3,768 research outputs found
Gain control with A-type potassium current: IA as a switch between divisive and subtractive inhibition
Neurons process information by transforming barrages of synaptic inputs into
spiking activity. Synaptic inhibition suppresses the output firing activity of
a neuron, and is commonly classified as having a subtractive or divisive effect
on a neuron's output firing activity. Subtractive inhibition can narrow the
range of inputs that evoke spiking activity by eliminating responses to
non-preferred inputs. Divisive inhibition is a form of gain control: it
modifies firing rates while preserving the range of inputs that evoke firing
activity. Since these two "modes" of inhibition have distinct impacts on neural
coding, it is important to understand the biophysical mechanisms that
distinguish these response profiles.
We use simulations and mathematical analysis of a neuron model to find the
specific conditions for which inhibitory inputs have subtractive or divisive
effects. We identify a novel role for the A-type Potassium current (IA). In our
model, this fast-activating, slowly- inactivating outward current acts as a
switch between subtractive and divisive inhibition. If IA is strong (large
maximal conductance) and fast (activates on a time-scale similar to spike
initiation), then inhibition has a subtractive effect on neural firing. In
contrast, if IA is weak or insufficiently fast-activating, then inhibition has
a divisive effect on neural firing. We explain these findings using dynamical
systems methods to define how a spike threshold condition depends on synaptic
inputs and IA.
Our findings suggest that neurons can "self-regulate" the gain control
effects of inhibition via combinations of synaptic plasticity and/or modulation
of the conductance and kinetics of A-type Potassium channels. This novel role
for IA would add flexibility to neurons and networks, and may relate to recent
observations of divisive inhibitory effects on neurons in the nucleus of the
solitary tract.Comment: 20 pages, 11 figure
Gain Control With A-Type Potassium Current: IA As A Switch Between Divisive And Subtractive Inhibition
Neurons process and convey information by transforming barrages of synaptic inputs into spiking activity. Synaptic inhibition typically suppresses the output firing activity of a neuron, and is commonly classified as having a subtractive or divisive effect on a neuron’s output firing activity. Subtractive inhibition can narrow the range of inputs that evoke spiking activity by eliminating responses to non-preferred inputs. Divisive inhibition is a form of gain control: it modifies firing rates while preserving the range of inputs that evoke firing activity. Since these two “modes” of inhibition have distinct impacts on neural coding, it is important to understand the biophysical mechanisms that distinguish these response profiles. In this study, we use simulations and mathematical analysis of a neuron model to find the specific conditions (parameter sets) for which inhibitory inputs have subtractive or divisive effects. Significantly, we identify a novel role for the A-type Potassium current (IA). In our model, this fast-activating, slowly-inactivating outward current acts as a switch between subtractive and divisive inhibition. In particular, if IA is strong (large maximal conductance) and fast (activates on a time-scale similar to spike initiation), then inhibition has a subtractive effect on neural firing. In contrast, if IA is weak or insufficiently fast-activating, then inhibition has a divisive effect on neural firing. We explain these findings using dynamical systems methods (plane analysis and fast-slow dissection) to define how a spike threshold condition depends on synaptic inputs and IA. Our findings suggest that neurons can “self-regulate” the gain control effects of inhibition via combinations of synaptic plasticity and/or modulation of the conductance and kinetics of A-type Potassium channels. This novel role for IA would add flexibility to neurons and networks, and may relate to recent observations of divisive inhibitory effects on neurons in the nucleus of the solitary tract
Mechanisms of gain control by voltage-gated channels in intrinsically-firing neurons.
