Abstract
The thalamus has been implicated in fear extinction, yet the role of the thalamic reticular nucleus (TRN) in this process remains unclear. Here, in mice, we show that the rostroventral part of the TRN (TRNrv) is critically involved in the extinction of tone-dependent fear memory. Optogenetic excitation of TRNrv neurons during extinction learning dramatically facilitated, whereas the inhibition disrupted, the fear extinction. Single unit recordings demonstrated that TRNrv neurons selectively respond to conditioned stimuli but not to neutral stimuli. TRNrv neurons suppressed the spiking activity of the medial part of the dorsal midline thalamus (dMTm), and a blockade of this inhibitory pathway disrupted fear extinction. Finally, we found that the suppression of dMTm projections to the central amygdala promotes fear extinction, and TRNrv neurons have direct connections to this pathway. Our results uncover a previously unknown function of the TRN and delineate the neural circuit for thalamic control of fear memory.
Highlights
The thalamus has been implicated in fear extinction, yet the role of the thalamic reticular nucleus (TRN) in this process remains unclear
Recent studies showed that the dorsal midline thalamus, which includes the paraventricular nucleus of the thalamus (PVT) and the mediodorsal thalamic nucleus (MD)[3,16], plays a critical role in persistent attenuation of fear[3], whereas it is not involved in fear conditioning[16]
To define finer connectivity between the rostral part of the TRN and the dorsal midline thalamus (dMT), we simultaneously injected two different retrograde tracers: fluorogold (FG) into the medial part of the dMT, which covers the PVT and the medial part of the MD (Fig. 1f), and cholera toxin-B subunit (CTB) into the lateral part of the dMT, which covers the lateral part of the MD and the centrolateral thalamic nucleus (CL) (Fig. 1e–i)
Summary
The thalamus has been implicated in fear extinction, yet the role of the thalamic reticular nucleus (TRN) in this process remains unclear. As the first step to explore the role of the TRN in fear extinction, we identified that the rostroventral part of the TRN (TRNrv) distinctly projects to the medial part of the dMT (dMTm) which was previously implicated in persistent attenuation of fear[3] Guided by this connection map, we carried out circuit analysis and found that TRNrv neurons are activated during extinction learning. We demonstrate that the suppression of the dMTm projections to the central amygdala (CeA) promotes fear extinction and that TRNrv neurons have direct synaptic connections to this dMTm–CeA circuit These results show the critical role of the TRN in fear extinction and reveal a novel neural pathway underlying fear extinction
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