TABLE 1.
Summary of the principal studies directly investigating thalamo = > accumbens projections in various motivated behaviors.
| References | Projections | Behaviors | Methods | Results | |
| Homeostatic and reward-seeking behaviors | Labouèbe et al., 2016 | PVT (Slc2a2) = > NAc | Sucrose-seeking | Optogenetic stimulation (terminals) | ↑ Motivated sucrose seeking |
| Do-Monte et al., 2017 | aPVT = > NAc (mainly shell) | Sucrose-seeking | Optogenetic inhibition (terminals) | ↑ Sucrose-seeking during reward omission | |
| Optogenetic stimulation (terminals) | ↓ Sucrose-seeking | ||||
| RTPP | Optogenetic stimulation (terminals) | Behavioral aversion | |||
| Cheng et al., 2018 | aPVT = > NAc | Novelty-suppressed feeding task | Optogenetic stimulation (terminals) | ↑ Feeding | |
| Ren et al., 2018 | PVT = > NAc | Sleep | Optogenetic stimulation (terminals) | ↑ Transitions from sleep to wakefulness | |
| Chemogenetic inhibition (cell bodies) | ↓ Wakefulness | ||||
| Meffre et al., 2019 | pPVT = > NAc core | Sucrose-seeking | Optogenetic stimulation (terminals) | ↑ NAc core neuronal responses to reward-predictive cues in sated animals | |
| Otis et al., 2019 | PVT = > NAc | Pavlovian conditioning | In vivo two-photon calcium imaging of PVT neurons projecting to the NAc | Inhibitory responses to reward-predictive cues. | |
| Lafferty et al., 2020 | PVT = > NAc shell | Operant task with cued periods of reward unavailability | Optogenetic inhibition (cell bodies or terminals) | ↑ Unproductive reward seeking | |
| Operant task without periods of reward unavailability | Chemogenetic activation (cell bodies) | ↓ Reward-seeking | |||
| RTPP | Optogenetic stimulation (terminals) | High variability | |||
| Self-stimulation | Optogenetic stimulation (terminals) | Reinforcing | |||
| Christoffel et al., 2021 | aPVT = > NAc | Limited-access high fat exposure | Optogenetic stimulation (terminals) | ↑ High fat intake during acquisition period | |
| Optogenetic inhibition (terminals) | ↓ High fat intake during acquisition and expression periods | ||||
| Chemogenetic inhibition (cell bodies) | ↓ High fat intake during expression period | ||||
| Optogenetic stimulation and brain slice electrophysiology | ↑ AMPAR/NMDAR ratio at aPVT = > D1R-MSNs synapses | ||||
| Optical LTD induction protocol in vivo | ↓ High fat intake after optical LTD | ||||
| High fat CPP | Optogenetic inhibition (terminals) | ↓ High fat paired chamber preference | |||
| Operant task: progressive ratio (high fat pellets) | Chemogenetic inhibition (cell bodies) | ↓ Breakpoint | |||
| Engelke et al., 2021 | aPVT = > NAc | Conflict test (food and predator odor) | Chemogenetic inhibition (cell bodies) | ↓ Defensive responses ↑ Food-seeking behavior | |
| aPVTCRF = > NAc shell | Conflict test (food and predator odor) | Optogenetic stimulation (terminals) | ↓ Food-seeking | ||
| RTPP | Optogenetic stimulation (terminals) | Behavioral aversion | |||
| Drug experience and addiction | Joffe and Grueter., 2016 | Midline thalamic nuclei = > NAc core | Cocaine exposure followed by 2 weeks of abstinence | Optogenetic stimulation and brain slice electrophysiology | ↑ AMPAR and NMDAR function at D1R-MSNs ↑ Silent synapses at D2R-MSNs |
| Neumann et al., 2016 | PVT = > NAc shell | Cocaine self-administration | Disruption of synaptic transmission (tetanus toxin) | ↓ Acquisition of cocaine self-administration | |
| 1–2 days of withdrawal after cocaine self-admin. | Optogenetic stimulation and brain slice electrophysiology | ↑ Silent synapses ↑ Presynaptic release probability | |||
| 45 days of withdrawal after cocaine self-admin. | ↑ Presynaptic release probability | ||||
| Zhu et al., 2016 | PVT = > NAc medial shell | RTPP | Optogenetic stimulation (terminals) | Behavioral aversion | |
| Naloxone-precipitated opiate withdrawal | Optogenetic inhibition (terminals) or optogenetic long term depression protocol (terminals) | ↓ Somatic signs of opiate dependence ↓ Place-aversion | |||
| CPA induced by spontaneous opiate withdrawal/mild footshock/LiCl intraperitoneal injection | Chemogenetic inhibition (terminals) before CPA conditioning | ↓ Place-aversion | |||
| PVT = > NAc | Chronic morphine exposure | Optogenetic stimulation and brain slice electrophysiology | ↑ AMPAR/NMDAR ratio in D2R-MSNs | ||
| Wunsch et al., 2017 | Anterior midline and intralaminar thalamic nuclei = > NAc | Reinstatement of cocaine self-administration after extinction | Chemogenetic inhibition (cell bodies) | ↑ Cue-induced reinstatement ↓ Drug-primed reinstatement | |
| Keyes et al., 2020 | PVT = > NAc | Morphine CPP | Chemogenetic inhibition (terminals) or optogenetic inhibition (terminals) during CPP expression | ↓ Retrieval of opiate associated memories (persistently) ↓ Morphine-primed relapse | |
| Chisholm et al., 2021 | PVT = > NAc shell | Relapse after heroin self-administration followed by withdrawal and food restriction | Chemogenetic activation (terminals) | ↓ Heroin seeking in food-restricted rats |
All methods presented here directly targeted the thalamic neurons projecting to the NAc, either by retrograde transport of viral tools from the NAc to the thalamus (cell bodies), or by local manipulation of the thalamic projections in the NAc (terminals). CPA, conditioned place aversion; CPP, conditioned place preference; CRF, corticotrophin-releasing factor; LTD, long-term depression; NAc, nucleus accumbens; PVT, paraventricular thalamus; aPVT, anterior paraventricular thalamus; pPVT, posterior paraventricular thalamus; RTPP, real-time place preference. Arrow up means increased. Arrow down means decreased.