This is the final published version. It first appeared at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0115431.Gain modulation is a key feature of neural information processing, but underlying mechanisms remain unclear. In single neurons, gain can be measured as the slope of the current-frequency (input-output) relationship over any given range of inputs. While much work has focused on the control of basal firing rates and spike rate adaptation, gain control has been relatively unstudied. Of the limited studies on gain control, some have examined the roles of synaptic noise and passive somatic currents, but the roles of voltage-gated channels present ubiquitously in neurons have been less explored. Here, we systematically examined the relationship between gain and voltage-gated ion channels in a conductance-based, tonically-active, model neuron. Changes in expression (conductance density) of voltage-gated channels increased (Ca2+ channel), reduced (K+ channels), or produced little effect (h-type channel) on gain. We found that the gain-controlling ability of channels increased exponentially with the steepness of their activation within the dynamic voltage window (voltage range associated with firing). For depolarization-activated channels, this produced a greater channel current per action potential at higher firing rates. This allowed these channels to modulate gain by contributing to firing preferentially at states of higher excitation. A finer analysis of the current-voltage relationship during tonic firing identified narrow voltage windows at which the gain-modulating channels exerted their effects. As a proof of concept, we show that h-type channels can be tuned to modulate gain by changing the steepness of their activation within the dynamic voltage window. These results show how the impact of an ion channel on gain can be predicted from the relationship between channel kinetics and the membrane potential during firing. This is potentially relevant to understanding input-output scaling in a wide class of neurons found throughout the brain and other nervous systems.This work was supported by the Wellcome
Trust- and GSK-funded TMAT programme (085686/
Z/08/C, AXP), the University of Cambridge MB/PhD
Programme (AXP), the European Research Council
(FP7 starting grant to DB) and the UK Medical
Research Council (DB, ref: MC\_UP\_1202/2). The
funders had no role in study design, data collection
and analysis, decision to publish, or preparation of
the manuscript
Energy-efficiency improvements for optical access
This article discusses novel approaches to improve energy efficiency of different optical access technologies, including time division multiplexing passive optical network (TDM-PON), time and wavelength division multiplexing PON (TWDM-PON), point-to-point (PTP) access network, wavelength division multiplexing PON (WDM-PON), and orthogonal frequency division multiple access PON (OFDMA-PON). These approaches include cyclic sleep mode, energy-efficient bit interleaving protocol, power reduction at component level, or frequency band selection. Depending on the target optical access technology, one or a combination of different approaches can be applied
The role of excitation and inhibition in learning and memory formation
The neurons in the mammalian brain can be classified into two broad categories: excitatory and inhibitory neurons. The former has been historically associated to information processing whereas the latter has been linked to network homeostasis. More recently, inhibitory neurons have been related to several computational roles such as the gating of signal propagation, mediation of network competition, or learning. However, the ways by which excitation and inhibition can regulate learning have not been exhaustively explored. Here we explore several model systems to investigate the role of excitation and inhibition in learning and memory formation. Additionally, we investigate the effect that third factors such as neuromodulators and network state exert over this process. Firstly, we explore the effect of neuromodulators onto excitatory neurons and excitatory plasticity. Next, we investigate the plasticity rules governing excitatory connections while the neural network oscillates in a sleep-like cycle, shifting between Up and Down states. We observe that this plasticity rule depends on the state of the network. To study the role of inhibitory neurons in learning, we then investigate the mechanisms underlying place field emergence and consolidation. Our simulations suggest that dendrite-targeting interneurons play an important role in both promoting the emergence of new place fields and in ensuring place field stabilization. Soma-targeting interneurons, on the other hand, are suggested to be related to quick, context-specific changes in the assignment of place and silent cells. We next investigate the mechanisms underlying the plasticity of synaptic connections from specific types of interneurons. Our experiments suggest that different types of interneurons undergo different synaptic plasticity rules. Using a computational model, we implement these plasticity rules in a simplified network. Our simulations indicate that the interaction between the different forms of plasticity account for the development of stable place fields across multiple environments. Moreover, these plasticity rules seems to be gated by the postsynaptic membrane voltage. Inspired by these findings, we propose a voltage-based inhibitory synaptic plasticity rule. As a consequence of this rule, the network activity is kept controlled by the imposition of a maximum pyramidal cell firing rate. Remarkably, this rule does not constrain the postsynaptic firing rate to a narrow range. Overall, through multiple stages of interactions between experiments and computational simulations, we investigate the effect of excitation and inhibition in learning. We propose mechanistic explanations for experimental data, and suggest possible functional implications of experimental findings. Finally, we proposed a voltage-based inhibitory synaptic plasticity model as a mechanism for flexible network homeostasis.Open Acces
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Synthesis of neuromorphic circuits with neuromodulatory properties
The field of neuromorphic engineering shows great promise in delivering novel devices inspired by biological principles that would undertake sensory and processing tasks with an unprecedented level of efficiency. In order to achieve that, engineers are required to understand and implement the many complex biological regulatory mechanisms that allow the nervous system to robustly operate and adapt over scales covering many orders of magnitude, while at the same time using unreliable and noisy components.
