Cian O’Donnell PhD

Cian O'Donnell


Publications:
2015
  Spontaneous action potentials and neural coding in unmyelinated axons
O'Donnell, C & van Rossum, MCW 2015, 'Spontaneous action potentials and neural coding in unmyelinated axons' Neural Computation, vol 27, no. 4, pp. 801-18. DOI: 10.1162/NECO_a_00705

The voltage-gated Na and K channels in neurons are responsible for action potential generation. Because ion channels open and close in a stochastic fashion, spontaneous (ectopic) action potentials can result even in the absence of stimulation. While spontaneous action potentials have been studied in detail in single-compartment models, studies on spatially extended processes have been limited. The simulations and analysis presented here show that spontaneous rate in unmyelinated axon depends nonmonotonically on the length of the axon, that the spontaneous activity has sub-Poisson statistics, and that neural coding can be hampered by the spontaneous spikes by reducing the probability of transmitting the first spike in a train.


General Information
Organisations: Edinburgh Neuroscience.
Authors: O'Donnell, Cian & van Rossum, Mark C W.
Number of pages: 18
Pages: 801-18
Publication Date: Apr 2015
Publication Information
Category: Article
Journal: Neural Computation
Volume: 27
Issue number: 4
ISSN: 0899-7667
Original Language: English
DOIs: 10.1162/NECO_a_00705
2014
  Systematic analysis of the contributions of stochastic voltage gated channels to neuronal noise
O'Donnell, C & van Rossum, MCW 2014, 'Systematic analysis of the contributions of stochastic voltage gated channels to neuronal noise' Frontiers in Computational Neuroscience, vol 8, 105. DOI: 10.3389/fncom.2014.00105

Electrical signaling in neurons is mediated by the opening and closing of large numbers of individual ion channels. The ion channels' state transitions are stochastic and introduce fluctuations in the macroscopic current through ion channel populations. This creates an unavoidable source of intrinsic electrical noise for the neuron, leading to fluctuations in the membrane potential and spontaneous spikes. While this effect is well known, the impact of channel noise on single neuron dynamics remains poorly understood. Most results are based on numerical simulations. There is no agreement, even in theoretical studies, on which ion channel type is the dominant noise source, nor how inclusion of additional ion channel types affects voltage noise. Here we describe a framework to calculate voltage noise directly from an arbitrary set of ion channel models, and discuss how this can be use to estimate spontaneous spike rates.


