Distinct Encoding of Reward and Aversion by Peptidergic BNST Inputs to the VTA

Abstract

Neuropeptides play an important role in modulating mesolimbic system function. However, while synaptic inputs to the ventral tegmental area (VTA) have been extensively mapped, the sources of many neuropeptides are not well resolved. Here, we mapped the anatomical locations of three neuropeptide inputs to the VTA: neurotensin (NTS), corticotrophin releasing factor (CRF), and neurokinin B (NkB). Among numerous labeled inputs we identified the bed nucleus of the stria terminalis (BNST) as a major source of all three peptides, containing similar numbers of NTS, CRF, and NkB VTA projection neurons. Approximately 50% of BNST to VTA inputs co-expressed two or more of the peptides examined. Consistent with this expression pattern, analysis of calcium dynamics in the terminals of these inputs in the VTA revealed both common and distinct patterns of activation during appetitive and aversive conditioning. These data demonstrate additional diversification of the mesolimbic dopamine system through partially overlapping neuropeptidergic inputs.

Distinct dynamics and intrinsic properties in ventral tegmental area populations mediate reward association and motivation

“…Using this approach, we sought to resolve how and when these VTA dopaminergic subpopulations encode task-related features during an appetitive instrumental conditioning task. To achieve this, we monitored neural activity in subpopulations of dopamine neurons that have been shown to differentially innervate the NAc core ( Crhr1 VTA cells) or NAc shell ( Cck VTA cells) during a cued reinstatement paradigm ( Figure 1A-1B ; Nugent et al, 2017; Soden et al, 2022). We also monitored neural activity dynamics in VTA dopamine neurons as a whole (DAT VTA ) and in VTA GABAergic neurons (Vgat VTA ).…”

Whole‐brain mapping of monosynaptic afferent inputs to the CRH neurons in the medial prefrontal cortex of mice

“…However, compared to previous reports, there were some inconsistencies in our results. For instance, the ventral tegmental area (VTA), as one of the main parts in midbrain, played an important role in motivation, reward, and addiction (Soden et al., 2022). The paraventricular nucleus of the thalamus (PVT) is known for its regulation of stress, anxiety, and drug abuse, and it has been shown to project to the mPFC (Pliota et al., 2020).…”

CaMKIIa+ neurons in the bed nucleus of the stria terminalis modulate pace of natural reward seeking depending on internal state

“…In addition, as the BNST is closely connected to many brain regions including several cortical regions, the hypothalamus, amygdala, periaqueductal grey, ventral tegmental area and nucleus accumbens (Dong and Swanson 2004; Lebow and Chen 2016; Stamatakis et al 2014), it is reasonable to assume that the BNST is not acting alone, but closely collaborates with other brain areas to regulate behavioral responses to different natural rewards. As mentioned previously, the BNST modulates reward and aversion through its projection to the ventral tegmental area (Jennings et al 2013b; Soden et al 2022), while connections with the amygdala, medial prefrontal cortex, and hypothalamus are involved in processing mood and arousal states and monitoring of food and fluid intake (Davis et al 2010; Dong et al 2001; Dong and Swanson 2004; Hammack et al 2009; Radley and Sawchenko 2011; Rodriguez-Romaguera et al 2020). Future research should reveal to what extent these projecting brain areas are involved in sexual behavior and sucrose consumption, and to what extent the underlying neurobiological mechanisms converge or overlap.…”

“…The bed nucleus of the stria terminalis (BNST) is implicated in stress, anxiety, drug seeking, addiction, and socio-sexual behavior (reviewed in: (Flanigan and Kash 2022; Lebow and Chen 2016)). Through its projection to the ventral tegmental area, the BNST modulates reward and aversion (Jennings et al 2013b; Soden et al 2022), while connections with the amygdala, medial prefrontal cortex, and hypothalamus are involved in processing mood and arousal states, and monitoring of food and fluid intake (Davis et al 2010; Dong et al 2001; Dong and Swanson 2004; Hammack et al 2009; Radley and Sawchenko 2011; Rodriguez-Romaguera et al 2020). Consequently, it has been proposed that the BNST has a function in valence surveillance, meaning that it weighs various types of information such as environmental context, historical experience and internal state, in order to guide an appropriate response towards a stimulus (Lebow and Chen 2016).…”