As a step towards that, this thesis aims at discussing and implementing the principles of neuromodulation in neuromorphic hardware, mechanisms which allow neurons to change and regulate their behaviour through the continuous control of their internal currents. We discuss how neural dynamics and its modulation can be broken down into four essential feedback loops, and we introduce a simplified model of the neural membrane respecting this fundamental structure. We present a novel methodology for controlling the neuron's behaviour through the shaping of its I-V curves in distinct timescales, thus characterising the behaviour of the neural circuit through its input-output properties. We show how modulation of the feedback loops affects the behaviour, and importantly, captures the transition between spiking and bursting oscillatory regimes, two major signalling modes of neurons. We then show how the architecture can be easily implemented using well-known neuromorphic building blocks based on subthreshold MOSFET circuits. Finally, we discuss how the excitability switch captured by the model can be exploited in simple network settings, thus opening up the possibility for future research into novel architectures where the control of cellular properties is utilised to shape the global behaviour of the network
Sustained Activation of PV+ Interneurons in Core Auditory Cortex Enables Robust Divisive Gain Control for Complex and Naturalistic Stimuli
Sensory cortices must flexibly adapt their operations to internal states and external requirements. Sustained modulation of activity levels in different inhibitory interneuron populations may provide network-level mechanisms for adjustment of sensory cortical processing on behaviorally relevant timescales. However, understanding of the computational roles of inhibitory interneuron modulation has mostly been restricted to effects at short timescales, through the use of phasic optogenetic activation and transient stimuli. Here, we investigated how modulation of inhibitory interneurons affects cortical computation on longer timescales, by using sustained, network-wide optogenetic activation of parvalbumin-positive interneurons (the largest class of cortical inhibitory interneurons) to study modulation of auditory cortical responses to prolonged and naturalistic as well as transient stimuli. We found highly conserved spectral and temporal tuning in auditory cortical neurons, despite a profound reduction in overall network activity. This reduction was predominantly divisive, and consistent across simple, complex, and naturalistic stimuli. A recurrent network model with power-law input–output functions replicated our results. We conclude that modulation of parvalbumin-positive interneurons on timescales typical of sustained neuromodulation may provide a means for robust divisive gain control conserving stimulus representations
Switchable slow cellular conductances determine robustness and tunability of network states.
Neuronal information processing is regulated by fast and localized fluctuations of brain states. Brain states reliably switch between distinct spatiotemporal signatures at a network scale even though they are composed of heterogeneous and variable rhythms at a cellular scale. We investigated the mechanisms of this network control in a conductance-based population model that reliably switches between active and oscillatory mean-fields. Robust control of the mean-field properties relies critically on a switchable negative intrinsic conductance at the cellular level. This conductance endows circuits with a shared cellular positive feedback that can switch population rhythms on and off at a cellular resolution. The switch is largely independent from other intrinsic neuronal properties, network size and synaptic connectivity. It is therefore compatible with the temporal variability and spatial heterogeneity induced by slower regulatory functions such as neuromodulation, synaptic plasticity and homeostasis. Strikingly, the required cellular mechanism is available in all cell types that possess T-type calcium channels but unavailable in computational models that neglect the slow kinetics of their activation
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