Reward drives motivated behaviours and is essential for survival, and therefore there is strong evolutionary pressure to retain contextual information about rewarding stimuli. This drive may be abnormally strong, such as in addiction, or weak, such as in depression, in which anhedonia (loss of pleasure in response to rewarding stimuli) is a prominent symptom. Hippocampal input to the shell of the nucleus accumbens (NAc) is important for driving NAc activity1,2 and activity-dependent modulation of the strength of this input may contribute to the proper regulation of goal-directed behaviours. However, there have been few robust descriptions of the mechanisms that underlie the induction or expression of long-term potentiation (LTP) at these synapses, and there is, to our knowledge, no evidence about whether such plasticity contributes to reward-related behaviour. Here we show that high-frequency activity induces LTP at hippocampus–NAc synapses in mice via canonical, but dopamine-independent, mechanisms. The induction of LTP at this synapse in vivo drives conditioned place preference, and activity at this synapse is required for conditioned place preference in response to a natural reward. Conversely, chronic stress, which induces anhedonia, decreases the strength of this synapse and impairs LTP, whereas antidepressant treatment is accompanied by a reversal of these stress-induced changes. We conclude that hippocampus–NAc synapses show activity-dependent plasticity and suggest that their strength may be critical for contextual reward behaviour.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Datasets are available from the corresponding author upon request.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
We thank B. Mathur for D1–tdtomato mice; K. Deisseroth for permission to use the viral optogenetic constructs; the University of Maryland School of Medicine Center for Innovative Biomedical Resources, Confocal Microscopy Core for use of the confocal microscopes; the NIMH Chemical Synthesis and Drug Supply Program for supplying fluoxetine, and T. Gould, T. Blanpied, and T. Bale for suggestions and advice. This work was supported by R01MH086828 (S.M.T.), T32 NS007375 (T.A.L.), a NARSAD Young Investigator Award (T.A.L.), the Whitehall Foundation 2017-12-54 (M.C.C. and J.R.T.), and R01MH106500 (M.K.L. and T.C.F.).
Nature thanks J. Dani, C. McClung and the other anonymous reviewer(s) for their contribution to the peer review of this work.