Measurement of phase resetting curves using optogenetic barrage stimuli.

Friday, September 1, 2017

Matthew H. Higgs, Charles J. Wilson J Neurosci Methods. 289:23-30.

Background: The phase resetting curve (PRC) is a primary measure of a rhythmically firing neuron's responses to synaptic input, quantifying the change in phase of the firing oscillation as a function of the input phase. PRCs provide information about whether neurons will synchronize due to synaptic coupling or shared input. However, PRC estimation has been limited to in vitro preparations where stable intracellular recordings can be obtained and background activity is minimal, and new methods are required for in vivo applications.New method: We estimated PRCs using dense optogenetic stimuli and extracellular...

Predicting the response of striatal spiny neurons to sinusoidal input.

Tuesday, August 1, 2017

Charles J. Wilson J Neurophysiol. 118(2):855-873.

Spike timing effects of small amplitude sinusoidal currents were measured in mouse striatal spiny neurons firing repetitively.  Spike timing reliability varied with the stimulus frequency.  For frequencies near the cell’s firing rate, the cells altered firing rate to match the stimulus and became phase-locked to it. The stimulus phase of firing during lock depended on the stimulus frequency relative to the cell’s unperturbed firing rate. Interspike intervals during sinusoidal stimulation were predicted using an iterative map constructed from the cells’ phase resetting curve.  Variability of interspike intervals was...

Effect of Phase Response Curve Shape and Synaptic Driving Force on Synchronization of Coupled Neuronal Oscillators.

Monday, June 19, 2017

Ramana Dodla, Charles J. Wilson Neural Comput. 29(7):1769-1814.

The role of the phase response curve (PRC) shape on the synchrony of synaptically coupled oscillating neurons is examined. If the PRC is independent of the phase, because of the synaptic form of the coupling, synchrony is found to be stable for both excitatory and inhibitory coupling at all rates whereas the antisynchrony becomes stable at low rates. A faster synaptic rise helps extend the stability of antisynchrony to higher rates. If the PRC is not constant, but has a profile like that of a leaky integrates-and-fire model, then, in contrast to the earlier reports that did not include the voltage effects,...

The ionic mechanism of membrane potential oscillations and membrane resonance in striatal LTS interneurons.

Saturday, October 1, 2016

Soomin C. Song, Joseph A. Beatty, Charles J. Wilson. J Neurophysiol. 116(4):1752-1764.

Striatal low-threshold spiking (LTS) interneurons spontaneously transition to a depolarized, oscillating state similar to that seen after sodium channels are blocked.  In the depolarized state, whether spontaneous or induced by sodium channel blockade, the neurons express a 3 – 7 Hz oscillation and membrane impedance resonance in the same frequency range.  The membrane potential oscillation and membrane resonance are expressed in the same voltage range (> -40 mV).  We identified and recorded from LTS interneurons in striatal slices from a mouse that expressed GFP under the control...

Unitary synaptic connections among substantia nigra pars reticulata neurons.

Wednesday, June 1, 2016

Matthew H. Higgs and Charles J. Wilson. J Neurophysiol. 115(6):2814-29.

Neurons in substantia nigra pars reticulata (SNr) are synaptically coupled by local axon collaterals, providing a potential mechanism for local signal processing. Because SNr neurons fire spontaneously, these synapses are constantly active. To investigate their properties, we recorded spontaneous IPSCs (sIPSCs) from SNr neurons in brain slices, in which afferents from upstream nuclei are severed and the cells fire rhythmically. The sIPSC trains contained a mixture of periodic and aperiodic events. Autocorrelation analysis of sIPSC trains showed that a majority of cells had 1-4 active unitary inputs....

An inhibitory corticostriatal pathway

Monday, May 9, 2016

Crystal Rock, Hector Zurita, Charles J Wilson, Alfonso junior Apicella Elife. 2016 May 9;5. pii: e15890.

Anatomical and physiological studies have led to the assumption that the dorsal striatum receives exclusively excitatory afferents from the cortex. Here we test the hypothesis that the dorsal striatum receives also GABAergic projections from the cortex. We addressed this fundamental question by taking advantage of optogenetics and directly examining the functional effects of cortical GABAergic inputs to spiny projection neurons (SPNs) of the mouse auditory and motor cortex. We found that the cortex, via corticostriatal somatostatin neurons (CS-SOM), has a direct...

Oscillators and Oscillations in the Basal Ganglia.

Sunday, October 18, 2015

Charles J. Wilson Neuroscientist.21(5):530-539.

What is the meaning of an action potential?  There must be different answers for neurons that fire spontaneously, even in the absence of synaptic input, and those driven to fire from a resting membrane potential. In spontaneously firing neurons, the occurrence of the next action potential is guaranteed; only variations in its timing can carry the message. In the basal ganglia the globus pallidus, the substantia nigra, and the subthalamic nucleus consist of neurons firing spontaneously. They each receive thousands of synaptic inputs, but these are not required to maintain their background firing. Instead, synaptic interactions...