General Information
Organisations: School of Informatics.
Authors: O'Donnell, Cian & van Rossum, Mark C W.
Publication Date: 2014
Publication Information
Category: Article
Journal: Frontiers in Computational Neuroscience
Volume: 8
ISSN: 1662-5188
Original Language: English
DOIs: 10.3389/fncom.2014.00105
2011
  Dendritic Spine Dynamics Regulate the Long-Term Stability of Synaptic Plasticity
O'Donnell, C, Nolan, M & Van Rossum, M 2011, 'Dendritic Spine Dynamics Regulate the Long-Term Stability of Synaptic Plasticity' Journal of Neuroscience, vol 31, no. 45, pp. 16142-16156. DOI: 10.1523/JNEUROSCI.2520-11.2011
Long-term synaptic plasticity requires postsynaptic influx of Ca2+ and is accompanied by changes in dendritic spine size. Unless Ca2+ influx mechanisms and spine volume scale proportionally, changes in spine size will modify spine Ca2+ concentrations during subsequent synaptic activation. We show that the relationship between Ca2+ influx and spine volume is a fundamental determinant of synaptic stability. If Ca2+ influx is undercompensated for increases in spine size, then strong synapses are stabilized and synaptic strength distributions have a single peak. In contrast, overcompensation of Ca2+ influx leads to binary, persistent synaptic strengths with double-peaked distributions. Biophysical simulations predict that CA1 pyramidal neuron spines are undercompensating. This unifies experimental findings that weak synapses are more plastic than strong synapses, that synaptic strengths are unimodally distributed, and that potentiation saturates for a given stimulus strength. We conclude that structural plasticity provides a simple, local, and general mechanism that allows dendritic spines to foster both rapid memory formation and persistent memory storage.
General Information
Organisations: School of Informatics.
Authors: O'Donnell, Cian, Nolan, Matthew & Van Rossum, Mark.
Keywords: (, , . )
Number of pages: 15
Pages: 16142-16156
Publication Date: 9 Nov 2011
Publication Information
Category: Article
Journal: Journal of Neuroscience
Volume: 31
Issue number: 45
ISSN: 0270-6474
Original Language: English
DOIs: 10.1523/JNEUROSCI.2520-11.2011
  Tuning of synaptic responses: an organizing principle for optimization of neural circuits
O'Donnell, C & Nolan, MF 2011, 'Tuning of synaptic responses: an organizing principle for optimization of neural circuits' Trends in Neurosciences, vol 34, no. 2, pp. 51-60. DOI: 10.1016/j.tins.2010.10.003
Neuron types are classically defined by anatomical and physiological properties that determine how synaptic inputs are integrated. Here, we provide an overview of the evidence that, among neurons of a single type, integration of synaptic responses is further tuned according to the particular function that individual neurons carry out. Recent data suggest that tuning of synaptic responses is not restricted to sensory pathways, but extends to cognitive and motor circuits. We propose that tuning of synaptic integration results from general cellular mechanisms for optimization of information processing that are distinct from, but complementary to, homeostasis and memory storage. These cellular tuning mechanisms might be crucial for distributed computations underlying sensory, motor and cognitive functions.
General Information
Organisations: Centre for Integrative Physiology.
Authors: O'Donnell, Cian & Nolan, M. F..
Keywords: (, , . )
Number of pages: 10
Pages: 51-60
Publication Date: 2011
Publication Information
Category: Article
Journal: Trends in Neurosciences
Volume: 34
Issue number: 2
ISSN: 0166-2236
Original Language: English
DOIs: 10.1016/j.tins.2010.10.003
2010
  Dendritic spines can stabilize synaptic weights
O'Donnell, C, Nolan, M & van Rossum, MCW 2010, 'Dendritic spines can stabilize synaptic weights' Computational and Systems Neuroscience 2010, Salt Lake City, UT, United States, 25/02/10 - 2/03/10, .
General Information
Organisations: Institute for Adaptive and Neural Computation .
Authors: O'Donnell, Cian, Nolan, Matthew & van Rossum, Mark C. W..
Publication Date: 2010
Publication Information
Category: Poster
Original Language: English
  Stochastic Ion Channel Gating in Dendritic Neurons: Morphology Dependence and Probabilistic Synaptic Activation of Dendritic Spikes
Cannon, RC, O'Donnell, C & Nolan, MF 2010, 'Stochastic Ion Channel Gating in Dendritic Neurons: Morphology Dependence and Probabilistic Synaptic Activation of Dendritic Spikes' PLoS Computational Biology, vol 6, no. 8, e1000886. DOI: 10.1371/journal.pcbi.1000886
