The Low Threshold Calcium Spike
The low threshold calcium spike (LTS) is a hallmark of thalamocortical (TC) and thalamic reticular nucleus (TRN) neurons. Although it has been known for a number of years that LTS depend on T-type voltage gated calcium channels the precise mechanism underlying the ability of these neurons to produce LTS has remained unknown. Previous work, including our own (Errington et al., 2010, 2012) suggested that much of the T-conductance underlying the LTS was found in the dendrites of TC and TRN neurons. Therefore we asked the question: how do these dendritic T channels produce the LTS? If the T channels are located in the dendrites it is logical to predict that LTS might be initiated locally in the dendrites before spreading to the soma as occurs with voltage gated calcium channel dependent spikes in the apical dendrite of cortical pyramidal neurons. On the other hand, action potentials, mediated by voltage gated sodium channels, typically initiate in the axon initial segment close to the soma before backpropagating either actively or passively into the dendritic tree. The answer to this question could only be obtained by recording the membrane potential in the dendrites of TC and TRN neurons during the LTS. By targeting dendrites using 2-photon fluorescence, we were able, for the first time, to make recordings directly from the thin dendrites of TC neurons (up to the tip ~ 160 um) and TRN (up to 200 um form the soma).
Simulation of somatic and dendritic membrane potential during the LTS in a thalamocortical neuron.
We have used the Neuron simulation environment to produce a multi-compartmental model of a dorsal lateral geniculate thalamocortical neuron. This model was based on new data obtained by performing dendritic patch clamp recordings and accurately reproduces the firing and synaptic integration properties of thalamocortical neurons. The model was used in our papers published in The Journal of Neuroscience (Connelly et al., 2015, 2016) and can be found at the ModelDB repository.
Simulation of the somatic and dendritic membrane potential during a tonic action potential in a thalamocortical neuron (slowed down relative to the LTS above).