Cell-type-specific resonances shape the responses of striatal neurons to synaptic input.

Wednesday, February 18, 2015

Joseph A. Beatty, Soomin C. Song and Charles J. Wilson J Neurophysiol. 13(3):688-700.

Neurons respond to synaptic inputs in cell-type specific ways. Each neuron type may thus respond uniquely to shared patterns of synaptic input. We applied statistically identical barrages of artificial synaptic inputs to four striatal cell types to assess differences in their responses to a realistic input pattern. Each interneuron type fired in phase with a specific input frequency component. The fast-spiking interneuron fired in relation to the gamma-band (and higher) frequencies, the low-threshold spike interneuron to beta-band, and the cholinergic neurons to delta-band frequencies....

Predicting the responses of repetitively firing neurons to current noise

Thursday, May 8, 2014

Charles J. Wilson, David Barraza, Todd Troyer, and Michael A. Farries  PLoS Comput. BIol. 10:e1003612 

We used phase resetting methods to predict firing patterns of rat subthalamic nucleus (STN) neurons when their rhythmic firing was densely perturbed by noise. We applied sequences of contiguous brief (0.5-2 ms) current pulses with amplitudes drawn from a Gaussian distribution (10-100 pA standard deviation) to autonomously firing STN neurons in slices. Current noise sequences increased the variability of spike times with little or no effect on the average firing rate. We measured the infinitesimal phase resetting curve (PRC) for each neuron using a noise-based method....

Firing rate and pattern heterogeneity in the globus pallidus arise from a single neuron population

Friday, November 15, 2013

Deister CA, Dodla R, Barraza D, Kita H, and Wilson C.J.  J Neurophysiol.109:497-506.

Intrinsic heterogeneity in networks of interconnected cells types has profound effects on synchrony and spike-time reliability of network responses.  Projection neurons of the globus pallidus (GPe) are interconnected by GABAergic inhibitory synapses and in vivo fire continuously, but display significant rate and firing pattern heterogeneity.  Despite being deprived of most of their synaptic inputs, GPe neurons in slices also fire continuously, and vary greatly in their firing rate (1-70 spikes/s) and in regularity of their firing.  We asked if this rate and pattern heterogeneity arises...

Effect of phase response curve skewness on synchronization of electrically coupled neuronal oscillators.

Friday, October 25, 2013

Ramana Dodla and Charles J. Wilson  Neural Computation 10:2545-2610.

We investigate why electrically coupled neuronal oscillators synchronize or fail to synchronize using the theory of weakly coupled oscillators. Stability of synchrony and antisynchrony is predicted analytically and verified using numerical bifurcation diagrams. The shape of the phase response curve (PRC), the shape of the voltage time course, and the fre- quency of spiking are freely varied to map out regions of parameter spaces that hold stable solutions. We find that type 1 and type 2 PRCs can hold both synchronous and antisynchronous solutions, but the shape of the PRC and the voltage determine...

Interaction function of oscillating coupled neurons.

Tuesday, October 15, 2013

Ramana Dodla and Charles J. Wilson  Phys Rev E Stat Nonlin Soft Matter Phys. 88:042704

Large scale simulations of electrically coupled neuronal oscillators often employ the phase coupled oscillator paradigm to understand and predict network behavior. We study the nature of the interaction between such coupled oscillators using weakly coupled oscillator theory. By employing piecewise linear approximations for phase response curves and voltage time courses, and parameterizing their shapes, we compute the interaction function for all such possible shapes and express it in terms of discrete Fourier modes. We find that reasonably good approximation is achieved with four...

Active decorrelation in the basal ganglia.

Thursday, October 10, 2013

Charles J. Wilson  Neuroscience 250:467-482.

The cytoarchitecturally-homogeneous appearance of the globus pallidus, subthalamic nucleus and substantia nigra has long been said to imply a high degree of afferent convergence and sharing of inputs by nearby neurons.  Moreover, axon collaterals of neurons in the external segment of the globus pallidus and the substantia nigra pars reticulata arborize locally and make inhibitory synapses on other cells of the same type.  These features suggest that the connectivity of the basal ganglia may impose spike-time correlations among the cells, and it has been puzzling that experimental studies have failed to demonstrate such correlations....

Spike width and frequency alter stability of phase-locking in electrically coupled neurons

Saturday, April 13, 2013

Ramana Dodla and Charles J. Wilson  Biol. Cybern.107:367-383.

The stability of phase-locked states of electrically coupled type-1 phase response curve neurons is studied using piecewise linear formulations for their voltage profile and phase response curves. We find that at low frequency and/or small spike width, synchrony is stable, and antisynchrony unstable. At high frequency and/or large spike width, these phase-locked states switch their stability. Increasing the ratio of spike width to spike height causes the antisynchronous state to transition into a stable synchronous state. We compute the interaction function and the boundaries of stability of both these phase-locked...

Effect of sharp jumps at the edges of phase response curves on synchronization of electrically coupled neuronal oscillators.

