Broadband entrainment of striatal low-threshold spike interneurons
Morales JC, Higgs MH, Song SC and Wilson CJ (2020) Broadband Entrainment of Striatal Low-Threshold Spike Interneurons. Front. Neural Circuits 14:36. doi: 10.3389/fncir.2020.00036
Striatal interneurons and projection neurons are differentially tuned to spectral components of synaptic input signals, and this is especially apparent in their responses to oscillations. The broad frequency tuning of spike responses in somatostatin/NPY-expressing low threshold spike (LTS) interneurons sets them apart from other GABAergic interneurons in the striatum as well as from the spiny projection (SP) neurons. The mechanism of LTS interneuron spiking resonance was unrelated to its...
Indirect pathway control of firing rate and pattern in the substantia nigra pars reticulata
Simmons DV, Higgs MH, Lebby S, Wilson CJ. (2020) Indirect pathway control of firing rate and pattern in the substantia nigra pars reticulata. J Neurophysiol. 2020 Feb 1;123(2):800-814.
Unitary pallidonigral synaptic currents were measured using optogenetic stimulation, which activated up to three unitary synaptic inputs to each SNr cell. Episodic barrages of synaptic conductances were generated based on in vivo firing patterns of GPe cells and applied to SNr cells using conductance clamp. Barrage inputs were compared to continuous step conductances with the same mean. Barrage inputs and steps both slowed SNr neuron firing and produced disinhibition responses seen...
Frequency-dependent entrainment of striatal fast-spiking interneurons
Matthew H. Higgs & Charles J. Wilson (2019) Frequency-dependent entrainment of striatal fast-spiking interneurons. J Neurophysiol 122: 1060–1072, 2019.
Striatal fast-spiking interneurons (FSIs) fire in variable-length runs of action potentials at 20-200/s separated by pauses. In vivo, or with artificial fluctuating applied current, both runs and pauses become briefer and more variable. During runs, spikes are entrained specifically to gamma-frequency components of the input fluctuations. We stimulated striatal FSIs in slices with broadband noise currents added to direct current steps, and measured spike entrainment across all frequencies. As the constant current...
Oscillations and entrainment
Wilson CJ, Higgs, MH, Simmons DV, Morales JC F1000Research (2018) 16451.1 https://doi.org/10.12688/f1000research.16451.1
Abstract:
Oscillatory input to networks, as indicated by field potentials, must entrain neuronal firing to be a causal agent in brain activity. Even when the oscillatory input is prominent, entrainment of firing is not a foregone conclusion, but depends on the intrinsic dynamics of the postsynaptic neurons, including cell type specific resonances, and background firing rates. Within any local network of neurons, only a subset of neurons may have their firing entrained by an oscillating synaptic input, and oscillations of different frequency...
Predicting responses to inhibitory synaptic input in substantia nigra pars reticulata neurons
Simmons DV, Higgs MH, Wilson CJ. J Neurophysiol. 120:2679-2693.
The changes in firing probability produced by a synaptic input are usually visualized using the post-stimulus time histogram (PSTH). It would be useful if postsynaptic firing patterns could be predicted from patterns of afferent synaptic activation, but attempts to predict the PSTH from synaptic potential waveforms using reasoning based on voltage trajectory and spike threshold have not been successful, especially for inhibitory inputs. We measured PSTHs for substantia nigra pars reticulata (SNr) neurons inhibited by optogenetic stimulation of striato-nigral inputs, or by matching artificial inhibitory...
Measurement of phase resetting curves using optogenetic barrage stimuli.
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.
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.
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.
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.
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
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.
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.
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
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
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.
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.
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.
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
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.
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.
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.
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.
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
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.
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
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...