Conditioning‐ and reward‐related dendritic and presynaptic plasticity of nucleus accumbens neurons in male and female sign‐tracker rats

• Published in: The European journal of neuroscience 2024-10, Vol.60 (7), p.5694-5717
• Main Authors: Colom, Morgane, Kraev, Igor, Stramek, Agata K., Loza, Iwona B., Rostron, Claire L., Heath, Christopher J., Dommett, Eleanor J., Singer, Bryan F.
• Format: Article
• Language: English
• Subjects: Animal models; Dendritic plasticity; Dendritic spines; Dopamine receptors; Estrus cycle; Females; Males; motivation; Neurobiology; Neuroplasticity; Neurosciences; Neurotransmission; Nucleus accumbens; Phenotypes; Presynaptic plasticity; rat; Reinforcement; sign‐tracking; synaptic plasticity; Synaptophysin
• ISSN: 0953-816X; 1460-9568; 1460-9568
• DOI: 10.1111/ejn.16513

For a subset of individuals known as sign‐trackers, discrete Pavlovian cues associated with rewarding stimuli can acquire incentive properties and exert control over behaviour. Because responsiveness to cues is a feature of various neuropsychiatric conditions, rodent models of sign‐tracking may prove useful for exploring the neurobiology of individual variation in psychiatric vulnerabilities. Converging evidence points towards the involvement of dopaminergic neurotransmission in the nucleus accumbens core (NAc) in the development of sign‐tracking, yet whether this phenotype is associated with specific accumbal postsynaptic properties is unknown. Here, we examined dendritic spine structural organisation, as well as presynaptic and postsynaptic markers of activity, in the NAc core of male and female rats following a Pavlovian‐conditioned approach procedure. In contrast to our prediction that cue re‐exposure would increase spine density, experiencing the discrete lever‐cue without reward delivery resulted in lower spine density than control rats for which the lever was unpaired with reward during training; this effect was tempered in the most robust sign‐trackers. Interestingly, this same behavioural test (lever presentation without reward) resulted in increased levels of a marker of presynaptic activity (synaptophysin), and this effect was greatest in female rats. Whilst some behavioural differences were observed in females during initial Pavlovian training, final conditioning scores did not differ from males and were unaffected by the oestrous cycle. This work provides novel insights into how conditioning impacts the neuronal plasticity of the NAc core, whilst highlighting the importance of studying the behaviour and neurobiology of both male and female rats. When attributed with motivational salience, reward‐predictive stimuli can drive behaviour and contribute to maladaptive responses. We examined whether variation in conditioned behaviours is associated with specific dendritic spine features and markers of pre‐ and post‐synaptic activity in the nucleus accumbens core of male and female rats. Data suggest that neuronal plasticity varies across individuals and is impacted by changes in reward availability during cue re‐exposure.