Distinct burst properties contribute to the functional diversity of thalamic nuclei

Abstract

Thalamic neurons fire spikes in two modes, burst and tonic. The function of burst firing is unclear, but the evidence suggests that bursts are more effective at activating cortical cells, and that postinhibition rebound bursting contributes to thalamocortical oscillations during sleep. Bursts are considered stereotyped signals; however, there is limited evidence regarding how burst properties compare across thalamic nuclei of different functional or anatomical organization. Here, we used whole-cell patch clamp recordings and compartmental modeling to investigate the properties of bursts in six sensory thalamic nuclei, to study the mechanisms that can lead to different burst properties, and to assess the implications of different burst properties for thalamocortical transmission and oscillatory functions. We found that bursts in higher-order cells on average had higher number of spikes and longer latency to the first spike. Additionally, burst features in first-order neurons were determined by sensory modality. Shifting the voltage-dependence and density of the T-channel conductance in a compartmental model replicates the burst properties from the intracellular recordings, pointing to molecular mechanisms that can generate burst diversity. Furthermore, the model predicts that bursts with higher number of spikes will drastically reduce the effectiveness of thalamocortical transmission. In addition, the latency to burst limited the rebound oscillatory frequency in modeled cells. These results demonstrate that burst properties vary according to the thalamocortical hierarchy and with sensory modality. The findings imply that, while in burst mode, thalamocortical transmission and firing frequency will be determined by the number of spikes and latency to burst.

Keywords: burst; first order; higher order; oscillation; sensory; thalamocortical; thalamus.

FIGURE 1

Number of spikes in bursts evoked by hyperpolarization of TC cells in different nuclei. (a) Cells were recorded in current clamp and injected with step pulses to evoke rebound bursts. (b) For each burst, we quantified the number of spikes and time‐dependent features like latency to spike and inter‐spike interval (see Section 2 for details). (c) Examples of bursts from six thalamic cells from different nuclei show different number of spikes/burst at similar hyperpolarization level prior to the burst across the cells (average − 90.92 ± 0.90 mV sd). (d) Distributions of number of spikes/burst (jittered to help visualization of individual data points) for all bursts across the population of thalamic cells in first‐order (blue) and higher‐order (red) nuclei. Boxes indicate the median and 25%–75% quartiles. dLGN, dorsal lateral geniculate nucleus; dMGB, dorsal medial geniculate body; LP, lateral posterior nucleus; POm, posterior medial nucleus; vMGB, ventral medial geniculate body; VP, ventral posterior nucleus [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 2

Number of spikes per burst at increasing hyperpolarization levels. Each line represents data from one cell (jittered in y‐axis); zero in the x‐axis corresponds to the least hyperpolarized pulse that led to a burst, and subsequent points indicate more hyperpolarized pulses with respect to this zero level. Each panel contains cells from six different nuclei (first order—(a) dLGN, (b) vMGB, (c) VP and higher order—(d) LP, (e) dMGB, (f) POm). Yellow lines represent cells for which the number of spikes per burst were constant irrespective of the hyperpolarization level, and green lines represent cells for which the number of spikes per burst varied with hyperpolarization. The number of cells in each nucleus belonging to one of the two types is included in the textbox on the top‐right corner of each panel. Note that the range of the x‐ and y‐axes was adjusted for each nucleus and is not same in all panels. dLGN, dorsal lateral geniculate nucleus; dMGB, dorsal medial geniculate body; LP, lateral posterior nucleus; POm, posterior medial nucleus; vMGB, ventral medial geniculate body; VP, ventral posterior nucleus [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 3

Increase in within‐burst spike frequency with hyperpolarization. (a) Example bursts (from two VP cells) showing an increase in the spike rate with hyperpolarization (dotted lines), irrespective of the number of spikes per burst increasing (cell in green) or remaining constant (cell in yellow) with hyperpolarization. (b–e) Each line represents the frequency of the first intra‐burst spike interval for one cell, at increasing hyperpolarization levels from the first level that produced a burst. Panels contain data for cells from four different nuclei—(b) LP, (c) dMGB, (d) POm, (e) VP. Note that the range of the x‐axis is not same in all panels. (f) We found no statistical difference in the frequency across nuclei (LP, dMGB, VP and POm; dLGN and vMGB were not included in this analysis because of low number of spikes per bursts). Blue = FO; red = HO. (g) Distributions of spike frequency adaptation between last and first intra‐burst intervals for cells with at least four spikes/burst show POm having lower adaptation compared to other two HO nuclei. dLGN, dorsal lateral geniculate nucleus; dMGB, dorsal medial geniculate body; LP, lateral posterior nucleus; POm, posterior medial nucleus; vMGB, ventral medial geniculate body; VP, ventral posterior nucleus [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 4

Latencies to burst reach higher values in higher‐order (HO) nuclei and dorsal lateral geniculate nucleus (dLGN). (a) Bursts evoked from similar hyperpolarization levels in two cells of the auditory (left) and somatosensory (right) systems display short latency in first‐order (FO) nuclei and longer latency in the corresponding HO. (b) Population distribution of the latency values for all evoked bursts. (c) Lines represent burst latencies at different hyperpolarization levels for each cell in FO (blue) and HO (red) nuclei in visual (i), auditory (ii) and somatosensory (iii) systems and show a decrease in latency with increased hyperpolarization. Insets show exponential fits for each of the cells in the raw data plots, with the average of the fits shown by darker blue and red lines (average R ² for fits in the insets: (i) .97 ± .04, (ii) .99 ± .01, (iii) .98 ± .05). Note the difference in latencies between FO and HO at every level of hyperpolarization in auditory and somatosensory systems. (d) A negative correlation was observed in the plots of latency against number of spikes per burst for FO and HO nuclei (R ² indicates goodness‐of‐fit for a linear model). Blue = FO; red = HO [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 5