Wednesday, March 13, 2013

Ramana Dodla and Charles J. Wilson  PLoS One 8:e58922.

We study synchronization phenomenon of coupled neuronal oscillators using the theory of weakly coupled oscillators. The role of sudden jumps in the phase response curve profiles found in some experimental recordings and models on the ability of coupled neurons to exhibit synchronous and antisynchronous behavior is investigated, when the coupling between the neurons is electrical. The level of jumps in the phase response curve at either end, spike width and frequency of voltage time course of the coupled neurons are parameterized using piecewise linear functional forms, and the conditions for stable synchrony and...

Phase response curves of subthalamic neurons measured with synaptic input and current injection.

Monday, October 15, 2012

Michael A. Farries and Charles J. Wilson  J. Neurophysiol. 108:1822-1837.

Infinitesimal phase response curves (iPRCs) provide a simple description of the response of repetitively firing neurons, and may be used to predict responses to any pattern of synaptic input.  Their simplicity makes them useful for understanding the dynamics of neurons, when certain conditions are met.  For example, the sizes of evoked phase shifts should scale linearly with stimulus strength, and the form of the iPRC should remain relatively constant as firing rate varies. We measured the PRCs of rat subthalamic neurons in brain slices using corticosubthalamic EPSPs (mediated by both AMPA- and...

Biophysical basis of the phase response curve of subthalamic neurons.

Saturday, October 13, 2012

Michael A. Farries and Charles J. Wilson J. Neurophysiol. 108:1838-1855.

Experimental evidence indicates that the response of subthalamic neurons to EPSPs is well described by their infinitesimal phase response curves (iPRC).  However, the factors controlling the shape of that iPRC--and hence controlling the way subthalamic neurons respond to synaptic input--are unclear.  We developed a biophysical model of subthalamic neurons to aid in the understanding of their iPRCs; this model exhibited an iPRC type common to many subthalamic cells.  We devised a method for deriving its iPRC from its biophysical properties that clarifies how these different properties interact...

Complex autonomous firing patterns of striatal low-threshold spike interneurons.

Monday, August 13, 2012

Beatty J.A., Sullivan, M.A., Morikawa, H. and Wilson C.J. J. Neurophysiol. 108:771-781

During sensorimotor learning, tonically active neurons (TANs) in the striatum acquire bursts and pauses in their firing based on the salience of the stimulus.  Striatal cholinergic interneurons display tonic intrinsic firing, even in the absence of synaptic input, that resembles TAN activity seen in vivo.  But whether there are other striatal neurons among the group identified as TANs is unknown.  We used transgenic mice expressing green fluorescent protein under control of neuronal nitric oxide synthase or neuropeptide-Y promoters to aid in identifying low-threshold spike (LTS)...

The ionic mechanism of gamma resonance in striatal fast-spiking neurons

Tuesday, December 13, 2011

Giuseppe Sciamanna and Charles J. Wilson J. Neurophysiol. 106:2936-2949.

Striatal fast spiking (FS) cells in slices fire in the gamma frequency range, and in vivo are often phase-locked to gamma oscillations in the field potential.  We studied the firing patterns of these cells in slices from rats aged 16-23 days, to determine the mechanism of their gamma-resonance.  The resonance of striatal FS cells was manifested as a minimum frequency for repetitive firing.  At rheobase, cells fired a doublet of action potentials or doublets separated by pauses, with an instantaneous firing rate averaging 44 spikes/s.   The minimum rate for sustained firing was also responsible...

Intrinsic dynamics and synaptic inputs control the activity patterns of subthalamic nucleus neuron in health and in Parkinson's disease.

Tuesday, December 13, 2011

Charles J. Wilson, Mark D. Bevan Neuroscience 198:54-68.

Neurons in the subthalamic nucleus occupy a pivotal position in the circuitry of the basal ganglia.  They receive direct excitatory input from the cerebral cortex and the intralaminar nuclei of the thalamus, and directly excite the inhibitory basal ganglia output neurons in the internal segment of the globus pallidus and the substantia nigra. They are also engaged in a reciprocal synaptic arrangement with inhibitory neurons in the external segment of the globus pallidus.  Although once viewed as a simple relay of extrinsic input to the basal ganglia, physiological studies of subthalamic neurons have revealed...

Chaotic desynchronization as the therapeutic mechanism of deep brain stimulation

Wednesday, July 13, 2011

Charles J. Wilson, Bryce Beverlin II, Theoden Netoff Frontiers System Neurosci. 2011, 5:50.

High frequency deep-brain stimulation of the subthalamic nucleus (DBS) relieves many of the symptoms of Parkinson's disease in humans and animal models.   Although the treatment has seen widespread use, its therapeutic mechanism remains paradoxical.  The subthalamic nucleus is excitatory, so its stimulation at rates higher than its normal firing rate should worsen the disease by increasing subthalamic excitation of the globus pallidus.  The therapeutic effectiveness of DBS is also frequency and intensity sensitive, and the stimulation must be periodic; aperiodic stimulation...