State-dependent firing determines intrinsic dendritic Ca2+ signaling in thalamocortical neurons

Activity-dependent dendritic Ca2+ signals play a critical role in multiple forms of nonlinear cellular output and plasticity. In thalamocortical neurons, despite the well established spatial separation of sensory and cortical inputs onto proximal and distal dendrites, respectively, little is known about the spatiotemporal dynamics of intrinsic dendritic Ca2+ signaling during the different state-dependent firing patterns that are characteristic of these neurons. Here we demonstrate that T-type Ca2+ channels are expressed throughout the entire dendritic tree of rat thalamocortical neurons and that they mediate regenerative propagation of low threshold spikes, typical of, but not exclusive to, sleep states, resulting in global dendritic Ca2+ influx. In contrast, actively backpropagating action potentials, typical of wakefulness, result in smaller Ca2+ influxes that can temporally summate to produce dendritic Ca2+ accumulations that are linearly related to firing frequency but spatially confined to proximal dendritic regions. Furthermore, dendritic Ca2+ transients evoked by both action potentials and low-threshold spikes are shaped by Ca2+ uptake by sarcoplasmic/endoplasmic reticulum Ca2+ ATPases but do not rely on Ca2+-induced Ca2+ release. Our data demonstrate that thalamocortical neurons are endowed with intrinsic dendritic Ca2+ signaling properties that are spatially and temporally modified in a behavioral state-dependent manner and suggest that backpropagating action potentials faithfully inform proximal sensory but not distal corticothalamic synapses of neuronal output, whereas corticothalamic synapses only “detect” Ca2+ signals associated with low-threshold spikes