GABAergic interneurons (INs) in the dorsal lateral geniculate nucleus (dLGN) shape the information flow from retina to cortex, presumably by controlling the number of visually evoked spikes in geniculate thalamocortical (TC) neurons, and refining their receptive field. The INs exhibit a rich variety of firing patterns: Depolarizing current injections to the soma may induce tonic firing, periodic bursting or an initial burst followed by tonic spiking, sometimes with prominent spike-time adaptation. When released from hyperpolarization, some INs elicit rebound bursts, while others return more passively to the resting potential. A full mechanistic understanding that explains the function of the dLGN on the basis of neuronal morphology, physiology and circuitry is currently lacking. One way to approach such an understanding is by developing a detailed mathematical model of the involved cells and their interactions. Limitations of the previous models for the INs of the dLGN region prevent an accurate representation of the conceptual framework needed to understand the computational properties of this region. We here present a detailed compartmental model of INs using, for the first time, a morphological reconstruction and a set of active dendritic conductances constrained by experimental somatic recordings from INs under several different current-clamp conditions. The model makes a number of experimentally testable predictions about the role of specific mechanisms for the firing properties observed in these neurons. In addition to accounting for the significant features of all experimental traces, it quantitatively reproduces the experimental recordings of the action-potential- firing frequency as a function of injected current. We show how and why relative differences in conductance values, rather than differences in ion channel composition, could account for the distinct differences between the responses observed in two different neurons, suggesting that INs may be individually tuned to optimize network operation under different input conditions.

Highlights d V1 layer 6 corticothalamic neurons were imaged during different behavioral states d L6CT neurons are either visual stimulus activated (VSA), suppressed (VSS), or quiet d Activity of VSA and VSS neurons complement each other to a constant level d Complementary VSA and VSS neuron activity level is behavioral state dependent

Dendritic NMDA spike/plateau potentials, first discovered in cortical pyramidal neurons, provide supralinear integration of synaptic inputs on thin and distal dendrites, thereby increasing the impact of these inputs on the soma. The more specific functional role of these potentials has been difficult to clarify, partly due to the complex circuitry of cortical neurons. Thalamocortical (TC) neurons in the dorsal lateral geniculate nucleus participate in simpler circuits. They receive their primary afferent input from retina and send their output to visual cortex. Cortex, in turn, regulates this output through massive feedback to distal dendrites of the TC neurons. The TC neurons can operate in two modes related to behavioral states: burst mode prevailing during sleep, when T-type calcium bursts largely disrupt the transfer of signals from retina to cortex, and tonic mode, which provides reliable transfer of retinal signals to cortex during wakefulness. We studied dendritic potentials in TC neurons with combined two-photon calcium imaging and whole-cell recording of responses to local dendritic glutamate iontophoresis in acute brain slices from mice. We found that NMDA spike/plateaus can be elicited locally at distal dendrites of TC neurons. We suggest that these dendritic potentials have important functions in the cortical regulation of thalamocortical transmission. NMDA spike/plateaus can induce shifts in the functional mode from burst to tonic by blockade of T-type calcium conductances. Moreover, in tonic mode, they can facilitate the transfer of retinal signals to cortex by depolarization of TC neurons.

An optimal visual stimulus flashed on the receptive field of a retinal ganglion cell typically evokes a strong transient response followed by weaker sustained firing. Thalamocortical (TC) neurons in the dorsal lateral geniculate nucleus, which receive their sensory input from retina, respond similarly except that the gain, in particular of the sustained component, changes with level of arousal. Several lines of evidence suggest that retinal input to TC neurons through NMDA receptors plays a key role in generation of the sustained response, but the mechanisms for the state-dependent variation in this component are unclear. We used a slice preparation to study responses of TC neurons evoked by trains of electrical pulses to the retinal afferents at frequencies in the range of visual responses in vivo. Despite synaptic depression, the pharmacologically isolated NMDA component gave a pronounced build-up of depolarization through temporal summation of the NMDA receptor mediated EPSPs. This depolarization could provide sustained firing, the frequency of which depended on the holding potential. We suggest that the variation of sustained response in vivo is caused mainly by the state-dependent modulation of the membrane potential of TC neurons which shifts the NMDA receptor mediated depolarization closer to or further away from the firing threshold. The pharmacologically isolated AMPA receptor EPSPs were rather ineffective in spike generation. However, together with the depolarization evoked by the NMDA component, the AMPA component contributed significantly to spike generation, and was necessary for the precise timing of the generated spikes.