We have shown that a subset of neurons in anterodorsal thalamic nucleus exhibit graded increases in firing rate in response to repeated hyperpolarizing pulses. The increase can be sustained up to several minutes while the firing rate decays gradually. Depolarization is not as effective as hyperpolarization in controlling persistent activity. Although depolarizing pulses lead initially to a faster decay of firing rate, they have little influence on the final firing rate after the pulses terminate. We have also observed a serotonin-dependent enhancement of the hyperpolarization-induced increase in firing rate.
studies in freely behaving rats show that ~60% of the cells recorded from anterodorsal thalamus are head-direction cells [29
]. In our experiments, about 53% (40/76) of the cells recorded exhibited graded persistent firing, and these cells also showed little firing rate accommodation. The remaining cells did not exhibit graded persistent firing and they all showed a high degree of firing rate accommodation. Given that most neurons in the anterodorsal thalamus in the rat are principal neurons [17
], further studies are required to correlate the morphology of the cells with the functional property of persistent firing.
The hyperpolarization-induced graded increase in firing rate reported in this study differs from the depolarization-induced persistent activity in entorhinal cortex [9
], amygdala [10
], and postsubiculum [36
]. In the latter cases, the persistent firing was induced by depolarization instead of hyperpolarization, and it appeared much more stable, without any tendency for spontaneous decay, at least on the time scale of many minutes. Our phenomenon is also different from firing rate potentiation in the vestibular nucleus, which does not exhibit graded levels of firing rate [16
]. We have confirmed directly that under conditions similar to the original reports, the thalamic neurons in our preparations do not exhibit the persistent activities described in [9
] or [16
The phenomenon we observed in the thalamus is similar but not identical to the hyperpolarization-induced graded persistent activity in the prefrontal cortex [34
]. One difference is that the thalamic persistent firing tends to decay spontaneously whereas the prefrontal cortical persistent firing appears much more stable. Another difference is that depolarizing pulses can completely turn off the persistent firing in the prefrontal cortex, whereas in anterodorsal thalamus we have not observed this effect.
The goal of this paper is to demonstrate the existence of single-cell persistent activity in a component of the head-direction system: the anterodorsal thalamus. Although the exact mechanism of the thalamic graded persistent activity is unknown and beyond the scope of this paper, several general mechanisms for single-cell persistent activities have been proposed elsewhere [11
]. For example, calcium-dependent nonspecific cation channels are implicated in the persistent activity in the entorhinal cortex [9
] and the postsubiculum [36
]. The persistent firing in prefrontal cortex may involve hyperpolarization-activated cation channels (Ih
) and other mechanisms [34
]. For comparison, the anterodorsal thalamus also has Ih
current, which can be enhanced by serotonin [4
]. Since single-cell persistent activity has been found in the anterodorsal thalamus and the postsubiculum [36
] which is downstream from the thalamus, one should also look for this phenomenon upstream in the mammillary body [2
]. One should also compare with other thalamic nuclei including the neighboring anteroventral nucleus [7
], and test the effects of other neuromodulators besides serotonin [14
How could the single-cell persistent activity observed in this and other previous studies be useful for the head-direction system? The thalamic head-direction cells observed in freely moving animals can have a peak firing rate as high as ~100 Hz, and the activity can change rapidly with the animal’s head movement [29
]. By contrast, the single-cell persistent activity observed in this study saturates at ~15Hz and tends to be sluggish (). Similarly, the persistent activity in postsubiculum does not reach a high firing rate, although it can be triggered by a short stimulus that induces only a few spikes [36
]. Because of the low firing rate, the single-cell persistent activity might not be the main mechanism responsible for the firing around the peak of the directional tuning curve of a head-direction cell, especially those with high peak firing rates. This observation, however, does not rule out the possibility that the thalamic neurons that exhibit persistent activity in slice preparations may still behave as head-direction cells in vivo
. We found that the thalamic neurons exhibiting hyperpolarization-induced single-cell persistent activity can fire at much higher rates during rebound or when injected with depolarizing current. Therefore, a thalamic head-direction cell, driven by depolarizing synaptic current around the peak of its tuning curve, might switch to persistent activity mode at a low firing rate when the animal’s head is away from the preferred direction. How suitable hyperpolarization could be generated in in vivo
condition is unclear, but presumably it could come from inhibitory interneurons in the thalamus and the reticular nucleus during certain sequences of head movements. We emphasize that the persistent activity at low firing rate can still be important for the peak firing of head-direction cells, because the preferred directions of different cells are known to be rigidly coupled. Stabilizing any subset of these cells should help stabilizing the whole system. The slow time scale of the persistent activity could potentially make the system more stable and more resistant to activity drift.