4.2. Hippocampus (HPC)
The hippocampus is known to play a critical role in learning, as well as the consolidation of memories during sleep (Dudai 2004). Network connectivity between the NAcc and the hippocampus may also play an important role in mediating the effects of SD on reward-related behavior and motivation. The encoding of memory by the hippocampus depends on the reactivation of specific experience-related neural firing sequences during NREM sleep, and if this neuronal replay is interrupted by sleep loss it impairs the subsequent recall of spatial and contextual memories (Chen and Wilson 2017). A similar process of spontaneous replay has been observed in the ventral striatum during NREM sleep following performance of a reward-related task (Ahmed et al. 2008; Lansink et al. 2008; Pennartz et al. 2004), and this reactivation is critical for the encoding of reward-related memories, such as the spatial location of food reward (Lansink et al. 2012). Replay sequences in the NAcc can be triggered by sharp wave ripples in the hippocampus (Singer and Frank 2009) and replay in the NAcc is dominated by pairs of neurons in which hippocampal “place” cells fire immediately before the reward-related NAcc neuron (Lansink et al. 2009). Therefore, joint reactivation of hippocampal and NAcc firing patterns represents an important mechanism for consolidation of place-reward associations, and may be particularly vulnerable to disruption by SD.
Reward encoding can also take place within the hippocampus itself. Place cell firing fields accumulate near goal locations (Hollup et al. 2001), and there are dedicated populations of neurons in the HPC that specifically encode proximity to reward (Gauthier and Tank 2018). The ventral region of the HPC plays a particularly important role in reward processing. The ventral HPC sends prominent glutamatergic projections to the NAcc which are responsible for carrying spatial information to the NAcc and are critical for linking reward learning with contextual information (Britt et al. 2012; Lansink et al. 2008; Lansink et al. 2009). For example, the learning of context-drug associations selectively strengthens the connection between ventral HPC place cells and medium spiny neurons in the NAcc (Sjulson et al. 2018), and disruption of this pathway by inactivation of the ventral (but not dorsal) HPC impairs the retrieval of contextual reward memory (Riaz et al. 2017).
The ventral HPC also plays an important role in sign-tracking. One study found that lesions of the ventral HPC, but not dorsal HPC, impaired the initial learning of a sign-tracking response (Fitzpatrick et al. 2016a). In another study, STs were found to have elevated myo-inositol (a marker of glial activity and proliferation) in the ventral (but not dorsal) HPC relative to GTs (Fitzpatrick et al. 2016b). Therefore, individual differences in the HPC inputs to the NAcc could be a contributing factor in the development of ST versus GT behavioral responses. It is possible that differences in hippocampal ripple-triggered activity in the NAcc during sleep may play a critical role in how some individuals develop stronger incentive motivational associations with reward cues than others. Examination of this connection in the ST/GT model would be a critical first step in understanding the importance of the HPC in the attribution of incentive salience to cues.