Neuronal activity is mediated through changes in the probability of stochastic transitions between open and closed states of ion channels. While differences in morphology define neuronal cell types and may underlie neurological disorders, very little is known about influences of stochastic ion channel gating in neurons with complex morphology. We introduce and validate new computational tools that enable efficient generation and simulation of models containing stochastic ion channels distributed across dendritic and axonal membranes. Comparison of five morphologically distinct neuronal cell types reveals that when all simulated neurons contain identical densities of stochastic ion channels, the amplitude of stochastic membrane potential fluctuations differs between cell types and depends on sub-cellular location. For typical neurons, the amplitude of membrane potential fluctuations depends on channel kinetics as well as open probability. Using a detailed model of a hippocampal CA1 pyramidal neuron, we show that when intrinsic ion channels gate stochastically, the probability of initiation of dendritic or somatic spikes by dendritic synaptic input varies continuously between zero and one, whereas when ion channels gate deterministically, the probability is either zero or one. At physiological firing rates, stochastic gating of dendritic ion channels almost completely accounts for probabilistic somatic and dendritic spikes generated by the fully stochastic model. These results suggest that the consequences of stochastic ion channel gating differ globally between neuronal cell-types and locally between neuronal compartments. Whereas dendritic neurons are often assumed to behave deterministically, our simulations suggest that a direct consequence of stochastic gating of intrinsic ion channels is that spike output may instead be a probabilistic function of patterns of synaptic input to dendrites.
General Information
Organisations: Centre for Integrative Physiology.
Authors: Cannon, R. C., O'Donnell, Cian & Nolan, M. F..
Keywords: (, , . )
Number of pages: 18
Publication Date: Aug 2010
Publication Information
Category: Article
Journal: PLoS Computational Biology
Volume: 6
Issue number: 8
ISSN: 1553-734X
Original Language: English
DOIs: 10.1371/journal.pcbi.1000886
2009
  Dendritic spines as devices for synaptic metaplasticity
O'Donnell, C, Nolan, M & van Rossum, MCW 2009, 'Dendritic spines as devices for synaptic metaplasticity' Dendrites: Molecules, Structure & Function, Lucca (Barga), Italy, 17/05/09 - 22/05/09, .
General Information
Organisations: Institute for Adaptive and Neural Computation .
Authors: O'Donnell, Cian, Nolan, Matthew & van Rossum, Mark C. W..
Publication Date: 2009
Publication Information
Category: Poster
Original Language: English
  Stochastic action potentials in axons: a possible role in neuropathic pain
O'Donnell, C, Nolan, M & van Rossum, MCW 2009, 'Stochastic action potentials in axons: a possible role in neuropathic pain' Society for Neuroscience Annual Meeting 2009, Chicago, United States, 17/10/09 - 21/10/09, .
General Information
Organisations: Institute for Adaptive and Neural Computation .
Authors: O'Donnell, Cian, Nolan, Matthew & van Rossum, Mark C. W..
Publication Date: 2009
Publication Information
Category: Poster
Original Language: English
2008
  The impact of stochastic ion channel activity depends on neuronal morphology
O'Donnell, C, van Rossum, MCW, Cannon, RC & Nolan, M 2008, 'The impact of stochastic ion channel activity depends on neuronal morphology' 1st INCF Congress of Neuroinformatics, Stockholm, Sweden, 7/09/08 - 9/09/08, . DOI: 10.3389/conf.neuro.11.2008.01.031
It is well known that the way a neuron integrates its synaptic inputs depends both on its morphology and its dendritic distribution of ion channels. A great deal is also known about the stochastic gating of individual ion channels. However, up to now it has been difficult to incorporate all of these aspects into unified models of single cells. Most studies either use deterministic conductances to abstract the ensemble ion channel activity, or examine stochastic ion channel behaviour in simplified cell morphologies. To investigate the impact of stochastic ion channel gating on membrane noise in realistic cell morphologies, we have used a new simulation system, PSICS, which has been designed to enable efficient simulation of models that incorporate all of these details (http://www.psics.org).

