Integrative properties of thalamic neurons

The complex intrinsic properties of thalamocortical (TC) relay neurons, including oscillatory behavior, were modeled based on a series of currents characterized in these neurons: the low-threshold calcium current (IT), a hyperpolarization-activated cation current (Ih) and the regulation of the latter by intracellular Ca2+. The combination of these currents was shown to be sufficient to account for the spectrum of oscillatory and quiescent states in TC neurons [1,2]. A second important player, the thalamic reticular (RE) neuron, also possesses complex intrinsic firing properties which were modeled based on IT and two calcium-activated currents, IK[Ca] and ICAN [3].

In collaboration with Terrence Sejnowski (Salk Institute, USA), Mircea Steriade (Laval University, Canada) and John Huguenard (Stanford University, USA), we developed models of TC and RE neurons that took into account the presence of dendrites and evidenced that high densities of IT in dendrites were necessary to account in detail for the electrophysiological properties of both thalamic reticular [4] and thalamic relay neurons [5]. Contrasting experimental data can be reconciled by the same model if dendritic T-currents are taken into account [5]. Dendritic T-currents also permits thalamic neurons to be switched from burst to tonic mode within a few millisecond, by the presence of synaptic background activity. This predicts that the cortex has the potential to control the state of thalamic circuits within millisecond time scales [4.5].

The specific effect of cortical synapses was also investigated using morphologically-detailed models [6]. The effect of corticothalamic synapses on TC cells was similar to that of afferent synapses, in amplitude, kinetics and timing, although these synapses are located in different regions of the dendrites. This suggests that cortical EPSPs may complement (or predict) the afferent information. In RE cells, high densities of the T-current in dendrites gives an exquisite sensitivity to cortical EPSPs, but only if the dendrites are hyperpolarized. This property has consequences at the level of thalamic circuits, where corticothalamic EPSPs evoke bursts in RE neurons and recruit TC cells predominantly through feedforward inhibition (see Section 3.2). On the other hand, with depolarized dendrites, RE neurons do not generate bursts and the cortical influence on TC cells is mostly excitatory. Models therefore suggest that the cortical influence can either promote or antagonize the relay of information, depending on the state of the dendrites of thalamic reticular neurons [6].

Thus, both simplified models and morphologically-detailed models give important insight to understand the complex, dynamical interactions in thalamic neurons. Models based on morphological reconstructions are useful to understand the role of the current distributions in dendrites on the behavior of the cell. Simplified models account for the most salient electrophysiological properties of thalamic cells, and are more adequate for large-scale network simulations (see Section 3.1 and Section 3.2).

Recently, in collaboration with Thierry Bal (UNIC), we have investigated the responsiveness of thalamic relay neurons under in vivo-like conditions using dynamic-clamp experiments [7]. These experiments (realized by Thierry Bal's team) demonstrated that synaptic noise has a tremendous influence on the "relay" function of thalamic neurons. Thalamic neurons are traditionally viewed as functioning in two distinct modes of firing, the "burst" mode (conferred by the presence of the T-type Ca2+current), and a "tonic" mode where only single spikes are produced, more compatible with the relay function of thalamic neurons. With synaptic noise, however, this duality disappears as bursts and single spikes are produced at all membrane potentials. Interestingly, the probability of generating spikes (combining bursts and single spikes) becomes almost independent of the Vm level in the presence of synaptic noise. The presence of the T-type Ca2+current boosts the response at hyperpolarized levels. This remarkable property is also compatible with a relay function, but only of all spikes are combined. These results suggest that intrinsic neuronal properties influence responsiveness differently in the presence of synaptic noise, and that both intrinsic properties and noise must be taken into account to fully understand the responsiveness of central neurons in physiological conditions [8].

More recently, we showed that the typical transfer function of thalamic neurons in the presence of noise are also compatible with auditory sensory responses observed in vivo [9]. To model auditory responses, it was necessary to take into account the gain modulation of both thalamic and cortical neurons. This shows that how noise affects cellular properties may impact the level of populations of neurons.

[1] Destexhe, A. and Babloyantz, A. A model of the inward current I_h and its possible role in thalamocortical oscillations. NeuroReport 4: 223-226, 1993. (see abstract)

[2] Destexhe, A., Babloyantz, A. and Sejnowski, T.J. Ionic mechanisms for intrinsic slow oscillations in thalamic relay neurons. Biophys. J. 65: 1538-1552, 1993. (see abstract)

[3] Destexhe, A., Contreras, D., Sejnowski, T.J. and Steriade, M. A model of spindle rhythmicity in the isolated thalamic reticular nucleus. J. Neurophysiol. 72: 803-818, 1994. (see abstract)

[4] Destexhe, A., Contreras, D., Steriade, M., Sejnowski, T.J., and Huguenard, J.R. In vivo, in vitro and computational analysis of dendritic calcium currents in thalamic reticular neurons. J. Neuroscience 16: 169-185, 1996. (see abstract)

[5] Destexhe, A., Neubig, M., Ulrich, D. and Huguenard, J.R. Dendritic low-threshold calcium currents in thalamic relay cells. J. Neurosci. 18: 3574-3588, 1998. (see abstract)

[6] Destexhe, A. Modeling corticothalamic feedback and the gating of the thalamus by the cerebral cortex. J. Physiol. (Paris) 94: 391-410, 2000. (see abstract)

[7] Wolfart, J., Debay, D., Le Masson, G., Destexhe, A. and Bal, T. Synaptic background activity controls spike transfer from thalamus to cortex. Nature Neuroscience 8: 1760-1767, 2005 (see abstract)

[8] Destexhe, A. 20 years of "noise" - Contributions of computational neuroscience to the exploration the effect of background activity on central neurons. In: 20 years of Computational Neuroscience, Edited by Bower J, Springer, New York, pp. 167-186, 2013 (see abstract)

[9] Reig, R., Zerlaut, Y., Vergara, R., Destexhe, A. and Sanchez-Vives, M. Gain modulation of synaptic inputs by network state in auditory cortex in vivo. Journal of Neuroscience 35: 2689-2702, 2015 (see abstract)

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