Analysis of the role of the low threshold currents IT and Ih in intrinsic delta oscillations of thalamocortical neurons

Thalamocortical neurons are involved in the generation and maintenance of brain rhythms associated with global functional states. The repetitive burst firing of TC neurons at delta frequencies (1–4 Hz) has been linked to the oscillations recorded during deep sleep and during episodes of absence seizures. To get insight into the biophysical properties that are the basis for intrinsic delta oscillations in these neurons, we performed a bifurcation analysis of a minimal conductance-based thalamocortical neuron model including only the IT channel and the sodium and potassium leak channels. This analysis unveils the dynamics of repetitive burst firing of TC neurons, and describes how the interplay between the amplifying variable mT and the recovering variable hT of the calcium channel IT is sufficient to generate low threshold oscillations in the delta band. We also explored the role of the hyperpolarization activated cationic current Ih in this reduced model and determine that, albeit not required, Ih amplifies and stabilizes the oscillation.

[1]  Yi Zhang,et al.  Genetic Enhancement of Thalamocortical Network Activity by Elevating α1G-Mediated Low-Voltage-Activated Calcium Current Induces Pure Absence Epilepsy , 2009, The Journal of Neuroscience.

[2]  Eugene M. Izhikevich,et al.  Dynamical Systems in Neuroscience: The Geometry of Excitability and Bursting , 2006 .

[3]  John Rinzel,et al.  Synchronization of Electrically Coupled Pairs of Inhibitory Interneurons in Neocortex , 2007, The Journal of Neuroscience.

[4]  German Mato,et al.  The interplay of seven subthreshold conductances controls the resting membrane potential and the oscillatory behavior of thalamocortical neurons. , 2014, Journal of neurophysiology.

[5]  Hee-Sup Shin,et al.  Lack of delta waves and sleep disturbances during non-rapid eye movement sleep in mice lacking α1G-subunit of T-type calcium channels , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Bard Ermentrout,et al.  Simulating, analyzing, and animating dynamical systems - a guide to XPPAUT for researchers and students , 2002, Software, environments, tools.

[7]  D. McCormick,et al.  Functional implications of burst firing and single spike activity in lateral geniculate relay neurons , 1990, Neuroscience.

[8]  David Hansel,et al.  The Role of Intrinsic Cell Properties in Synchrony of Neurons Interacting via Electrical Synapses , 2012 .

[9]  D. McCormick,et al.  Sleep and arousal: thalamocortical mechanisms. , 1997, Annual review of neuroscience.

[10]  Susumu Tonegawa,et al.  Thalamic Cav3.1 T-type Ca2+ channel plays a crucial role in stabilizing sleep. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[11]  R. Traub,et al.  Fast rhythmic bursting can be induced in layer 2/3 cortical neurons by enhancing persistent Na+ conductance or by blocking BK channels. , 2003, Journal of neurophysiology.

[12]  William H. Press,et al.  Numerical Recipes in Fortran 77 , 1992 .

[13]  I. Soltesz,et al.  Low‐frequency oscillatory activities intrinsic to rat and cat thalamocortical cells. , 1991, The Journal of physiology.

[14]  D. McCormick,et al.  A model of the electrophysiological properties of thalamocortical relay neurons. , 1992, Journal of neurophysiology.

[15]  S. Siegelbaum,et al.  Molecular and Functional Heterogeneity of Hyperpolarization-Activated Pacemaker Channels in the Mouse CNS , 2000, The Journal of Neuroscience.

[16]  T. Sejnowski,et al.  Interactions between membrane conductances underlying thalamocortical slow-wave oscillations. , 2003, Physiological reviews.

[17]  Marcelo A. Montemurro,et al.  Linking dynamical and functional properties of intrinsically bursting neurons , 2013, Journal of Computational Neuroscience.

[18]  S. Cruikshank,et al.  Electrical and chemical synapses between relay neurons in developing thalamus , 2010, The Journal of physiology.

[19]  S. Hughes,et al.  Dynamic clamp study of Ih modulation of burst firing and δ oscillations in thalamocortical neurons in vitro , 1998, Neuroscience.

[20]  D. McCormick,et al.  Properties of a hyperpolarization‐activated cation current and its role in rhythmic oscillation in thalamic relay neurones. , 1990, The Journal of physiology.

[21]  Hans-Christian Pape,et al.  Impaired Regulation of Thalamic Pacemaker Channels through an Imbalance of Subunit Expression in Absence Epilepsy , 2005, The Journal of Neuroscience.

[22]  I. Soltesz,et al.  Two inward currents and the transformation of low‐frequency oscillations of rat and cat thalamocortical cells. , 1991, The Journal of physiology.

[23]  Germán Mato,et al.  Synchrony in Excitatory Neural Networks , 1995, Neural Computation.

[24]  R. Miura,et al.  Low-threshold calcium current and resonance in thalamic neurons: a model of frequency preference. , 1994, Journal of neurophysiology.

[25]  Germán Mato,et al.  Electrical Synapses and Synchrony: The Role of Intrinsic Currents , 2003, The Journal of Neuroscience.

[26]  William H. Press,et al.  Numerical Recipes: FORTRAN , 1988 .

[27]  Daesoo Kim,et al.  Lack of the Burst Firing of Thalamocortical Relay Neurons and Resistance to Absence Seizures in Mice Lacking α1G T-Type Ca2+ Channels , 2001, Neuron.

[28]  Frances K. Skinner,et al.  Understanding Activity in Electrically Coupled Networks Using PRCs and the Theory of Weakly Coupled Oscillators , 2012 .

[29]  Javier Cudeiro,et al.  Bursting thalamic responses in awake monkey contribute to visual detection and are modulated by corticofugal feedback , 2014, Front. Behav. Neurosci..

[30]  W. Guido,et al.  Burst and tonic response modes in thalamic neurons during sleep and wakefulness. , 2001, Journal of neurophysiology.

[31]  S. Hughes,et al.  The slow (<1 Hz) rhythm of non-REM sleep: a dialogue between three cardinal oscillators , 2010, Nature Neuroscience.

[32]  R. Llinás,et al.  Ionic basis for the electro‐responsiveness and oscillatory properties of guinea‐pig thalamic neurones in vitro. , 1984, The Journal of physiology.

[33]  T. J. Sejnowski,et al.  Control of slow oscillations in the thalamocortical neuron: a computer model , 1996, Neuroscience.

[34]  A. Destexhe,et al.  Dendritic Low-Threshold Calcium Currents in Thalamic Relay Cells , 1998, The Journal of Neuroscience.

[35]  Inés Samengo,et al.  Type I and Type II Neuron Models Are Selectively Driven by Differential Stimulus Features , 2008, Neural Computation.

[36]  Knut Holthoff,et al.  Absence epilepsy and sinus dysrhythmia in mice lacking the pacemaker channel HCN2 , 2003, The EMBO journal.

[37]  John Rinzel,et al.  Analysis of bursting in a thalamic neuron model , 1994, Biological Cybernetics.