4.3. Ventral pallidum (VP)
The VP has received less attention than the VTA and the NAcc, but also
plays an important role in reward and reinforcement. The VP is the
primary output structure for mesolimbic reward circuitry. It is heavily
innervated by the GABAergic medium spiny neurons in the NAcc (Creed et
al. 2016; Ho and Berridge 2013; Kupchik et al. 2015; Root et al. 2015),
and projects back to the VTA and to several areas involved in the
regulation of movement (Root et al. 2015; Zahm 2000). Due to these
connectivity patterns, the VP is thought to be a primary hub where
motivational output from the NAcc is translated into appetitive behavior
(Smith et al. 2009); however, there is also evidence for bi-directional
communication between the NAcc and VP, as cue responses in the VP
sometimes precede and drive those in the NAcc (Chang et al. 2018;
Richard et al. 2016).
The VP is a heterogeneous structure, with rostral-caudal differences in
cell morphology and connectivity patterns (Kupchik and Kalivas 2013;
Root et al. 2015; Zahm 2000). For example, there are topographic
differences in projection patterns, with the anterior VP receiving
projections from the NAcc shell and the posterior VP receiving
projections from the NAcc core (Kupchik et al. 2015; Root et al. 2015).
The functional differences between anterior and posterior regions are
not well understood; however, some studies have found that they play
different roles in modulating reward-related behavior (Root et al. 2010;
Root et al. 2013), and have even been shown to have opposite effects on
hedonic responses to food reward (Smith and Berridge 2007; Smith et al.
2009).
Several studies have shown that neurons in the caudal VP respond to food
cues, with the magnitude of the response reflecting the strength of the
cue’s motivational impact (Avila and Lin 2014a, b; Smith et al. 2011;
Tachibana and Hikosaka 2012; Tindell et al. 2005; Tindell et al. 2006).
The VP has also been shown to specifically encode the incentive value of
a cue in a way that can be experimentally dissociated from reward
prediction (Smith et al. 2011; Tindell et al. 2005; Zhang et al. 2009).
For example, chemogenetic inactivation of the VP can impair the
acquisition (but not expression) of sign-tracking behavior, while
leaving goal-tracking unaffected (Chang et al. 2015). Importantly, the
VP is the only structure where differences in single-unit neural
activity have been documented between STs and GTs. In two previous
studies, STs have shown sustained changes in neural activity during
exposure to the lever cue that are greater, in terms of proportion of
responsive cells and the magnitude of responses, than that of GTs
(Ahrens et al. 2016a; Ahrens et al. 2018). The heightened VP activity in
STs was specifically evoked by the lever cue. When the same animals were
trained with a tone cue that predicted identical reward, but did not
support the attribution of incentive salience, the tone did not elicit
the robust changes in neural activity that were seen with the lever.
Therefore, not only does the VP reflects individual differences in
motivational tendencies, it tracks dynamic changes in incentive value of
cues as they change from trial to trial within a single animal (Ahrens
et al. 2018).
Few studies have specifically focused on the role of the VP during
sleep; however, the VP has been examined as part of the larger basal
forebrain region, which has been shown to play a very important role in
mediating both sleep and waking states (Jones 2017; Yang et al. 2017).
The basal forebrain describes a large area that encompasses the VP in
addition to other subcortical structures, such as the medial septum, bed
nucleus of the stria terminalis, substantia innominata, magnocellular
preoptic nucleus, and extended amygdala (Yang et al. 2017). The basal
forebrain contains a mix of cholinergic, glutamatergic, and GABAergic
cells that co-express different calcium-binding proteins. Among these
cell types four different functional activity patterns have been
identified. The most common type (~50%) are
cortically-projecting cells that show maximal firing during waking and
REM sleep, but not NREM sleep (Jones 2017), and when optogenetically
stimulated produces a rapid desynchronization of EEG and an increase in
wakefulness (Irmak and de Lecea 2014; Xu et al. 2015). The cholinergic
neurons almost exclusively fall in this wake-promoting category (Lee et
al. 2005), as do most glutamatergic neurons and some
parvalbumin-positive GABAergic neurons (Hassani et al. 2009). A second
type (~20%) are sleep-active, meaning they respond more
during NREM sleep than during active brain states. Most these neurons
are somatostatin-positive GABAergic neurons, with some glutamatergic
neurons, and they project primarily to the prefrontal cortex (Hassani et
al. 2009; Xu et al. 2015). The third type is relatively infrequent
(~10%) and are glutamatergic neurons that respond
maximally during waking. The fourth type (~20%) is
maximally responsive during REM sleep, but not waking. These are a mix
of GABAergic and glutamatergic cells that project primarily to the
posterior hypothalamus (Jones 2017). Although basal forebrain neurons
have been well characterized in the context of sleep and wakefulness, it
is not known whether there are individual differences in the composition
or function of these different cell types. It is also not known whether
the VP itself shares all of the same characteristics as this larger
basal forebrain region. Finally, further research is needed to determine
what role the VP plays (if any) on the ability of sleep to alter reward
seeking behavior.