Variability of quantal synaptic currents in thalamocortical neurons.

Broad amplitude variability and skewed distributions are characteristic features of quantal synaptic currents (minis) at central synapses. The relative contributions of the various underlying sources are still debated. Through computational models of thalamocortical neurons, we separated intra- from extra-synaptic sources. Our simulations indicate that the external factors of local input resistance and dendritic filtering generate equally small amounts of negatively skewed synaptic variability. The ability of these two factors to reduce positive skew increased as their contribution to variability increased, which in control trials for morphological, biophysical, and experimental parameters never exceeded 10% of the range. With these dendritic factors ruled out, we tested multiple release models, which led to distributions with clearly non-physiological multiple peaks. We conclude that intra-synaptic organization is the primary determinant of synaptic variability in thalamocortical neurons and, due to extra-synaptic mechanisms, is more potent than the data suggested. Thalamortical neurons, especially in rodents, constitute a remarkably favorable system for molecular genetic studies of synaptic variability and its functional consequence.

Dendritic low-threshold calcium currents in thalamic relay cells.

The low-threshold calcium current (IT) underlies burst generation in thalamocortical (TC) relay cells and plays a central role in the genesis of synchronized oscillations by thalamic circuits. Here we have combined in vitro recordings and computational modeling techniques to investigate the consequences of dendritically located IT in TC cells. Simulations of a reconstructed TC cell were compared with the recordings obtained in the same cell to constrain the values of its passive parameters. T-current densities in soma and proximal dendrites were then estimated by matching the model to voltage-clamp recordings obtained in dissociated TC cells, which lack most of the dendrites. The distal dendritic T-current density was constrained by recordings in intact TC cells, which show 5-14 times larger peak T-current amplitudes compared with dissociated cells. Comparison of the model with the recordings of the same cell constrained further the T-current density in dendrites, which had to be 4.5-7.6 times higher than in the soma to reproduce all experimental results. Similar conclusions were reached using a simplified three-compartment model. Functionally, the model shows that the same amount of T-channels can lead to different bursting behaviors if they are exclusively somatic or distributed throughout the dendrites. In conclusion, this combination of models and experiments shows that dendritic T-currents are necessary to reproduce low-threshold calcium electrogenesis in TC cells. Dendritic T-current may also have significant functional consequences, such as an efficient modulation of thalamic burst discharges by corticothalamic feedback.