Processing Maturation in the Primary Auditory Cortex

2017 ◽  
Vol 28 (5) ◽  
pp. 1610-1624 ◽  
Author(s):  
Dongqin Cai ◽  
Rongrong Han ◽  
Miaomiao Liu ◽  
Fenghua Xie ◽  
Ling You ◽  
...  
Keyword(s):  
Auditory Cortex ◽  
Temporal Processing ◽  
Critical Role ◽  
Primary Auditory Cortex ◽  
Cortical Inhibition ◽  
Fast Spiking ◽  
Processing Mechanisms

Abstract Faithful representation of sound envelopes in primary auditory cortex (A1) is vital for temporal processing and perception of natural sounds. However, the emergence of cortical temporal processing mechanisms during development remains poorly understood. Although cortical inhibition has been proposed to play an important role in this process, direct in-vivo evidence has been lacking. Using loose-patch recordings in rat A1 immediately after hearing onset, we found that stimulus-following ability in fast-spiking neurons was significantly better than in regular-spiking (RS) neurons. In-vivo whole-cell recordings of RS neurons revealed that inhibition in the developing A1 demonstrated much weaker adaptation to repetitive stimuli than in adult A1. Furthermore, inhibitory synaptic inputs were of longer duration than observed in vitro and in adults. Early in development, overlap of the prolonged inhibition evoked by 2 closely following stimuli disrupted the classical temporal sequence between excitation and inhibition, resulting in slower following capacity. During maturation, inhibitory duration gradually shortened accompanied by an improving temporal following ability of RS neurons. Both inhibitory duration and stimulus-following ability demonstrated exposure-based plasticity. These results demonstrate the role of inhibition in setting the pace for experience-dependent maturation of temporal processing in the auditory cortex.

scholarly journals Three dimensional microelectrodes enable high signal and spatial resolution for neural seizure recordings in brain slices and freely behaving animals

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
P. Wijdenes ◽  
K. Haider ◽  
C. Gavrilovici ◽  
B. Gunning ◽  
M. D. Wolff ◽  
...  
Keyword(s):  
Spatial Resolution ◽  
Signal To Noise Ratio ◽  
Brain Activity ◽  
Three Dimensional ◽  
Brain Slices ◽  
High Signal ◽  
Diagnostic Potential ◽  
Freely Behaving

AbstractNeural recordings made to date through various approaches—both in-vitro or in-vivo—lack high spatial resolution and a high signal-to-noise ratio (SNR) required for detailed understanding of brain function, synaptic plasticity, and dysfunction. These shortcomings in turn deter the ability to further design diagnostic, therapeutic strategies and the fabrication of neuro-modulatory devices with various feedback loop systems. We report here on the simulation and fabrication of fully configurable neural micro-electrodes that can be used for both in vitro and in vivo applications, with three-dimensional semi-insulated structures patterned onto custom, fine-pitch, high density arrays. These microelectrodes were interfaced with isolated brain slices as well as implanted in brains of freely behaving rats to demonstrate their ability to maintain a high SNR. Moreover, the electrodes enabled the detection of epileptiform events and high frequency oscillations in an epilepsy model thus offering a diagnostic potential for neurological disorders such as epilepsy. These microelectrodes provide unique opportunities to study brain activity under normal and various pathological conditions, both in-vivo and in in-vitro, thus furthering the ability to develop drug screening and neuromodulation systems that could accurately record and map the activity of large neural networks over an extended time period.

scholarly journals Reactivation of critical period plasticity in adult auditory cortex through chemogenetic silencing of parvalbumin-positive interneurons

2019 ◽  
Vol 116 (52) ◽  
pp. 26329-26331 ◽  
Author(s):  
J. Miguel Cisneros-Franco ◽  
Étienne de Villers-Sidani
Keyword(s):  
Auditory Cortex ◽  
Sensory Processing ◽  
Cortical Plasticity ◽  
Cell Activity ◽  
Sound Intensity ◽  
Cortical Inhibition ◽  
Critical Periods ◽  
Cellular Mechanisms ◽  
Perineuronal Net ◽  
Early Developmental

Sensory experience during early developmental critical periods (CPs) has profound and long-lasting effects on cortical sensory processing perduring well into adulthood. Although recent evidence has shown that reducing cortical inhibition during adulthood reinstates CP plasticity, the precise cellular mechanisms are not well understood. Here, we show that chemogenetic inactivation of parvalbumin-positive (PV+) interneurons is sufficient to reinstate CP plasticity in the adult auditory cortex. Bidirectional manipulation of PV+cell activity affected neuronal spectral and sound intensity selectivity and, in the case of PV+interneuron inactivation, was mirrored by anatomical changes in PV and associated perineuronal net expression. These findings underscore the importance of sustained PV-mediated inhibitory neurotransmission throughout life and highlight the potential of chemogenetic approaches for harnessing cortical plasticity with the ultimate goal of aiding recovery from brain injury or disease.