To first investigate the relative contributions of different ion channel populations to membrane noise, we simulated a simple isopotential patch of membrane with stochastic ion channels governed by Hodgkin-Huxley kinetics (after Chow & White, 1996). We find that channels which have larger open probabilities, such as K channels at resting potential in the Hodgkin-Huxley model, contribute more to membrane potential fluctuations, and even to spontaneous action potentials, than channels that have small open probabilities.

We then assessed the role of morphology in determining intrinsic electrical noise by applying an identical suite of ion channels (Mainen & Sejnowski, 1996) to several reconstructed morphologies of different cell types downloaded from an online database (http://www.neuromorpho.org). By systematically varying the resting potential in each cell and recording the voltage fluctuations in multiple dendritic locations, we determine qualitative relationships between intrinsic membrane noise and dendritic morphology. These fluctuations can be substantial (standard deviation ~ 1mV) and depend on factors such as dendritic branching pattern, diameter, location and the level of depolarisation. This work also demonstrates the feasibility of running full stochastic models of electrical activity in single neurons using a new simulator, PSICS.
General Information
Organisations: Centre for Integrative Physiology.
Authors: O'Donnell, Cian, van Rossum, Mark C. W., Cannon, Robert C. & Nolan, Matthew.
Publication Date: 2008
Publication Information
Category: Poster
Original Language: English
DOIs: 10.3389/conf.neuro.11.2008.01.031
  PSICS: a new tool for simulation of stochastic ion channels in neurons with complex dendritic and axonal morphologies
Nolan, M, O'Donnell, C & Cannon, RC 2008, 'PSICS: a new tool for simulation of stochastic ion channels in neurons with complex dendritic and axonal morphologies' 6th FENS Forum of European Neuroscience, Geneva, Switzerland, 12/07/08 - 16/07/08, .
How a neuron processes its inputs is profoundly influenced by the distribution of ion channels on its axons and dendrites. Although a great deal is know about the gating of single ion channels, relatively few models of signal processing in neurons account for stochastic fluctuations in single ion channel activity. It has been particularly difficult to investigate the consequences of stochastic ion channel gating in the fine dendritic and axonal processes of neurons with complex morphologies, yet these areas of the cell are where stochastic fluctuations may have greatest functional impact. Here we introduce Parallel Stochastic Ion Channel Simulator (PSICS), a new computational tool that enables efficient and straightforward generation, simulation and visualization of models containing stochastic ion channels distributed across dendritic or axonal structures. PSICS allows arbitrary distribution of individual ion channels while also substantially reducing the time required for accurate stochastic simulations of electrical activity in neurons with complex morphologies. We demonstrate the use of PSICS by evaluating the consequences of stochastic ion channel gating in neurons with distinct dendritic architectures.
General Information
Organisations: Neuroinformatics DTC.
Authors: Nolan, Matthew, O'Donnell, Cian & Cannon, Robert C..
Publication Date: 2008
Publication Information
Category: Poster
Original Language: English
  Tuning of Synaptic Integration in the Medial Entorhinal Cortex to the Organization of Grid Cell Firing Fields
Garden, DLF, Dodson, PD, O'Donnell, C, White, MD & Nolan, MF 2008, 'Tuning of Synaptic Integration in the Medial Entorhinal Cortex to the Organization of Grid Cell Firing Fields' Neuron, vol 60, no. 5, pp. 875-889. DOI: 10.1016/j.neuron.2008.10.044
Neurons important for cognitive function are often classified by their morphology and integrative properties. However, it is unclear if within a single class of neuron these properties tune synaptic responses to the salient features of the information that each neuron represents. We demonstrate that for stellate neurons in layer 11 of the medial entorhinal cortex, the waveform of postsynaptic potentials, the time window for detection of coincident inputs, and responsiveness to gamma frequency inputs follow a dorsal-ventral gradient similar to the topographical organization of grid-like spatial firing fields of neurons in this area. We provide evidence that these differences are due to a membrane conductance gradient mediated by HCN and leak potassium channels. These findings suggest key roles for synaptic integration in computations carried out within the medial entorhinal cortex and imply that tuning of neural information processing by membrane ion channels is important for normal cognitive function.
General Information
Organisations: Neuroinformatics DTC.
Authors: Garden, D. L. F., Dodson, P. D., O'Donnell, Cian, White, M. D. & Nolan, M. F..
Keywords: (Animals, Bone and Bones/ chemistry, Cattle, Creutzfeldt-Jakob Syndrome/prevention & control/transmission, Encephalopathy, Bovine Spongiform/prevention & control/transmission, Gelatin/ chemistry, Hot Temperature, Humans, Hydrolysis, Mice, Pressure, Prions/ pathogenicity, Time Factors, , , . )
Number of pages: 15
Pages: 875-889
Publication Date: Dec 2008
Publication Information
Category: Article
Journal: Neuron
Volume: 60
Issue number: 5
ISSN: 0896-6273
Original Language: English
DOIs: 10.1016/j.neuron.2008.10.044
2007
  Dendritic computation in entorhinal cortex stellate cells
O'Donnell, C 2007, 'Dendritic computation in entorhinal cortex stellate cells'.
General Information
Organisations: Neuroinformatics DTC.
Authors: O'Donnell, Cian.
Publication Date: 2007
Publication Information
Category: Poster
Original Language: English

Projects:
Dendritic spine plasticity and synaptic plasticity (MRes)
Stochastic ion channels in thin axons and neuropathic pain (PhD)