4.6. Paraventricular nucleus of the thalamus (PVT).
The PVT is a thalamic midline structure with numerous connections to
cortical, limbic, and motor structures (Kelley et al. 2005; Li and
Kirouac 2012), including dense projections to the NAcc, prelimbic and
infralimbic cortices, and amygdala (Vertes and Hoover 2008). Recent
studies have found that the PVT may be one of the key structures
mediating incentive versus predictive cue responses seen in STs and GTs.
Under normal conditions the PVT appears to suppress the attribution of
incentive salience to cues and plays a role in preventing GTs from
expressing attraction to cues. For example, disruption of PVT activity
has been shown to increase sign-tracking behavior and decrease
goal-tracking behavior, causing rats previously identified as GTs to
switch to sign-tracking (Haight et al. 2015). Furthermore, disruption of
the PVT increases cue-induced reinstatement of drug seeking in GTs to
the level normally seen in STs (Kuhn et al. 2017). A recent
dual-labeling study (c-fos and flourogold) found that in both STs and
GTs a food-paired cue activated the projection from the prelimbic cortex
to the PVT, suggesting that this pathway mediates the predictive value
of the cue, which both STs and GTs experience equally. However, in STs,
the cues also activated subcortical pathways from the hypothalamus and
amygdala to the PVT, as well as projections from the PVT to the ventral
striatum, suggesting that these connections are involved in processing
the incentive value of a cue. Therefore, the prelimbic-to-PVT pathway is
hypothesized to be part of an inhibitory mechanism by which GTs exert
greater cortical “top-down” control over motivated behavior and react
primarily to the predictive value of a cue. The lack of this inhibition
causes STs to act more on “bottom-up” emotional impulses driven by
subcortical circuitry (Haight et al. 2017).
In addition to its prominent role in incentive motivation, the PVT is
also ideally situated to play an important role in modulating sleep-wake
states. The PVT receives synaptic inputs from, and projects back to, the
suprachiasmatic nucleus (SCN), which is the master clock that regulates
circadian rhythms in mammals (Alamilla et al. 2015; Colavito et al.
2015; Moga et al. 1995; Peng and Bentivoglio 2004; Vertes and Hoover
2008). Through its dense projections to limbic areas, the PVT can relay
information about circadian rhythms from the SCN to the NAcc, amygdala,
infralimbic and prelimbic cortices (Vertes and Hoover 2008). In
addition, axon terminals of SCN fibers terminate on PVT neurons
projecting to the amygdala (Peng and Bentivoglio 2004). Many of these
connections are reciprocal, and since the PVT projects back to the SCN
it can mediate the ability of behavioral arousal and attentive states to
alter circadian rhythms. For example, inputs from the PVT can shift
membrane potential in SCN neurons and make them more responsive to
external light cues transmitted through the retinohypothalamic tract
(Alamilla et al. 2015). Therefore, the PVT is in an ideal position to
relay information about circadian timing from the SCN to brain regions
involved in motivation aspects of behavior, and to also provide
regulatory feedback to the SCN.
There is a bidirectional relationship between circadian rhythms and
reward-related behavior, and given that circadian rhythms play such an
integral role in regulating sleep, it is likely that individual traits
related to circadian mechanisms play a role in the interaction between
sleep and substance abuse (DePoy et al. 2017). Polymorphisms in
circadian clock genes (including per1 and per2) have been shown to
increase alcohol consumption in rodents (Dong et al. 2011; Spanagel et
al. 2005), and in humans have been associated with cocaine addiction and
reduced dopamine D2 receptor expression in the striatum (Shumay et al.
2012). The link between circadian rhythms and addictive behavior is
complicated by the fact that exposure to alcohol, drugs of abuse, and
food reward in some cases, can cause disruption or entrainment of
circadian timing (Hasler et al. 2012; Webb 2017). Therefore, as with
other aspects of sleep, it is not yet known which features of circadian
rhythms represent underlying predisposing traits, and which results from
drug exposure or environmental factors.