The Effect of Weak Background Noise on The Frequency Tuning of Neurons in The Rat Auditory Cortex*

2012 ◽  
Vol 39 (11) ◽  
pp. 1082-1088
Author(s):  
Yin-Ting PENG ◽  
Qing PU ◽  
Xin-De SUN ◽  
Ji-Ping ZHANG
Keyword(s):  
Auditory Cortex ◽  
Background Noise ◽  
Frequency Tuning

Dehydroepiandrosterone (DHEA) and its Sulphate (DHEAS) in Alzheimer’s Disease

2020 ◽  
Vol 17 (2) ◽  
pp. 141-157 ◽  
Author(s):  
Dubravka S. Strac ◽  
Marcela Konjevod ◽  
Matea N. Perkovic ◽  
Lucija Tudor ◽  
Gordana N. Erjavec ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Large Scale ◽  
Therapeutic Potential ◽  
Relevant Literature ◽  
Comprehensive Overview ◽  
Brain Functions ◽  
Specific Effects ◽  
And Behavior

Background: Neurosteroids Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone Sulphate (DHEAS) are involved in many important brain functions, including neuronal plasticity and survival, cognition and behavior, demonstrating preventive and therapeutic potential in different neuropsychiatric and neurodegenerative disorders, including Alzheimer’s disease. Objective: The aim of the article was to provide a comprehensive overview of the literature on the involvement of DHEA and DHEAS in Alzheimer’s disease. Method: PubMed and MEDLINE databases were searched for relevant literature. The articles were selected considering their titles and abstracts. In the selected full texts, lists of references were searched manually for additional articles. Results: We performed a systematic review of the studies investigating the role of DHEA and DHEAS in various in vitro and animal models, as well as in patients with Alzheimer’s disease, and provided a comprehensive discussion on their potential preventive and therapeutic applications. Conclusion: Despite mixed results, the findings of various preclinical studies are generally supportive of the involvement of DHEA and DHEAS in the pathophysiology of Alzheimer’s disease, showing some promise for potential benefits of these neurosteroids in the prevention and treatment. However, so far small clinical trials brought little evidence to support their therapy in AD. Therefore, large-scale human studies are needed to elucidate the specific effects of DHEA and DHEAS and their mechanisms of action, prior to their applications in clinical practice.

scholarly journals A New Transgenic Mouse Line for Imaging Mitochondrial Calcium Signals

Function ◽  
2021 ◽  
Vol 2 (3) ◽  
Author(s):  
Nelly Redolfi ◽  
Elisa Greotti ◽  
Giulia Zanetti ◽  
Tino Hochepied ◽  
Cristina Fasolato ◽  
...  
Keyword(s):  
Transgenic Mouse ◽  
Fluorescent Protein ◽  
Ex Vivo ◽  
Brain Slices ◽  
Resonance Energy ◽  
Mouse Line ◽  
Isolated Cells ◽  
Genomic Locus ◽  
Transgenic Mouse Line

AbstractMitochondria play a key role in cellular calcium (Ca2+) homeostasis. Dysfunction in the organelle Ca2+ handling appears to be involved in several pathological conditions, ranging from neurodegenerative diseases, cardiac failure and malignant transformation. In the past years, several targeted green fluorescent protein (GFP)-based genetically encoded Ca2+ indicators (GECIs) have been developed to study Ca2+ dynamics inside mitochondria of living cells. Surprisingly, while there is a number of transgenic mice expressing different types of cytosolic GECIs, few examples are available expressing mitochondria-localized GECIs, and none of them exhibits adequate spatial resolution. Here we report the generation and characterization of a transgenic mouse line (hereafter called mt-Cam) for the controlled expression of a mitochondria-targeted, Förster resonance energy transfer (FRET)-based Cameleon, 4mtD3cpv. To achieve this goal, we engineered the mouse ROSA26 genomic locus by inserting the optimized sequence of 4mtD3cpv, preceded by a loxP-STOP-loxP sequence. The probe can be readily expressed in a tissue-specific manner upon Cre recombinase-mediated excision, obtainable with a single cross. Upon ubiquitous Cre expression, the Cameleon is specifically localized in the mitochondrial matrix of cells in all the organs and tissues analyzed, from embryos to aged animals. Ca2+ imaging experiments performed in vitro and ex vivo in brain slices confirmed the functionality of the probe in isolated cells and live tissues. This new transgenic mouse line allows the study of mitochondrial Ca2+ dynamics in different tissues with no invasive intervention (such as viral infection or electroporation), potentially allowing simple calibration of the fluorescent signals in terms of mitochondrial Ca2+ concentration ([Ca2+]).

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