Dissociable encoding of motivated behavior by parallel thalamo-striatal projections

SUMMARY The successful pursuit of goals requires the coordinated execution and termination of actions that lead to positive outcomes. This process is thought to rely on motivational states that are guided by internal drivers, such as hunger or fear. However, the mechanisms by which the brain tracks motivational states to shape instrumental actions are not fully understood. The paraventricular nucleus of the thalamus (PVT) is a midline thalamic nucleus that shapes motivated behaviors via its projections to the nucleus accumbens (NAc)1–8 and monitors internal state via interoceptive inputs from the hypothalamus and brainstem3,9–14. Recent studies indicate that the PVT can be subdivided into two major neuronal subpopulations, namely PVTD2(+) and PVTD2(−), which differ in genetic identity, functionality, and anatomical connectivity to other brain regions, including the NAc4,15,16. In this study, we used fiber photometry to investigate the in vivo dynamics of these two distinct PVT neuronal types in mice performing a reward foraging-like behavioral task. We discovered that PVTD2(+) and PVTD2(−) neurons encode the execution and termination of goal-oriented actions, respectively. Furthermore, activity in the PVTD2(+) neuronal population mirrored motivation parameters such as vigor and satiety. Similarly, PVTD2(−) neurons, also mirrored some of these parameters but to a much lesser extent. Importantly, these features were largely preserved when activity in PVT projections to the NAc was selectively assessed. Collectively, our results highlight the existence of two parallel thalamo-striatal projections that participate in the dynamic regulation of goal pursuits and provide insight into the mechanisms by which the brain tracks motivational states to shape instrumental actions.

(I) Left: Density estimates plots for trials during pPVT D2(+) neuronal imaging and sorted by approach latency blocks.Right: Trial distribution for those trials performed during pPVT D2(+) neuronal imaging showing proportion of trials in approach latency blocks and their distribution across trial group blocks.
(J) Left: Density estimates graphs for trials during pPVT D2(+) neuronal imaging and sorted by trial group blocks.Right: Trial distribution for those trials performed during pPVT D2(+) neuronal imaging showing proportion of trials in trial group blocks and their distribution across approach latency blocks.
All data in the figure are shown as mean ±s.e.m. 2. In vivo dynamics of PVT D2(+) and PVT D2(-) neurons during cue presentation and during reward omission testing session.
(E) Left: Average pPVT D2(+) neuronal GCaMP6s responses when mice entered the food port but were not rewarded.Right: AUC quantification of the reward omission-evoked changes in GCaMP6s fluorescence in pPVT D2(+) neurons.Two-tailed paired t-test, p=0.24; ns, not significant.
(F) Left: Latencies to reach the reward zone across trial group blocks.Repeated measures ANOVA, p=0.26; ns, not significant.Middle: Average pPVT D2(+) GCaMP6s responses during approach in the OM session for early and late trials.Right: AUC quantification of pPVT D2(+) GCaMP6s activity in the OM session for trial group blocks.
105 and is also made available for use under a CC0 license.
(which was not certified by peer review) is the author/funder.This article is a US Government work.It is not subject to copyright under 17 USC The copyright holder for this preprint this version posted January 21, 2024.; https://doi.org/10.1101/2023.07.07.548113 doi: bioRxiv preprint (G) Same as (F) but for pPVT D2(+) during reward omission.Repeated measures ANOVA, p=0.44; ns, not significant.
(H) Left: Latencies to reach the reward zone in seconds for each approach latency block during the reward omission session.Repeated measures ANOVA, **p<0.0001.Middle: Average pPVT D2(+) neuronal GCaMP6s responses for fast and slow reward approach in the OM session.The red line indicates 20-80% of the slope of the line.Right: In the OM session, slope-of-the-line quantifications of pPVT D2(+) neuronal GCaMP6s activity across approach latency blocks.Repeated measures ANOVA, **p<0.01.
(L) Same as (K) but grouped by trial group blocks.Repeated measures ANOVA, p=0.50; ns, not significant.
105 and is also made available for use under a CC0 license.
(which was not certified by peer review) is the author/funder.This article is a US Government work.It is not subject to copyright under 17 USC The copyright holder for this preprint this version posted January 21, 2024.; https://doi.org/10.1101/2023.07.07.548113 doi: bioRxiv preprint (C) Same as (A) but for photometric responses of pPVT D2(-) neuron.No association between pPVT D2(-) GCaMP6s responses and approach latency at cue presentation (left) or at reward zone entry (right).
(D) Same as (B) but for photometric responses of pPVT D2(-) neuron.No association between pPVT D2(-) GCaMP6s responses and trial order at cue presentation (left) nor at reward zone entry (right).
