Strength Of Inhibitory Inputs Research Articles

A Cerebellar Spiking Neural Model for Phase Reversal of Vestibulo-ocular Reflex.

Cerebellum possesses very rich motor control and learning capability which is critical for animals. In this study, we proposed a spiking neural network model of cerebellum for gain and phase adaptation in vestibulo-ocular reflex (VOR). VOR is a critical adaptive reflexive eye movement for maintaining a stable visual field. In this model (with neuron number at the order of 104), synaptic plasticity at parallel fiber-Purkinje cell synapses was considered. In particular, we have shown that the inhibitory inputs from molecular layer interneurons on Purkinje cells play a critical role in phase adaptation of VOR. The inhibitory input from interneurons indirectly affects the strength of long-term potentiation (LTP) and long-term depression (LTD), resulting in more drastic phase shift upon learning and hence allowing phase reversal of VOR. The strength of inhibitory input also affects the maximum phase shift that can be achieved. Our result is consistent with experiments in mutant mice with blocked inhibitory inputs.

Brief mindfulness training alters causal brain connections in mTBI

Traumatic brain injury (TBI) is a significant cause of disability in the United States and the mild TBI (mTBI) is the most prevalent. Previous research indicates the positive effect of mindfulness training on symptoms of chronic mTBI such as cognitive functioning and emotion [1]. However it remains unclear which brain regions play a crucial role in mTBI recovery and the causal relationship among these regions. Here we apply a dynamic causal modeling (DCM) in resting state fMRI [2] to demonstrate the causal relationships among the core regions involved in mTBI. Fourteen veteran students with mTBI were recruited through campus advertisements. We used 2 weeks of integrative body-mind training as mindfulness intervention, previously reported in our series of randomized studies [3,4]. All data were collected using a 3-Telsa Siemens Skyra scanner. Functional data were processed using the Data Processing Assistant for Resting-State fMRI, which is based on SPM and Resting-State fMRI Data Analysis Toolkit. Based on literature, we specified four regions of interest within default mode network (DMN) - medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), and bilateral inferior parietal lobule (Left IPL and Right IPL), same regions and coordinates as in previous sDCM studies [2,5]. Based on SPM12, we estimated and specified the DCM for each subject and later compared the differences of effective connectivity before and after mindfulness. Our results suggest the different causal relationships following mindfulness training. Specifically, after training there was a significant decrease in the strength of excitatory input from mPFC to PCC, and a significant increase in the strength of inhibitory input from mPFC to LIPL (all p<0.05).

Maternal Loss of Ube3a Produces an Excitatory/Inhibitory Imbalance through Neuron Type-Specific Synaptic Defects

Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of the maternally inherited allele of UBE3A. AS model mice, which carry a maternal Ube3a null mutation (Ube3a(m-/p+)), recapitulate major features of AS in humans, including enhanced seizure susceptibility. Excitatory neurotransmission onto neocortical pyramidal neurons is diminished in Ube3a(m-/p+) mice, seemingly at odds with enhanced seizure susceptibility. We show here that inhibitory drive onto neocortical pyramidal neurons is more severely decreased in Ube3a(m-/p+) mice. This inhibitory deficit follows the loss of excitatory inputs and appears to arise from defective presynaptic vesicle cycling in multiple interneuron populations. In contrast, excitatory and inhibitory synaptic inputs onto inhibitory interneurons are largely normal. Our results indicate that there are neuron type-specific synaptic deficits in Ube3a(m-/p+) mice despite the presence of Ube3a in all neurons. These deficits result in excitatory/inhibitory imbalance at cellular and circuit levels and may contribute to seizure susceptibility in AS.