No correlation between latency and decay time constant. (a) Distribution of decay time constant across all the nuclei (see text for details). Blue = FO; red = HO. (b) No correlation between decay time constant and latency (correlation coefficient r = −.18) [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 6

T current kinetics replicate burst properties of first‐order (FO) and higher‐order (HO) neurons. (a) Compartmental model of a thalamocortical cell reproduces tonic and burst modes of response (yellow trace after removing the T current). (b) Activation (green) and inactivation (magenta) curves used in the model were shifted in the x‐axis (voltage dependence) to test their effect on burst properties. (c) T current evoked after hyperpolarization to −84 mV at different values of V _shift; note the decrease in amplitude and longer delay in the T current peak with larger shifts. (d) Burst results obtained with different combinations of V _shift values (columns) and different maximum T conductance values (rows). The color code indicates simulations that replicate bursts observed in FO (blue) and HO (red) cells. s = spikes/burst; l = latency. (e) Shifting the inactivation curve to a more hyperpolarized level (gray line) led to no burst. Other curves represent the inactivation curve shifted to a more depolarized level. V _shift values represent the additional amount by which inactivation curves are shifted compared to the activation curve. (f) T current evoked after hyperpolarizing the model to −83 mV when the inactivation curve was shifted by different amounts; note the increase in amplitude with larger shifts. (g) Simulation results for a particular g _T and M _∞: V _shift showed that increasing the relative H _∞ V _shift led to an increase in spikes/burst. Only the initial shifts in H _∞ led to a decrease in latency. s = spikes/burst; l = latency [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 7

Intrinsic properties and age in first‐order (FO) and higher‐order (HO) neurons. (a) Population distributions of age (postnatal days), membrane capacitance (Cm, in picoFarads) and membrane resistance (Rm, in MegaOhms); 0 = dLGN, 1 = LP, 2 = vMGB, 3 = dMGB, 4 = VP, 5 = POm. (b) Age (left), membrane capacitance (middle) and membrane resistance (right) in relation to the number of spikes per burst and the latency for FO cells (in all plots, each dot represents data from one cell). (c) Same for HO cells. dLGN, dorsal lateral geniculate nucleus; dMGB, dorsal medial geniculate body; LP, lateral posterior nucleus; POm, posterior medial nucleus; vMGB, ventral medial geniculate body; VP, ventral posterior nucleus [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 8

Sag voltage does not explain the diversity of burst properties and correlates with latency in both first‐order (FO) and higher‐order (HO) nuclei. (a) The sag voltage was quantified by calculating the difference between the minimum membrane voltage at the start of the hyperpolarization pulse (≤125 ms) and at 250 ms after that minimum. Green trace is an example of no sag. (b) Distributions of sag voltages (in pulses between −85 and − 95 mV in the initial 125 ms of current injection) compared across the six nuclei. 0 = dLGN, 1 = LP, 2 = vMGB, 3 = dMGB, 4 = VP, 5 = POm. (c) Number of spikes per burst versus sag voltages for FO cells shows no correlation between the two quantities. (d) Latency versus sag voltages in FO cells shows an inverse correlation; black line is an exponential fit. (di,ii,iii) show the correlation between sag and latency for the individual nuclei. Sag for burst properties analyses was calculated from pulses with similar hyperpolarization immediately before the burst (−75 to −85 mV). Cells with no sag are not shown in the plots. (e) and (f) same as (c) and (d) for HO nuclei. (g, h) Simulations in the compartmental thalamic model showed that increasing g_A led to a decrease in the number of spikes/burst (g) and to an increase in latency (h). dLGN, dorsal lateral geniculate nucleus; dMGB, dorsal medial geniculate body; LP, lateral posterior nucleus; POm, posterior medial nucleus; vMGB, ventral medial geniculate body; VP, ventral posterior nucleus [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 9

Number of spikes per burst significantly reduces the probability of release at thalamocortical terminals. (a) Example simulation showing the release probability over time after a burst that mimics the features obtained from a recorded thalamocortical (TC) cell; release probability values were obtained at the time indicated by the arrow (following 100 ms plus the latency obtained from all evoked bursts). (b) Distribution of release probabilities obtained after simulations that mimic spikes per burst and latencies in all recorded nuclei. (c, d) Distribution of release probabilities using only the values of spikes per burst (release probability estimated at 100 ms). (e, f) Distribution of release probabilities using only latency values from the in vitro data and after a burst with only one spike. Blue = FO; red = HO. (g) Linear correlation between excitatory postsynaptic potential (EPSP) amplitude and the synapse's release probability from simulations in a thalamocortical model that contacts a pyramidal cell (green) or an interneuron (yellow). (h, i) Effect of a TC spike on EPSP amplitude (mV) in two types of cortical cells (interneuron and pyramidal) simulated at different synaptic release probabilities observed in the simulations in (b) [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 10

Latency to burst sets a cutoff frequency for rebound bursting in thalamic neurons. (a) Example simulation in which the TC model cell receives 50 ms negative current pulses at 1 Hz (left) or 14 Hz (right). (b) Latency values obtained at progressively larger V _shift. Dashed lines indicate the values selected for the simulations in (c). (c) Fraction of inhibitory pulses applied at increasing frequencies that result in a burst; increasing V _shift values (color coded) result in progressively lower cutoff frequencies [Color figure can be viewed at wileyonlinelibrary.com]