(E) Same as (A) but for photometric responses of aPVT D2(-) neurons.No association between aPVT D2(-) GCaMP6s responses and approach latency at cue presentation (left) or at reward zone entry (right).
(F) Same as (B) but for photometric responses of aPVT D2(-) neurons.No association between aPVT D2(-) GCaMP6s responses and trial order at cue presentation (left) nor at reward zone entry (right).
(G) FLMM coefficient estimates plots applying 'recording location' (i.e., aPVT or pPVT) as a covariate and showing statistical significance at each trial time-point results for the photometric responses of PVT D2(-) neurons for cue presentation and reward zone entry.
(H) FLMM coefficient estimates plots of the return latency effect and statistical significance at each trial time-point results for the photometric responses of pPVT D2(+) neurons for trial termination and trigger zone entry.No association between pPVT D2(+) 105 and is also made available for use under a CC0 license.
(which was not certified by peer review) is the author/funder.This article is a US Government work.It is not subject to copyright under 17 USC The copyright holder for this preprint this version posted January 21, 2024.; https://doi.org/10.1101/2023.07.07.548113 doi: bioRxiv preprint GCaMP6s responses and return latency at trial termination (left) nor at trigger zone entry (right).
(I) FLMM coefficient estimates plots of the return trial order effect and statistical significance at each trial time-point results for the photometric responses of pPVT D2(+) neurons for trial termination and trigger zone entry.No association between pPVT D2(+) GCaMP6s responses and trial order at trial termination (left) nor at trigger zone entry (right).
(J) Same as (H) but for photometric responses of pPVT D2(-) neuron.No association between pPVT D2(-) GCaMP6s responses and return latency at trial termination (left) nor at trigger zone entry (right).
(K) Same as (I) but for photometric responses of pPVT D2(-) neuron.No association between pPVT D2(-) GCaMP6s responses and trial order at trial termination (left) nor at trigger zone entry (right).
(L) Same as (H) but for photometric responses of aPVT D2(-) neuron.No association between aPVT D2(-) GCaMP6s responses and return latency at trial termination (left) nor at trigger zone entry (right).
(M) Same as (I) but for photometric responses of aPVT D2(-) neuron.No association between aPVT D2(-) GCaMP6s responses and trial order at trial termination (left) nor at trigger zone entry (right).
(N) FLMM coefficient estimates plots applying 'recording location' (i.e., aPVT or pPVT) as a covariate and showing statistical significance at each trial time-point results for the photometric responses of PVT D2(-) neurons for trial termination and trigger zone entry.No statistically significant differences between aPVT D2(-) GCaMP6s responses and pPVT D2(-) GCaMP6s responses at trial termination (left) nor at trigger zone entry (right).
(O) FLMM coefficient estimates plots of the approach latency effect and statistical significance at each trial time-point results for the photometric responses of pPVT D2(+) terminals for cue presentation and reward zone entry.Left: No association between pPVT D2(+) terminal responses and approach latency at cue presentation.Right: Plot showing a negative association between pPVT D2(+) terminal responses and approach latency before reward zone entry.
(P) FLMM coefficient estimates plots of the approach trial order effect and statistical significance at each trial time-point results for the photometric responses of pPVT D2(+) terminals for cue presentation and reward zone entry.Left: No association between pPVT D2(+) terminal responses and trial order at cue presentation.Right: Plot showing a negative association between pPVT D2(+) terminal responses and trial order approximately 1 sec after reward zone entry.
(Q) Same as (O) but for photometric responses of aPVT D2(-) terminals.Left: No association between aPVT D2(-) terminal responses and approach latency at cue presentation.Right: Plot showing a positive association between aPVT D2(-) terminal responses and approach latency before reward zone entry.
(R) Same as (P) but for photometric responses of aPVT D2(-) terminals.No association between aPVT D2(-) terminal responses and trial order at cue presentation (left) nor at reward zone entry (right).
105 and is also made available for use under a CC0 license.
(which was not certified by peer review) is the author/funder.This article is a US Government work.It is not subject to copyright under 17 USC The copyright holder for this preprint this version posted January 21, 2024.; https://doi.org/10.1101/2023.07.07.548113 doi: bioRxiv preprint neurons during cue presentation grouped by approach latency blocks.Right: AUC quantifications of GCaMP6s activity 105 and is also made available for use under a CC0 license.(whichwas not certified by peer review) is the author/funder.This article is a US Government work.It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.(whichwas not certified by peer review) is the author/funder.This article is a US Government work.It is not subject to copyright under 17 USC