Mechanisms of generation and suppression of oscillations in the basal ganglia

Event Abstract Back to Event Mechanisms of generation and suppression of oscillations in the basal ganglia Arvind Kumar1, 2, 3*, Ad Aertsen1, 2, Stefan Rotter1, 3 and Stefano Cardanobile1, 3 1 Bernstein Center Freiburg, Germany 2 University of Freiburg, Faculty of Biology, Germany 3 University of Freiburg, Faculty of Biology, Germany Movement disorders in Parkinson's disease (PD) are commonly associated with slow oscillations and increased synchrony of neuronal activity in the basal ganglia. The neural mechanisms underlying this dynamic network dysfunction, however, are only poorly understood. Here, we show that the strength of inhibitory inputs from striatum to globus pallidus external (GPe) is a key parameter controlling oscillations in the basal ganglia. Specifically, the increase in striatal activity observed in PD is sufficient to unleash the oscillations in the basal ganglia. This finding allows us to propose a unified explanation for different phenomena: absence of oscillation in the healthy state of the basal ganglia, oscillations in dopamine-depleted state and quenching of oscillations under deep brain stimulation (DBS). These novel insights help us to better understand and optimize the function of DBS protocols. Furthermore, studying the model behavior under transient increase of activity of the striatal neurons projecting to the indirect pathway, we are able to account for both motor impairment in PD patients and for reduced response inhibition in DBS implanted patients. Acknowledgements Funded in parts by the German Federal Ministry of Education and Research (BMBF grant 01GQ0420 to the BCCN Freiburg, BMBF GW0542 Cognition, and BMBF 01GW0730 Impulse Control). Keywords: Basal Ganglia and Deep Brain Stimulation Conference: BC11 : Computational Neuroscience & Neurotechnology Bernstein Conference & Neurex Annual Meeting 2011, Freiburg, Germany, 4 Oct - 6 Oct, 2011. Presentation Type: Keynote Topic: other Citation: Kumar A, Aertsen A, Rotter S and Cardanobile S (2011). Mechanisms of generation and suppression of oscillations in the basal ganglia. Front. Comput. Neurosci. Conference Abstract: BC11 : Computational Neuroscience & Neurotechnology Bernstein Conference & Neurex Annual Meeting 2011. doi: 10.3389/conf.fncom.2011.53.00028 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 26 Sep 2011; Published Online: 04 Oct 2011. * Correspondence: Dr. Arvind Kumar, Bernstein Center Freiburg, Freiburg, Germany, kumar@bcf.uni-freiburg.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Arvind Kumar Ad Aertsen Stefan Rotter Stefano Cardanobile Google Arvind Kumar Ad Aertsen Stefan Rotter Stefano Cardanobile Google Scholar Arvind Kumar Ad Aertsen Stefan Rotter Stefano Cardanobile PubMed Arvind Kumar Ad Aertsen Stefan Rotter Stefano Cardanobile Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

The Role of Inhibition in Generating and Controlling Parkinson?s Disease Oscillations in the Basal Ganglia

Movement disorders in Parkinson’s disease (PD) are commonly associated with slow oscillations and increased synchrony of neuronal activity in the basal ganglia. The neural mechanisms underlying this dynamic network dysfunction, however, are only poorly understood. Here, we show that the strength of inhibitory inputs from striatum to globus pallidus external (GPe) is a key parameter controlling oscillations in the basal ganglia. Specifically, the increase in striatal activity observed in PD is sufficient to unleash the oscillations in the basal ganglia. This finding allows us to propose a unified explanation for different phenomena: absence of oscillation in the healthy state of the basal ganglia, oscillations in dopamine-depleted state and quenching of oscillations under deep-brain-stimulation (DBS). These novel insights help us to better understand and optimize the function of DBS protocols. Furthermore, studying the model behavior under transient increase of activity of the striatal neurons projecting to the indirect pathway, we are able to account for both motor impairment in PD patients and for reduced response inhibition in DBS implanted patients.

The strength of inhibitory input during education quantitatively tunes the functional responsiveness of individual natural killer cells

Natural killer (NK) cells express inhibitory receptors for major histocompatibility complex (MHC) class I. If self-MHC is down-regulated or absent, lack of inhibition triggers "missing self" killing. NK cells developing in the absence of MHC class I are hypo-responsive, demonstrating that MHC class I molecules are required for NK-cell education. Here, we show that the number and the type of MHC class I alleles that are present during NK-cell education quantitatively determine the frequency of responding NK cells, the number of effector functions in individual NK cells, and the amount of interferon-gamma production in NK cells of specific Ly49 subsets. A relationship between the extent of inhibitory signals during education and functional responsiveness was corroborated by an enhanced probability of NK cells expressing more than one inhibitory receptor for a single host self-MHC class I allele to degranulate after activation. Our data suggest that the capacity of an individual NK cell to respond to stimulation is quantitatively controlled by the extent of inhibitory signals that are received from MHC class I molecules during NK-cell education.