Reciprocal inhibition and slow calcium decay in perigeniculate interneurons explain changes of spontaneous firing of thalamic cells caused by cortical inactivation

Abstract

The role of cortical feedback in the thalamocortical processing loop has been extensively investigated over the last decades. With an exception of several cases, these searches focused on the cortical feedback exerted onto thalamo-cortical relay (TC) cells of the dorsal lateral geniculate nucleus (LGN). In a previous, physiological study, we showed in the cat visual system that cessation of cortical input, despite decrease of spontaneous activity of TC cells, increased spontaneous firing of their recurrent inhibitory interneurons located in the perigeniculate nucleus (PGN). To identify mechanisms underlying such functional changes we conducted a modeling study in NEURON on several networks of point neurons with varied model parameters, such as membrane properties, synaptic weights and axonal delays. We considered six network topologies of the retino-geniculo-cortical system. All models were robust against changes of axonal delays except for the delay between the LGN feed-forward interneuron and the TC cell. The best representation of physiological results was obtained with models containing reciprocally connected PGN cells driven by the cortex and with relatively slow decay of intracellular calcium. This strongly indicates that the thalamic reticular nucleus plays an essential role in the cortical influence over thalamo-cortical relay cells while the thalamic feed-forward interneurons are not essential in this process. Further, we suggest that the dependence of the activity of PGN cells on the rate of calcium removal can be one of the key factors determining individual cell response to elimination of cortical input.

Fig. 1

Activity of the dissociated model cells (outside of the network, stimulated by current injection) used in the study (a) tonic mode of TC cell in response to depolarization and hyperpolarization currents (b) bursting activity of PGN cell in response to hyperpolarization current (PGN model cell did not exhibit tonic activity) (c) activity of feed-forward interneuron (Int) in response to depolarizing current (d) activity of cortical (Cx) cell in response to depolarizing current

Fig. 2

Network topologies of the studied models of cortico-thalamic circuitry (a) Model I: Simple thalamo-cortical loop (b) Model II by Wörgötter et al. (1998) (c) Model III by Debay et al. (2001) (d) Model IV by Einevoll and Plesser (2002) (e) Model V by Hillenbrand and van Hemmen (2001) (f) Model VI by Ahlsen et al. (1985). Large circles – cells, small circles – synapses. White symbols – excitatory elements, black symbols inhibitory elements. Broken line – reciprocal inhibition between PGN cells, Ret – retinal ganglion cell, LGN – principal LGN cell, Int – feed-forward interneuron, PGN – recurrent interneuron, Cx – cortical cell

Fig. 3

Stability of Model VI in two-dimensional space where the weights of connections from PGN to PGN and from TC to PGN are changed. Small dots denote negative samples, larger circles – positive samples (consistent with experiment). The square marks the parameters values shown in Table 5

Fig. 4

Firing rates of TC and PGN cells calculated for Model VI with different retinal input frequencies. The differences in firing rates between states with active and inactive cortex were significant at input frequencies over 10 Hz (p > 0.01; one tailed t-test)

Fig. 5

The effect of elimination of Cx–PGN connection on TC firing rate in Model VI. Elimination of cortical input to PGN makes TC cells insensitive to changes of cortical input. Synaptic weights from the cortex in Model VI and its variant with eliminated Cx–PGN connection were reduced by 20, 50 and 75 % or increased by 20, 50, 75 and 100 % with respect to the original settings

Fig. 6

Dependence of firing rate of depolarized, dissociated PGN model cell on the time constant of calcium removal rate (τ_Ca). Decrease of the time constant from 200 ms to 50 ms increased the number of spikes in the bursts, shortened interburst intervals, and finally led to persistent firing, when set at 30 ms

Fig. 7

The effect of calcium removal rate on firing frequency of TC and PGN cells in Model VI. The slower calcium removal in PGN cell the higher the difference between firing frequencies of PGN and TC cells before and after elimination of cortical input. Retinal input: 50 Hz